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Sample records for chronically infected mice

  1. Development of an in vivo model of Chlamydia abortus chronic infection in mice overexpressing IL-10.

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    Del Río, Laura; Murcia, Antonio; Buendía, Antonio J; Álvarez, Daniel; Ortega, Nieves; Navarro, José A; Salinas, Jesús; Caro, María Rosa

    2018-01-01

    Chlamydia abortus, like other members of the family Chlamydiaceae, have a unique intracellular developmental cycle that is characterized by its chronic nature. Infection of a flock can remain undetected for months, until abortion occurs the following reproductive season but, to date, neither the location nor the mechanisms that maintain this latent phase are fully understood. Studies have shown that IL-10 produced as a response to certain micro-organisms sustains the intracellular survival of pathogens and increases host susceptibility to chlamydial infections. In order to induce a sustained infection C. abortus, transgenic mice that constitutively express IL-10 were infected and the immunological mechanisms that maintain infection in these mice were compared with the mechanisms of a resistant wild-type mouse strain. Viable bacteria could be detected in different tissues of transgenic mice up to 28 days after infection, as analysed by bacterial isolation and immunohistochemistry. Chronic infection in these mice was associated with an impaired recruitment of macrophages, decreased iNOS activity at the site of infection and a more diffuse distribution of inflammatory cells in the liver. This murine model can be of great help for understanding the immunological and bacterial mechanisms that lead to chronic chlamydial infections. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Persistent Coxiella burnetii infection in mice overexpressing IL-10: an efficient model for chronic Q fever pathogenesis.

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    Soraya Meghari

    2008-02-01

    Full Text Available Interleukin (IL-10 increases host susceptibility to microorganisms and is involved in intracellular persistence of bacterial pathogens. IL-10 is associated with chronic Q fever, an infectious disease due to the intracellular bacterium Coxiella burnetii. Nevertheless, accurate animal models of chronic C. burnetii infection are lacking. Transgenic mice constitutively expressing IL-10 in macrophages were infected with C. burnetti by intraperitoneal and intratracheal routes and infection was analyzed through real-time PCR and antibody production. Transgenic mice exhibited sustained tissue infection and strong antibody response in contrast to wild-type mice; thus, bacterial persistence was IL-10-dependent as in chronic Q fever. The number of granulomas was low in spleen and liver of transgenic mice infected through the intraperitoneal route, as in patients with chronic Q fever. Macrophages from transgenic mice were unable to kill C. burnetii. C. burnetii-stimulated macrophages were characterized by non-microbicidal transcriptional program consisting of increased expression of arginase-1, mannose receptor, and Ym1/2, in contrast to wild-type macrophages in which expression of inducible NO synthase and inflammatory cytokines was increased. In vivo results emphasized macrophage data. In spleen and liver of transgenic mice infected with C. burnetii by the intraperitoneal route, the expression of arginase-1 was increased while microbicidal pathway consisting of IL-12p40, IL-23p19, and inducible NO synthase was depressed. The overexpression of IL-10 in macrophages prevents anti-infectious competence of host, including the ability to mount granulomatous response and microbicidal pathway in tissues. To our knowledge, this is the first efficient model for chronic Q fever pathogenesis.

  3. Environmental Burkholderia cenocepacia Strain Enhances Fitness by Serial Passages during Long-Term Chronic Airways Infection in Mice

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    Alessandra Bragonzi

    2017-11-01

    Full Text Available Burkholderia cenocepacia is an important opportunistic pathogen in cystic fibrosis (CF patients, and has also been isolated from natural environments. In previous work, we explored the virulence and pathogenic potential of environmental B. cenocepacia strains and demonstrated that they do not differ from clinical strains in some pathogenic traits. Here, we investigated the ability of the environmental B. cenocepacia Mex1 strain, isolated from the maize rhizosphere, to persist and increase its virulence after serial passages in a mouse model of chronic infection. B. cenocepacia Mex1 strain, belonging to the recA lineage IIIA, was embedded in agar beads and challenged into the lung of C57Bl/6 mice. The mice were sacrificed after 28 days from infection and their lungs were tested for bacterial loads. Agar beads containing the pool of B. cenocepacia colonies from the four sequential passages were used to infect the mice. The environmental B. cenocepacia strain showed a low incidence of chronic infection after the first passage; after the second, third and fourth passages in mice, its ability to establish chronic infection increased significantly and progressively up to 100%. Colonial morphology analysis and genetic profiling of the Mex1-derived clones recovered after the fourth passage from infected mice revealed that they were indistinguishable from the challenged strain both at phenotypic and genetic level. By testing the virulence of single clones in the Galleria mellonella infection model, we found that two Mex1-derived clones significantly increased their pathogenicity compared to the parental Mex1 strain and behaved similarly to the clinical and epidemic B. cenocepacia LMG16656T. Our findings suggest that serial passages of the environmental B. cenocepacia Mex1 strain in mice resulted in an increased ability to determine chronic lung infection and the appearance of clonal variants with increased virulence in non-vertebrate hosts.

  4. Chronic Trichuris muris infection causes neoplastic change in the intestine and exacerbates tumour formation in APC min/+ mice.

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    Kelly S Hayes

    2017-06-01

    Full Text Available Incidences of infection-related cancers are on the rise in developing countries where the prevalence of intestinal nematode worm infections are also high. Trichuris muris (T. muris is a murine gut-dwelling nematode that is the direct model for human T. trichiura, one of the major soil-transmitted helminth infections of humans. In order to assess whether chronic infection with T. muris does indeed influence the development of cancer hallmarks, both wild type mice and colon cancer model (APC min/+ mice were infected with this parasite. Parasite infection in wild type mice led to the development of neoplastic change similar to that seen in mice that had been treated with the carcinogen azoxymethane. Additionally, both chronic and acute infection in the APCmin/+ mice led to an enhanced tumour development that was distinct to the site of infection suggesting systemic control. By blocking the parasite induced T regulatory response in these mice, the increase in the number of tumours following infection was abrogated. Thus T. muris infection alone causes an increase in gut pathologies that are known to be markers of cancer but also increases the incidence of tumour formation in a colon cancer model. The influence of parasitic worm infection on the development of cancer may therefore be significant.

  5. Progression of chronic pulmonary tuberculosis in mice intravenously infected with ethambutol resistant Mycobacterium tuberculosis

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    Srivastava S

    2008-01-01

    Full Text Available Purpose: Ethambutol (EMB is an important first line drug, however little information on its molecular mechanism of resistance and pathogenicity of resistant isolates is available. Present work was designed to study virulence of the EMB resistant M. tuberculosis strains and the host responses in-vivo on infection of EMB resistant M. tuberculosis using Balb/c mouse model of infection. Methods: Three groups of Balb/c mice (female, age 4-6 wk; 21 mice in each group were infected intravenously with 106 CFU of M. tuberculosis H37Rv and two EMB resistant clinical isolates. Age and sex matched control animals were mock inoculated with Middlebrook 7H9 broth alone. At 10, 20, 30, 40, 50, 60, and 70 days post-infection three animals from each group were sacrificed by cervical dislocation and lung tissue was collected for further analysis. Results: Infection with EMB resistant M. tuberculosis led to progressive and chronic disease with significantly high bacillary load (p=0.02. Massive infiltration and exacerbated lung pathology with increased expression of IFN-γ and TNF-α was observed in lungs of mice infected with EMB resistant strains. The present study suggests that infection with EMB resistant M. tuberculosis leads to chronic infection with subsequent loss of lung function, bacterial persistence with elevated expression of TNF-α resulting in increased lung pathology. Conclusion: These findings highlight that EMB resistant M. tuberculosis regulates host immune response differentially and its pathogenicity is different from drug sensitive strains of M. tuberculosis.

  6. Toxoplasma gondii Actively Inhibits Neuronal Function in Chronically Infected Mice

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    Haroon, Fahad; Händel, Ulrike; Angenstein, Frank; Goldschmidt, Jürgen; Kreutzmann, Peter; Lison, Holger; Fischer, Klaus-Dieter; Scheich, Henning; Wetzel, Wolfram; Schlüter, Dirk; Budinger, Eike

    2012-01-01

    Upon infection with the obligate intracellular parasite Toxoplasma gondii, fast replicating tachyzoites infect a broad spectrum of host cells including neurons. Under the pressure of the immune response, tachyzoites convert into slow-replicating bradyzoites, which persist as cysts in neurons. Currently, it is unclear whether T. gondii alters the functional activity of neurons, which may contribute to altered behaviour of T. gondii–infected mice and men. In the present study we demonstrate that upon oral infection with T. gondii cysts, chronically infected BALB/c mice lost over time their natural fear against cat urine which was paralleled by the persistence of the parasite in brain regions affecting behaviour and odor perception. Detailed immunohistochemistry showed that in infected neurons not only parasitic cysts but also the host cell cytoplasm and some axons stained positive for Toxoplasma antigen suggesting that parasitic proteins might directly interfere with neuronal function. In fact, in vitro live cell calcium (Ca2+) imaging studies revealed that tachyzoites actively manipulated Ca2+ signalling upon glutamate stimulation leading either to hyper- or hypo-responsive neurons. Experiments with the endoplasmatic reticulum Ca2+ uptake inhibitor thapsigargin indicate that tachyzoites deplete Ca2+ stores in the endoplasmatic reticulum. Furthermore in vivo studies revealed that the activity-dependent uptake of the potassium analogue thallium was reduced in cyst harbouring neurons indicating their functional impairment. The percentage of non-functional neurons increased over time In conclusion, both bradyzoites and tachyzoites functionally silence infected neurons, which may significantly contribute to the altered behaviour of the host. PMID:22530040

  7. Toxoplasma gondii actively inhibits neuronal function in chronically infected mice.

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    Fahad Haroon

    Full Text Available Upon infection with the obligate intracellular parasite Toxoplasma gondii, fast replicating tachyzoites infect a broad spectrum of host cells including neurons. Under the pressure of the immune response, tachyzoites convert into slow-replicating bradyzoites, which persist as cysts in neurons. Currently, it is unclear whether T. gondii alters the functional activity of neurons, which may contribute to altered behaviour of T. gondii-infected mice and men. In the present study we demonstrate that upon oral infection with T. gondii cysts, chronically infected BALB/c mice lost over time their natural fear against cat urine which was paralleled by the persistence of the parasite in brain regions affecting behaviour and odor perception. Detailed immunohistochemistry showed that in infected neurons not only parasitic cysts but also the host cell cytoplasm and some axons stained positive for Toxoplasma antigen suggesting that parasitic proteins might directly interfere with neuronal function. In fact, in vitro live cell calcium (Ca(2+ imaging studies revealed that tachyzoites actively manipulated Ca(2+ signalling upon glutamate stimulation leading either to hyper- or hypo-responsive neurons. Experiments with the endoplasmatic reticulum Ca(2+ uptake inhibitor thapsigargin indicate that tachyzoites deplete Ca(2+ stores in the endoplasmatic reticulum. Furthermore in vivo studies revealed that the activity-dependent uptake of the potassium analogue thallium was reduced in cyst harbouring neurons indicating their functional impairment. The percentage of non-functional neurons increased over time In conclusion, both bradyzoites and tachyzoites functionally silence infected neurons, which may significantly contribute to the altered behaviour of the host.

  8. INFECTIOUS VIRUS-ANTIBODY COMPLEX IN THE BLOOD OF CHRONICALLY INFECTED MICE

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    Notkins, Abner Louis; Mahar, Suellen; Scheele, Christina; Goffman, Joel

    1966-01-01

    If viremic sera from mice chronically infected with lactic dehydrogenase virus (LDV) were first treated with ether or ultraviolet light to inactivate the infectious virus, neutralizing antibody could be demonstrated. Significant amounts of antibody, however, were not detected until the mice had been infected for about 2½ months and its presence did not result in the elimination of the chronic viremia. Virus isolated from sera containing neutralizing antibody was found to be relatively resistant to neutralization by anti-LDV. Further studies revealed that the resistant virus existed in the form of an infectious virus-antibody complex (sensitized virus). The presence of such a complex was demonstrated by the fact that the virus fraction which persisted after in vivo or in vitro exposure to mouse anti-LDV was readily neutralized by goat anti-mouse sera or goat anti-mouse γ-globulin, whereas virus that had not been previously exposed to mouse anti-LDV was completely resistant to neutralization by goat anti-mouse sera. These findings suggest that (a) sensitization may play an important role in the resistance and susceptibility of a virus to neutralization by antiviral antibody, and (b) an anti-γ-globulin may prove useful in neutralizing the resistant fraction and in demonstrating otherwise undetectable antiviral antibody. PMID:5944351

  9. Minocycline attenuates HIV-1 infection and suppresses chronic immune activation in humanized NOD/LtsZ-scidIL-2Rγnull mice

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    Singh, Maneesh; Singh, Pratibha; Vaira, Dolores; Amand, Mathieu; Rahmouni, Souad; Moutschen, Michel

    2014-01-01

    More than a quarter of a century of research has established chronic immune activation and dysfunctional T cells as central features of chronic HIV infection and subsequent immunodeficiency. Consequently, the search for a new immunomodulatory therapy that could reduce immune activation and improve T-cell function has been increased. However, the lack of small animal models for in vivo HIV study has hampered progress. In the current study, we have investigated a model of cord blood haematopoietic progenitor cells (CB-HPCs) -transplanted humanized NOD/LtsZ-scidIL-2Rγnull mice in which progression of HIV infection is associated with widespread chronic immune activation and inflammation. Indeed, HIV infection in humanized NSG mice caused up-regulation of several T-cell immune activation markers such as CD38, HLA-DR, CD69 and co-receptor CCR5. T-cell exhaustion markers PD-1 and CTLA-4 were found to be significantly up-regulated on T cells. Moreover, increased plasmatic levels of lipopolysaccharide, sCD14 and interleukin-10 were also observed in infected mice. Treatment with minocycline resulted in a significant decrease of expression of cellular and plasma immune activation markers, inhibition of HIV replication and improved T-cell counts in HIV-infected humanized NSG mice. The study demonstrates that minocycline could be an effective, low-cost adjunctive treatment to regulate chronic immune activation and replication of HIV. PMID:24409837

  10. Salmonella Typhimurium undergoes distinct genetic adaption during chronic infections of mice

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    Søndberg, Emilie; Jelsbak, Lotte

    2016-01-01

    Background Typhoid fever caused by Salmonella enterica serovar Typhi (S. Typhi) is a severe systemic human disease and endemic in regions of the world with poor drinking water quality and sewage treatment facilities. A significant number of patients become asymptomatic life-long carriers of S....... In the current study genetic adaptation during experimental chronic S. Typhimurium infections of mice, an established model of chronic typhoid fever, was probed as an approach for studying the molecular mechanisms of host-adaptation during long-term host-association. Results Individually sequence-tagged wild...

  11. Chronic Pseudomonas aeruginosa lung infection is more severe in Th2 responding BALB/c mice compared to Th1 responding C3H/HeN mice

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    Moser, C; Johansen, H K; Song, Z

    1997-01-01

    model of this infection was established in two strains of mice: C3H/HeN and BALB/c, generally known as Th1 and Th2 responders, respectively, which were challenged with alginate-embedded P. aeruginosa. Mortality was significantly lower in C3H/HeN compared to BALB/c mice (p ... was cleared more efficiently in C3H/HeN mice and significantly more C3H/HeN mice showed normal lung histopathology (p BALB/c mice (p ... from the two strains of mice, the interferon-(IFN-) gamma levels were higher, whereas IL-4 levels were lower in C3H/HeN mice than in BALB/c mice. The implications of these findings for CF patients with chronic P. aeruginosa lung infection are discussed....

  12. Phenotypic complementation of genetic immunodeficiency by chronic herpesvirus infection.

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    MacDuff, Donna A; Reese, Tiffany A; Kimmey, Jacqueline M; Weiss, Leslie A; Song, Christina; Zhang, Xin; Kambal, Amal; Duan, Erning; Carrero, Javier A; Boisson, Bertrand; Laplantine, Emmanuel; Israel, Alain; Picard, Capucine; Colonna, Marco; Edelson, Brian T; Sibley, L David; Stallings, Christina L; Casanova, Jean-Laurent; Iwai, Kazuhiro; Virgin, Herbert W

    2015-01-20

    Variation in the presentation of hereditary immunodeficiencies may be explained by genetic or environmental factors. Patients with mutations in HOIL1 (RBCK1) present with amylopectinosis-associated myopathy with or without hyper-inflammation and immunodeficiency. We report that barrier-raised HOIL-1-deficient mice exhibit amylopectin-like deposits in the myocardium but show minimal signs of hyper-inflammation. However, they show immunodeficiency upon acute infection with Listeria monocytogenes, Toxoplasma gondii or Citrobacter rodentium. Increased susceptibility to Listeria was due to HOIL-1 function in hematopoietic cells and macrophages in production of protective cytokines. In contrast, HOIL-1-deficient mice showed enhanced control of chronic Mycobacterium tuberculosis or murine γ-herpesvirus 68 (MHV68), and these infections conferred a hyper-inflammatory phenotype. Surprisingly, chronic infection with MHV68 complemented the immunodeficiency of HOIL-1, IL-6, Caspase-1 and Caspase-1;Caspase-11-deficient mice following Listeria infection. Thus chronic herpesvirus infection generates signs of auto-inflammation and complements genetic immunodeficiency in mutant mice, highlighting the importance of accounting for the virome in genotype-phenotype studies.

  13. Salmonella Typhimurium undergoes distinct genetic adaption during chronic infections of mice

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    Søndberg, Emilie; Jelsbak, Lotte

    2016-01-01

    Background Typhoid fever caused by Salmonella enterica serovar Typhi (S. Typhi) is a severe systemic human disease and endemic in regions of the world with poor drinking water quality and sewage treatment facilities. A significant number of patients become asymptomatic life-long carriers of S....... Typhi and serve as the reservoir for the disease. The specific mechanisms and adaptive strategies enabling S. Typhi to survive inside the host for extended periods are incompletely understood. Yet, elucidation of these processes is of major importance for improvement of therapeutic strategies...... been transmitted to the other two mice. Re-infection with this clone confirmed that it is superior to the wild type for intestinal colonisation. Conclusions During 4 to 6 weeks of chronic infections, S. Typhimurium acquired distinct SNPs in known regulators of metabolic and virulence genes. One SNP...

  14. Comparative efficacy of some quinolones and doxycycline against chronic infection of brucella melitensis 16M in balb/c mice

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    Safi, M.; Albalaa, B.; Mahmoud, N.H.; Mariri, A.A.

    2016-01-01

    This study was under taken to observe various treatment methods for brucellosis caused by Brucella melitensis . The effect of therapeutic regimens with ciprofloxacin, ofloxacin and levofloxacin alone or in combination with doxycycline was assessed against B. melitensis chronic infection using 200 mice. Doxycycline alone or in combination with ciprofloxacin was significantly found to reduce the infection till 135 days post-infection (p<0.0001). Moreover, doxycycline was more effective than ciprofloxacin and ofloxacin 135 days post-infection (p = 0.04 and p = 0.02, respectively). However, treatment with quinolone-doxycycline combinations revealed synergistic effects as they were able to reduce the splenic cell forming unit (CFU) from day 45 post-infection. Similarly, doxycycline treatment reduced the splenic colony forming unit (CFU) from day 90 post-infection. In conclusion, doxycycline seems to be the most effective agent against Brucella chronic infection. (author)

  15. Experimental toxoplasmosis in Balb/c mice. Prevention of vertical disease transmission by treatment and reproductive failure in chronic infection

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    B Fux

    2000-01-01

    Full Text Available In a study of congenital transmission during acute infection of Toxoplasma gondii, 23 pregnant Balb/c mice were inoculated orally with two cysts each of the P strain. Eight mice were inoculated 6-11 days after becoming pregnant (Group 1. Eight mice inoculated on the 10th-15th day of pregnancy (Group 2 were treated with 100 mg/kg/day of minocycline 48 h after inoculation. Seven mice inoculated on the 10th-15th day of pregnancy were not treated and served as a control (Group 3. Congenital transmission was evaluated through direct examination of the brains of the pups or by bioassay and serologic tests. Congenital transmission was observed in 20 (60.6% of the 33 pups of Group 1, in one (3.6% of the 28 pups of Group 2, and in 13 (54.2% of the 24 pups of Group 3. Forty-nine Balb/c mice were examined in the study of congenital transmission of T. gondii during chronic infection. The females showed reproductive problems during this phase of infection. It was observed accentuated hypertrophy of the endometrium and myometrium. Only two of the females gave birth. Our results demonstrate that Balb/c mice with acute toxoplasmosis can be used as a model for studies of congenital T. gondii infection. Our observations indicate the potential of this model for testing new chemotherapeutic agents against congenital toxoplasmosis.

  16. Influence of Trypanosoma cruzi strain on the pathogenesis of chronic myocardiopathy in mice

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    Sonia G. Andrade

    1990-03-01

    Full Text Available The murine model of chronic Chaga's myocardiopathy was developed in 201 inbred and outbred mice. The experimental groups consisted of 1st: 73 inbred AKR and A/J mice inoculated with one of the following. Trypanosoma cruzi strains: Peruvian (Type I, 12 SF (Type II or Colombian (Type III; 2nd: 128 outbred Swiss mice, chronically infected either with Type II or Type III strains isolated from human patients from different geographical areas. All T. cruzi strains were previoulsly characterized by their morphobiological behaviour in mice and by isoenzymatic patterns. For the 1st group the inoculum was 5 x 10**4 for the Peruvian strain and 1 x 10**5 for the 12 SF and Colombian strains. In the 2nd group-Swiss mice the inoculum size varied from 2 x 10**4 to 2 x 10**5. The inbred animals were killed at a 3 time-point scale (90, 180 and 240 days post-infection. The Swiss mice were killed from 180 to 660 days after infection. The evaluation of parasitemia and serology (xeodiagnosis and indirect immunofluorescent test was performed. The incidence of macroscopic alterations of the heart and cardiac index were evaluated. Histopathological lesions of the myocardium were graded. The influence of T. cruzi strain on the intensity of cardiac lesions was evaluated by the Chi-square test; the incidence of inflammatory lesions and its relationship to the parasite strain was evaluated by the Fisher test. The influence of the duration of infection was evaluated by using the Gamma Coefficient of Kruskal and Goodman and its measure of significance. Slight to severe microscopic alterations occurred in 85% of the chronically infected nice. There were a clear predominance on the incidence and intensity of inflammatory and fibrotic alterations for the mice infected with Type III strains. Statistical analysis has shown significant differences among the infected groups, in the inflammatory and fibrotic lesions. Macroscopic alterations (right cavities dilatation and apex

  17. Pseudomonas aeruginosa biofilm aggravates skin inflammatory response in BALB/c mice in a novel chronic wound model

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    Trøstrup, Hannah; Thomsen, Kim; Christophersen, Lars J

    2013-01-01

    model in C3H/HeN and BALB/c mice. The chronic wound was established by an injection of seaweed alginate-embedded P. aeruginosa PAO1 beneath a third-degree thermal lesion providing full thickness skin necrosis, as in human chronic wounds. Cultures revealed growth of PA, and both alginate with or without......Chronic wounds are presumed to persist in the inflammatory state, preventing healing. Emerging evidence indicates a clinical impact of bacterial biofilms in soft tissues, including Pseudomonas aeruginosa (PA) biofilms. To further investigate this, we developed a chronic PA biofilm wound infection...... bacteria organized in clusters, resembling biofilms, and inflammation located adjacent to the PA. The chronic wound infection showed a higher number of PAO1 in the BALB/c mice at day 4 after infection as compared to C3H/HeN mice (p

  18. Synergy of mIL-21 and mIL-15 in enhancing DNA vaccine efficacy against acute and chronic Toxoplasma gondii infection in mice.

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    Li, Zhong-Yuan; Chen, Jia; Petersen, Eskild; Zhou, Dong-Hui; Huang, Si-Yang; Song, Hui-Qun; Zhu, Xing-Quan

    2014-05-23

    The synergistic protective efficacy of murine interleukin 21 (mIL-21) and mIL-15 administrated with DNA vaccine against acute and chronic Toxoplasma gondii infection in mice was investigated using T. gondii MIC8 (TgMIC8) as a model. We cloned mIL-21 and mIL-15 from splenic tissues of Kunming mice, and constructed eukaryotic plasmid pVAX/mIL-15, pVAX/mIL-21, and pVAX/mIL-21/mIL-15, respectively. After immunizing with pVAX/TgMIC8 in the presence or absence of these cytokines, immune responses were analyzed using lymphoproliferative assay, cytokine and serum antibody measurements, flow cytometric surface markers on lymphocytes and protection against acute and chronic T. gondii infection. Mice receiving pVAX/TgMIC8 alone developed a strong humoral responses and Th1 type cellular immune responses, and showed an increase of CD4+ and CD8+ T cells compared with all the controls. Adding pVAX/mIL-21 to pVAX/TgMIC8 compared to pVAX/TgMIC8 resulted in only a slight increase in humoral and cellular immune responses, and this immune response was lower than that induced by the pVAX/mIL-15 combined with pVAX/TgMIC8. Co-administration of pVAX/mIL-21/mIL-15 combined with pVAX/TgMIC8 elicited the strongest humoral and cellular immune responses among all the groups, leading to significantly increased survival time against acute infection and the significant reduction of tissue cysts, compared to all the controls. Synergy of mIL-21 and mIL-15 can facilitate specific humoral as well as cellular immune responses elicited by DNA vaccine against acute and chronic T. gondii infection in mice. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Cytokine and surface receptor diversity of NK cells in resistant C3H/HeN and susceptible BALB/c mice with chronic Pseudomonas aeruginosa lung infection

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    Calum, Henrik; Moser, Claus; Jensen, Peter Østrup

    2003-01-01

    The purpose of the present study was to investigate whether NK cells from resistant C3H/HeN mice and susceptible BALB/c mice showed different release of cytokines and expression of surface molecules during chronic P. aeruginosa lung infection using alginate-embedded P. aeruginosa mimicking...... the infection in cystic fibrosis. Lung cell suspensions were depleted of lymphocytes by magnetic cell sorting. The concentrations of IFN-gamma, IL-1beta and GM-CSF were estimated by ELISA at day 1 and 2 after infection. Non-infected mice were used as controls. Flow cytometry was used to estimate the surface...... expression of the LFA-1 and Fc receptors on NK cells. At day 2, IFN-gamma levels increased in C3H/HeN mice but decreased in BALB/c mice. The GM-CSF levels increased only in the C3H/HeN mice at day 1 and 2. Surface expression of LFA-1 on the NK cells was higher in C3H/HeN mice at day 1 and 2. In contrast...

  20. Interleukin-13 is involved in the formation of liver fibrosis in Clonorchis sinensis-infected mice.

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    Xu, Yanquan; Liang, Pei; Bian, Meng; Chen, Wenjun; Wang, Xiaoyun; Lin, Jinsi; Shang, Mei; Qu, Hongling; Wu, Zhongdao; Huang, Yan; Yu, Xinbing

    2016-07-01

    Clonorchiasis is a chronic infection disease often accompanied by formation of liver fibrosis. Previous study has identified that Clonorchis sinensis (C. sinensis, Cs) infection and CsRNASET2 (a member of CsESPs) immunization can drive Th2 immune response. IL-13, a multifunctional Th2 cytokine, has been widely confirmed to be profibrotic mediator. We want to determine whether IL-13 is involved in the generation of liver fibrosis during C. sinensis infection. A part of mice were infected with C. sinensis or immunized with CsRNASET2, respectively. Another part of mice were intravenously injected with rIL-13. Liver tissues of C. sinensis-infected mice were stained with hematoxylin-eosin and Masson's trichrome, respectively. The transcriptional levels of collagen-I, collagen-III, α-SMA, and TIMP-1 in the livers of infected mice and rIL-13-treated mice were measured by quantitative RT-PCR. Besides, splenocytes of C. sinensis-infected and CsRNASET2-immunized mice were isolated, respectively. The levels of IL-13 in splenocytes were detected by ELISA. Our results displayed that the livers of C. sinensis-infected mice had serious chronic inflammation and collagen deposition. The transcriptional levels of collagen-I, collagen-III, α-SMA, and TIMP-1 in the livers of C. sinensis-infected mice were obviously increased. Splenocytes from both C. sinensis-infected and CsRNASET2-immunized mice expressed high levels of IL-13. Moreover, rIL-13 treatment markedly promoted the transcriptional levels of collagen-I, collagen-III, α-SMA, and TIMP-1. These data implied that hepatic fibrosis was formed in the livers of C. sinensis-infected mice, and IL-13 induced by C. sinensis infection and CsRNASET2 immunization might favor this progression.

  1. T-cell-dependent control of acute Giardia lamblia infections in mice.

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    Singer, S M; Nash, T E

    2000-01-01

    We have studied immune mechanisms responsible for control of acute Giardia lamblia and Giardia muris infections in adult mice. Association of chronic G. lamblia infection with hypogammaglobulinemia and experimental infections of mice with G. muris have led to the hypothesis that antibodies are required to control these infections. We directly tested this hypothesis by infecting B-cell-deficient mice with either G. lamblia or G. muris. Both wild-type mice and B-cell-deficient mice eliminated the vast majority of parasites between 1 and 2 weeks postinfection with G. lamblia. G. muris was also eliminated in both wild-type and B-cell-deficient mice. In contrast, T-cell-deficient and scid mice failed to control G. lamblia infections, as has been shown previously for G. muris. Treatment of wild-type or B-cell-deficient mice with antibodies to CD4 also prevented elimination of G. lamblia, confirming a role for T cells in controlling infections. By infecting mice deficient in either alphabeta- or gammadelta-T-cell receptor (TCR)-expressing T cells, we show that the alphabeta-TCR-expressing T cells are required to control parasites but that the gammadelta-TCR-expressing T cells are not. Finally, infections in mice deficient in production of gamma interferon or interleukin 4 (IL-4) and mice deficient in responding to IL-4 and IL-13 revealed that neither the Th1 nor the Th2 subset is absolutely required for protection from G. lamblia. We conclude that a T-cell-dependent mechanism is essential for controlling acute Giardia infections and that this mechanism is independent of antibody and B cells.

  2. Autoreactive T Cells and Chronic Fungal Infection Drive Esophageal Carcinogenesis

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    Zhu, Feng; Willette-Brown, Jami; Song, Na-Young; Lomada, Dakshayani; Song, Yongmei; Xue, Liyan; Gray, Zane; Zhao, Zitong; Davis, Sean R.; Sun, Zhonghe; Zhang, Peilin; Wu, Xiaolin; Zhan, Qimin; Richie, Ellen R.; Hu, Yinling

    2018-01-01

    SUMMARY Humans with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a T cell–driven autoimmune disease caused by impaired central tolerance, are susceptible to developing chronic fungal infection and esophageal squamous cell carcinoma (ESCC). However, the relationship between autoreactive T cells and chronic fungal infection in ESCC development remains unclear. We find that kinase-dead Ikkα knockin mice develop phenotypes reminiscent of APECED, including impaired central tolerance, autoreactive T cells, chronic fungal infection, and ESCCs expressing specific human ESCC markers. Using this model, we investigated the potential link between ESCC and fungal infection. Autoreactive CD4 T cells permit fungal infection and incite tissue injury and inflammation. Antifungal treatment or depletion of autoreactive CD4 T cells rescues, whereas oral fungal administration promotes, ESCC development. Inhibition of inflammation or EGFR activity decreases fungal burden. Importantly, fungal infection is highly associated with ESCCs in non-autoimmune human patients. Therefore, autoreactive T cells and chronic fungal infection, fostered by inflammation and epithelial injury, promote ESCC development. PMID:28407484

  3. Activation of pulmonary and lymph node dendritic cells during chronic Pseudomonas aeruginosa lung infection in mice

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    Damlund, Dina S. M.; Christophersen, Lars; Jensen, Peter Østrup

    2016-01-01

    , the infection is not eradicated and the inflammatory response leads to gradual degradation of the lung tissue. In CF patients, a Th2-dominated adaptive immune response with a pronounced antibody response is correlated with poorer outcome. Dendritic cells (DCs) are crucial in bridging the innate immune system...... with the adaptive immune response. Once activated, the DCs deliver a set of signals to uncommitted T cells that induce development, such as expansion of regulatory T cells and polarization of Th1, Th2 or Th17 subsets. In this study, we characterized DCs in lungs and regional lymph nodes in BALB/c mice infected...... using intratracheal installation of P. aeruginosa embedded in seaweed alginate in the lungs. A significantly elevated concentration of DCs was detected earlier in the lungs than in the regional lymph nodes. To evaluate whether the chronic P. aeruginosa lung infection leads to activation of DCs...

  4. Low dose chronic Schistosoma mansoni infection increases susceptibility to Mycobacterium bovis BCG infection in mice

    DEFF Research Database (Denmark)

    Elias, D; Akuffo, H; Thors, C

    2005-01-01

    The incidence of mycobacterial diseases is high and the efficacy of Bacillus Calmette Guerin (BCG) is low in most areas of the world where chronic worm infections are common. However, if and how concurrent worm infections could affect immunity to mycobacterial infections has not been elucidated. ...

  5. Prion Infectivity in Fat of Deer with Chronic Wasting Disease▿

    OpenAIRE

    Race, Brent; Meade-White, Kimberly; Race, Richard; Chesebro, Bruce

    2009-01-01

    Chronic wasting disease (CWD) is a neurodegenerative prion disease of cervids. Some animal prion diseases, such as bovine spongiform encephalopathy, can infect humans; however, human susceptibility to CWD is unknown. In ruminants, prion infectivity is found in central nervous system and lymphoid tissues, with smaller amounts in intestine and muscle. In mice, prion infectivity was recently detected in fat. Since ruminant fat is consumed by humans and fed to animals, we determined infectivity t...

  6. Parasitic loads in tissues of mice infected with Trypanosoma cruzi and treated with AmBisome.

    Directory of Open Access Journals (Sweden)

    Sabrina Cencig

    2011-06-01

    Full Text Available BACKGROUND: Chagas disease is one of the most important public health problems and a leading cause of cardiac failure in Latin America. The currently available drugs to treat T. cruzi infection (benznidazole and nifurtimox are effective in humans when administered during months. AmBisome (liposomal amphotericin B, already shown efficient after administration for some days in human and experimental infection with Leishmania, has been scarcely studied in T. cruzi infection. AIMS: This work investigates the effect of AmBisome treatment, administered in 6 intraperitoneal injections at various times during acute and/or chronic phases of mouse T. cruzi infection, comparing survival rates and parasitic loads in several tissues. METHODOLOGY: Quantitative PCR was used to determine parasitic DNA amounts in tissues. Immunosuppressive treatment with cyclophosphamide was used to investigate residual infection in tissues. FINDINGS: Administration of AmBisome during the acute phase of infection prevented mice from fatal issue. Parasitaemias (microscopic examination were reduced in acute phase and undetectable in chronic infection. Quantitative PCR analyses showed significant parasite load reductions in heart, liver, spleen, skeletal muscle and adipose tissues in acute as well as in chronic infection. An earlier administration of AmBisome (one day after parasite inoculation had a better effect in reducing parasite loads in spleen and liver, whereas repetition of treatment in chronic phase enhanced the parasite load reduction in heart and liver. However, whatever the treatment schedule, cyclophosphamide injections boosted infection to parasite amounts comparable to those observed in acutely infected and untreated mice. CONCLUSIONS: Though AmBisome treatment fails to completely cure mice from T. cruzi infection, it impedes mortality and reduces significantly the parasitic loads in most tissues. Such a beneficial effect, obtained by administrating it over a short

  7. Polyclonal immunoglobulins from a chronic hepatitis C virus patient protect human liver-chimeric mice from infection with a homologous hepatitis C virus strain

    DEFF Research Database (Denmark)

    Vanwolleghem, Thomas; Bukh, Jens; Meuleman, Philip

    2008-01-01

    The role of the humoral immune response in the natural course of hepatitis C virus (HCV) infection is widely debated. Most chronically infected patients have immunoglobulin G (IgG) antibodies capable of neutralizing HCV pseudoparticles (HCVpp) in vitro. It is, however, not clear whether these Ig...... were loaded with chronic phase polyclonal IgG and challenged 3 days later with a 100% infectious dose of the acute phase H77C virus, both originating from patient H. Passive immunization induced sterilizing immunity in five of eight challenged animals. In the three nonprotected animals, the HCV...... infection was attenuated, as evidenced by altered viral kinetics in comparison with five control IgG-treated animals. Plasma samples obtained from the mice at viral challenge neutralized H77C-HCVpp at dilutions as high as 1/400. Infection was completely prevented when, before administration to naïve...

  8. Chronic oral infection with major periodontal bacteria Tannerella forsythia modulates systemic atherosclerosis risk factors and inflammatory markers.

    Science.gov (United States)

    Chukkapalli, Sasanka S; Rivera-Kweh, Mercedes F; Velsko, Irina M; Chen, Hao; Zheng, Donghang; Bhattacharyya, Indraneel; Gangula, Pandu R; Lucas, Alexandra R; Kesavalu, Lakshmyya

    2015-04-01

    Tannerella forsythia is a Gram-negative anaerobic organism that inhabits the subgingival cavity and initiates connective tissue destruction and alveolar bone resorption in periodontal disease (PD). PD is a chronic immunoinflammatory disease and has been linked to several systemic diseases including atherosclerosis. This study evaluated the effects of a chronic oral infection with T. forsythia ATCC 43037 on the induction of PD, inflammatory markers and atherosclerosis risk factors in hyperlipidemic ApoE(null) mice. Mice were orally infected for 12 and 24 weeks prior to euthanasia. Bacterial colonization of the oral cavity and bacteremia was confirmed via isolation of genomic DNA from oral plaque and tissues. Oral infection elicited significantly elevated levels of serum IgG and IgM antibodies and alveolar bone resorption compared to control mice. Tannerella forsythia-infected mice had increased serum amyloid A, and significantly reduced serum nitric oxide when compared to controls. Tannerella forsythia chronic infection also significantly increased serum lipoproteins suggesting altered cholesterol metabolism and potential for aortic inflammation. Despite enhanced acute phase reactants and altered lipid profiles, T. forsythia infection was associated with decreased aortic plaque. This study investigates the potential of a known periodontal bacterial pathogen found in atherosclerotic plaque in humans to accelerate atherosclerosis in hyperlipdemic mice. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Induction of premalignant host responses by cathepsin x/z-deficiency in Helicobacter pylori-infected mice.

    Directory of Open Access Journals (Sweden)

    Sabine Krueger

    Full Text Available Helicobacter pylori are responsible for the induction of chronic gastric inflammation progressing to atrophy, metaplasia, and gastric cancer. The overexpression of Cathepsin X/Z (Ctsz in H. pylori-infected mucosa and gastric cancer is mediated predominantly by an augmented migration of ctsz(-/-positive macrophages and the up-regulation of Ctsz in tumor epithelium. To explore the Ctsz-function in the context of chronic inflammation and the development of preneoplastic lesions, we used Ctsz-deficient mice in a H. pylori gastritis model. Ctsz (-/- and wild-type (wt mice were infected with H. pylori strain SS1. The mice were sacrificed at 24, 36, and 50 weeks post infection (wpi. The stomach was removed, and gastric strips were snap-frozen or embedded and stained with H&E. Tissue sections were scored for epithelial lesions and inflammation. Ki-67 and F4/80 immunostaining were used to measure epithelial cell proliferation and macrophage infiltration, respectively. The upregulation of compensating cathepsins and cytokines were confirmed by Western blotting and quantitative RT-PCR. SS1-infected wt and ctsz (-/- mice showed strong inflammation, foveolar hyperplasia, atrophy, and cystically-dilated glands. However, at 50 wpi, ctsz (-/- mice developed significantly more severe spasmolytic polypeptide-expressing metaplasia (SPEM, showed enhanced epithelial proliferation, and higher levels of infiltrating macrophages. Induction of cytokines was higher and significantly prolonged in ctsz (-/- mice compared to wt. Ctsz deficiency supports H. pylori-dependent development of chronic gastritis up to metaplasia, indicating a protective, but not proteolytic, function of Ctsz in inflammatory gastric disease.

  10. Chronic Giardia muris infection in anti-IgM-treated mice. I. Analysis of immunoglobulin and parasite-specific antibody in normal and immunoglobulin-deficient animals.

    Science.gov (United States)

    Snider, D P; Gordon, J; McDermott, M R; Underdown, B J

    1985-06-01

    To investigate the role of B cells and antibody in the immune response of mice to the murine intestinal parasite Giardia muris, we used mice treated from birth with rabbit anti-IgM antisera (aIgM). Such mice developed in serum and in gut secretions extreme Ig deficiency (IgM, IgA, and IgG) relative to control animals. The aIgM-treated mice showed no anti-G. muris antibody in serum or in gut wash material. Infections of G. muris in these mice were chronic, with a high load of parasite present in the small bowel, as reflected by prolonged cyst excretion (greater than 11 wk) and high trophozoite counts. In contrast, normal, untreated mice or NRS-treated animals developed anti-parasite IgA and IgG antibody in serum, demonstrated IgA antibody against the parasite in gut washings, and expelled the parasite within 9 wk. These effects of aIgM treatment on the murine response to primary infection with G. muris were demonstrated in two strains of mice: BALB/c and (C57BL/6 X C3H/He) F1. It was also observed that the response to G. muris infection in untreated animals was characterized by higher than normal total secretion of IgA into the gut and a concomitant increase in the serum polymeric IgA level. Mice treated with aIgM had a marked decrease of both monomeric and polymeric IgA in serum, and little detectable IgA in the intestinal lumen. These experiments provide the first demonstration that anti-IgM treatment suppresses a specific intestinal antibody response to antigen, and provide evidence that B cells and antibody play a role in the development of an effective response to a primary infection with G. muris in mice.

  11. Effect of treatment with cyclophosphamide in low doses upon the onset of delayed type hypersensitivity in mice chronically infected with Trypanosoma cruzi: involvement of heart interstitial dendritic cells

    Directory of Open Access Journals (Sweden)

    Torriceli Souza The

    2013-09-01

    Full Text Available Acute infection with Trypanosoma cruzi results in intense myocarditis, which progresses to a chronic, asymptomatic indeterminate form. The evolution toward this chronic cardiac form occurs in approximately 30% of all cases of T. cruzi infection. Suppression of delayed type hypersensitivity (DTH has been proposed as a potential explanation of the indeterminate form. We investigated the effect of cyclophosphamide (CYCL treatment on the regulatory mechanism of DTH and the participation of heart interstitial dendritic cells (IDCs in this process using BALB/c mice chronically infected with T. cruzi. One group was treated with CYCL (20 mg/kg body weight for one month. A DTH skin test was performed by intradermal injection of T. cruzi antigen (3 mg/mL in the hind-footpad and measured the skin thickness after 24 h, 48 h and 72 h. The skin test revealed increased thickness in antigen-injected footpads, which was more evident in the mice treated with CYCL than in those mice that did not receive treatment. The thickened regions were characterised by perivascular infiltrates and areas of necrosis. Intense lesions of the myocardium were present in three/16 cases and included large areas of necrosis. Morphometric evaluation of lymphocytes showed a predominance of TCD8 cells. Heart IDCs were immunolabelled with specific antibodies (CD11b and CD11c and T. cruzi antigens were detected using a specific anti-T. cruzi antibody. Identification of T. cruzi antigens, sequestered in these cells using specific anti-T. cruzi antibodies was done, showing a significant increase in the number of these cells in treated mice. These results indicate that IDCs participate in the regulatory mechanisms of DTH response to T. cruzi infection.

  12. Dental Infection of Porphyromonas gingivalis Induces Preterm Birth in Mice.

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    Min Ao

    Full Text Available Epidemiological studies have revealed a link between dental infection and preterm birth or low birth weight (PTB/LBW, however, the underlying mechanisms remain unclear. Progress in understanding the associated mechanisms has been limited in part by lack of an animal model for chronic infection-induced PTB/LBW, mimicking pregnancy under conditions of periodontitis. We aimed to establish a mouse model of chronic periodontitis in order to investigate the link between periodontitis and PTB/LBW.To establish chronic inflammation beginning with dental infection, we surgically opened mouse (female, 8 weeks old 1st molar pulp chambers and directly infected with w83 strain Porphyromonas gingivalis (P.g., a keystone periodontal pathogen. Mating was initiated at 6 wks post-infection, by which time dental granuloma tissue had developed and live P.g. was cultured from extracted tooth root, which serves as a persistent source of P.g. The gestational day (gd and birth weight were recorded during for P.g.-infected and control mice, and serum and placental tissues were collected at gd 15 to evaluate the systemic and local conditions during pregnancy.Dental infection with P.g. significantly increased circulating TNF-α (2.5-fold, IL-17 (2-fold, IL-6 (2-fold and IL-1β (2-fold. The P.g.-infected group delivered at gd 18.25 vs. gd 20.45 in the non-infected control (NC group (p < 0.01, and pups exhibited LBW compared to controls (p < 0.01. P.g. was localized to placental tissues by immunohistochemistry and PCR, and defects in placental tissues of P.g. infected mice included premature rupture of membrane, placental detachment, degenerative changes in trophoblasts and endothelial cells, including necrotic areas. P.g. infection caused significantly increased numbers of polymorphonuclear leukocytes (PMNLs and macrophages in placental tissues, associated with increased local expression of pro-inflammatory mediators including TNF-α and COX-2. Further placental tissue

  13. Chronic schistosomiasis during pregnancy epigenetically reprograms T-cell differentiation in offspring of infected mothers.

    Science.gov (United States)

    Klar, Kathrin; Perchermeier, Sophie; Bhattacharjee, Sonakshi; Harb, Hani; Adler, Thure; Istvanffy, Rouzanna; Loffredo-Verde, Eva; Oostendorp, Robert A; Renz, Harald; Prazeres da Costa, Clarissa

    2017-05-01

    Schistosomiasis is a nontransplacental helminth infection. Chronic infection during pregnancy suppresses allergic airway responses in offspring. We addressed the question whether in utero exposure to chronic schistosome infection (Reg phase) in mice affects B-cell and T-cell development. Therefore, we focused our analyses on T-cell differentiation capacity induced by epigenetic changes in promoter regions of signature cytokines in offspring. Here, we show that naïve T cells from offspring of schistosome infected female mice had a strong capacity to differentiate into T H 1 cells, whereas T H 2 differentiation was impaired. In accordance, reduced levels of histone acetylation of the IL-4 promoter regions were observed in naïve T cells. To conclude, our mouse model revealed distinct epigenetic changes within the naïve T-cell compartment affecting T H 2 and T H 1 cell differentiation in offspring of mothers with chronic helminth infection. These findings could eventually help understand how helminths alter T-cell driven immune responses induced by allergens, bacterial or viral infections, as well as vaccines. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Cytokine and surface receptor diversity of NK cells in resistant C3H/HeN and susceptible BALB/c mice with chronic Pseudomonas aeruginosa lung infection

    DEFF Research Database (Denmark)

    Calum, Henrik; Moser, Claus; Jensen, Peter Østrup

    2003-01-01

    The purpose of the present study was to investigate whether NK cells from resistant C3H/HeN mice and susceptible BALB/c mice showed different release of cytokines and expression of surface molecules during chronic P. aeruginosa lung infection using alginate-embedded P. aeruginosa mimicking...... expression of the LFA-1 and Fc receptors on NK cells. At day 2, IFN-gamma levels increased in C3H/HeN mice but decreased in BALB/c mice. The GM-CSF levels increased only in the C3H/HeN mice at day 1 and 2. Surface expression of LFA-1 on the NK cells was higher in C3H/HeN mice at day 1 and 2. In contrast...

  15. Effect of chronic irradiation combined with other damaging factors on some morphological systems of mice

    International Nuclear Information System (INIS)

    Ponomareva, T.V.; Merkushev, G.N.; Pil'shchuk, E.M.; Bikkulov, R.I.

    1978-01-01

    A model experiment on mice is carried out to study morphofunctional changes that occur in mammals chronically exposed to radiation in doses close to those in occupational exposures of a man. Mice have been exposed to gamma-radiation at dose rates of 6, 16, 40, 120, and 300 mr/day from the time of birth onward throughout lifetime. It is concluded that, where a chronic purulent infection is present, chronic irradiation at the above dose rates, with the exception of 6 mr/day, accelerates the onset of irreversible pathologic changes, in particular of amyloidosis, in immunocompetent organs

  16. Major role for carbohydrate epitopes preferentially recognized by chronically infected mice in the determination of Schistosoma mansoni schistosomulum surface antigenicity

    International Nuclear Information System (INIS)

    Omer-ali, P.; Magee, A.I.; Kelly, C.; Simpson, A.J.G.

    1986-01-01

    A radioimmunoassay that makes use of whole Schistosomula and 125 I-labeled protein A has been used to characterize and to quantify the binding of antisera to the surface of 3 hr mechanically transformed schistosomula of Schistosoma mansoni. This technique facilitates the determination of epitopes on the schistosomula in addition to those detected by surface labeling and immunoprecipitation. By using this technique, it has been demonstrated that there is a much greater binding to the parasite surface of antibodies from chronically infected mice (CMS) than of antibodies from mice infected with highly irradiated cercariae (VMS), and CMS recognizes epitopes that VMS does not. Treatment of the surface of the schistosomula with trifluoromethanesulphonic acid and sodium metaperiodate has suggested that the discrepancy of the binding between the two sera is due to the recognition of a large number of additional epitopes by CMS, which are carbohydrate in nature. Some of the carbohydrate epitopes are expressed on the previously described surface glycoprotein antigens of M/sub r/ 200,000, 38,000, and 17,000

  17. Early-life viral infection and allergen exposure interact to induce an asthmatic phenotype in mice

    Directory of Open Access Journals (Sweden)

    Asquith Kelly L

    2010-02-01

    Full Text Available Abstract Background Early-life respiratory viral infections, notably with respiratory syncytial virus (RSV, increase the risk of subsequent development of childhood asthma. The purpose of this study was to assess whether early-life infection with a species-specific model of RSV and subsequent allergen exposure predisposed to the development of features of asthma. Methods We employed a unique combination of animal models in which BALB/c mice were neonatally infected with pneumonia virus of mice (PVM, which replicates severe RSV disease in human infants and following recovery, were intranasally sensitised with ovalbumin. Animals received low-level challenge with aerosolised antigen for 4 weeks to elicit changes of chronic asthma, followed by a single moderate-level challenge to induce an exacerbation of inflammation. We then assessed airway inflammation, epithelial changes characteristic of remodelling, airway hyperresponsiveness (AHR and host immunological responses. Results Allergic airway inflammation, including recruitment of eosinophils, was prominent only in animals that had recovered from neonatal infection with PVM and then been sensitised and chronically challenged with antigen. Furthermore, only these mice exhibited an augmented Th2-biased immune response, including elevated serum levels of anti-ovalbumin IgE and IgG1 as well as increased relative expression of Th2-associated cytokines IL-4, IL-5 and IL-13. By comparison, development of AHR and mucous cell change were associated with recovery from PVM infection, regardless of subsequent allergen challenge. Increased expression of IL-25, which could contribute to induction of a Th2 response, was demonstrable in the lung following PVM infection. Signalling via the IL-4 receptor α chain was crucial to the development of allergic inflammation, mucous cell change and AHR, because all of these were absent in receptor-deficient mice. In contrast, changes of remodelling were evident in mice

  18. Immune response in the adipose tissue of lean mice infected with the protozoan parasite Neospora caninum

    Science.gov (United States)

    Teixeira, Luzia; Moreira, João; Melo, Joana; Bezerra, Filipa; Marques, Raquel M; Ferreirinha, Pedro; Correia, Alexandra; Monteiro, Mariana P; Ferreira, Paula G; Vilanova, Manuel

    2015-01-01

    The adipose tissue can make important contributions to immune function. Nevertheless, only a limited number of reports have investigated in lean hosts the immune response elicited in this tissue upon infection. Previous studies suggested that the intracellular protozoan Neospora caninum might affect adipose tissue physiology. Therefore, we investigated in mice challenged with this protozoan if immune cell populations within adipose tissue of different anatomical locations could be differently affected. Early in infection, parasites were detected in the adipose tissue and by 7 days of infection increased numbers of macrophages, regulatory T (Treg) cells and T-bet+ cells were observed in gonadal, mesenteric, omental and subcutaneous adipose tissue. Increased expression of interferon-γ was also detected in gonadal adipose tissue of infected mice. Two months after infection, parasite DNA was no longer detected in these tissues, but T helper type 1 (Th1) cell numbers remained above control levels in the infected mice. Moreover, the Th1/Treg cell ratio was higher than that of controls in the mesenteric and subcutaneous adipose tissue. Interestingly, chronically infected mice presented a marked increase of serum leptin, a molecule that plays a role in energy balance regulation as well as in promoting Th1-type immune responses. Altogether, we show that an apicomplexa parasitic infection influences immune cellular composition of adipose tissue throughout the body as well as adipokine production, still noticed at a chronic phase of infection when parasites were already cleared from that particular tissue. This strengthens the emerging view that infections can have long-term consequences for the physiology of adipose tissue. PMID:25581844

  19. Mycobacterium tuberculosis from chronic murine infections that grows in liquid but not on solid medium

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    Mitchison Denis A

    2004-11-01

    Full Text Available Abstract Background Old, stationary cultures of Mycobacterium tuberculosis contain a majority of bacteria that can grow in broth cultures but cannot grow on solid medium plates. These may be in a non-replicating, dormant growth phase. We hypothesised that a similar population might be present in chronic, murine tuberculosis. Methods Estimates of the numbers of viable M. tuberculosis, strain H37Rv, in the spleens and lungs of mice in a 7-day acute infection and in a 10-month chronic infection were made by conventional plate counts and, as broth counts, by noting presence or absence of growth in serial replicate dilutions in liquid medium. Results Plate and broth counts in 6 mice gave similar mean values in the acute infection, 7 days after infection. However, the broth counts were much higher in 36 mice with a chronic infection at 10 months. Broth counts averaged 5.290 log10 cfu /organ from spleens and 5.523 log10 cfu/organ from lungs, while plate counts were 3.858 log10 cfu/organ from spleens and 3.662 log10 cfu/organ from lungs, indicating that the total bacterial population contained only 3.7% bacilli in spleens and 1.4% bacilli in lungs, capable of growth on plates. Conclusion The proportion growing on plates might be a measure of the "dormancy" of the bacilli equally applicable to cultural and animal models.

  20. Toxoplasma gondii oral infection induces intestinal inflammation and retinochoroiditis in mice genetically selected for immune oral tolerance resistance.

    Directory of Open Access Journals (Sweden)

    Raul Ramos Furtado Dias

    Full Text Available Toxoplasmosis is a worldwide disease with most of the infections originating through the oral route and generates various pathological manifestations, ranging from meningoencephalitis to retinochoroiditis and inflammatory bowel disease. Animal models for these pathologies are scarce and have limitations. We evaluated the outcome of Toxoplasma gondii oral infection with 50 or 100 cysts of the ME-49 strain in two lines of mice with extreme phenotypes of susceptibility (TS or resistance (TR to immune oral tolerance. Therefore, the aim of this study was to evaluate the behaviour of TS and TR mice, orally infected by T. gondii, and determine its value as a model for inflammatory diseases study. Mortality during the acute stage of the infection for TR was 50% for both dosages, while 10 and 40% of the TS died after infection with these respective dosages. In the chronic stage, the remaining TS succumbed while TR survived for 90 days. The TS displayed higher parasite load with lower intestinal inflammation and cellular proliferation, notwithstanding myocarditis, pneumonitis and meningoencephalitis. TR presented massive necrosis of villi and crypt, comparable to inflammatory bowel disease, with infiltration of lymphoid cells in the lamina propria of the intestines. Also, TR mice infected with 100 cysts presented intense cellular infiltrate within the photoreceptor layer of the eyes, changes in disposition and morphology of the retina cell layers and retinochoroiditis. During the infection, high levels of IL-6 were detected in the serum of TS mice and TR mice presented high amounts of IFN-γ and TNF-α. Both mice lineages developed different disease outcomes, but it is emphasized that TR and TS mice presented acute and chronic stages of the infection, demonstrating that the two lineages offer an attractive model for studying toxoplasmosis.

  1. Toxoplasma gondii Oral Infection Induces Intestinal Inflammation and Retinochoroiditis in Mice Genetically Selected for Immune Oral Tolerance Resistance

    Science.gov (United States)

    Dias, Raul Ramos Furtado; de Carvalho, Eulógio Carlos Queiroz; Leite, Carla Cristina da Silva; Tedesco, Roberto Carlos; Calabrese, Katia da Silva; Silva, Antonio Carlos; DaMatta, Renato Augusto; de Fatima Sarro-Silva, Maria

    2014-01-01

    Toxoplasmosis is a worldwide disease with most of the infections originating through the oral route and generates various pathological manifestations, ranging from meningoencephalitis to retinochoroiditis and inflammatory bowel disease. Animal models for these pathologies are scarce and have limitations. We evaluated the outcome of Toxoplasma gondii oral infection with 50 or 100 cysts of the ME-49 strain in two lines of mice with extreme phenotypes of susceptibility (TS) or resistance (TR) to immune oral tolerance. Therefore, the aim of this study was to evaluate the behaviour of TS and TR mice, orally infected by T. gondii, and determine its value as a model for inflammatory diseases study. Mortality during the acute stage of the infection for TR was 50% for both dosages, while 10 and 40% of the TS died after infection with these respective dosages. In the chronic stage, the remaining TS succumbed while TR survived for 90 days. The TS displayed higher parasite load with lower intestinal inflammation and cellular proliferation, notwithstanding myocarditis, pneumonitis and meningoencephalitis. TR presented massive necrosis of villi and crypt, comparable to inflammatory bowel disease, with infiltration of lymphoid cells in the lamina propria of the intestines. Also, TR mice infected with 100 cysts presented intense cellular infiltrate within the photoreceptor layer of the eyes, changes in disposition and morphology of the retina cell layers and retinochoroiditis. During the infection, high levels of IL-6 were detected in the serum of TS mice and TR mice presented high amounts of IFN-γ and TNF-α. Both mice lineages developed different disease outcomes, but it is emphasized that TR and TS mice presented acute and chronic stages of the infection, demonstrating that the two lineages offer an attractive model for studying toxoplasmosis. PMID:25437299

  2. Respiratory syncytial virus infection facilitates acute colonization of Pseudomonas aeruginosa in mice

    DEFF Research Database (Denmark)

    de Vrankrijker, Angélica M M; Wolfs, Tom F W; Ciofu, Oana

    2009-01-01

    virus infections in facilitating colonization and infection with P. aeruginosa. A study was undertaken to determine whether respiratory syncytial virus (RSV) infection could facilitate the initiation of an acute infection with P. aeruginosa in vivo. Balb/c mice were infected intranasally with P......Pseudomonas aeruginosa causes opportunistic infections in immunocompromised individuals and patients ventilated mechanically and is the major pathogen in patients with cystic fibrosis, in which it causes chronic infections. Epidemiological, in vitro and animal data suggest a role for respiratory....... These results suggest that RSV can facilitate the initiation of acute P. aeruginosa infection without the RSV infection being clinically apparent. This could have implications for treatment strategies to prevent opportunistic P. aeruginosa lung infection....

  3. Toxoplasma gondii Infection in Mice Impairs Long-Term Fear Memory Consolidation through Dysfunction of the Cortex and Amygdala.

    Science.gov (United States)

    Ihara, Fumiaki; Nishimura, Maki; Muroi, Yoshikage; Mahmoud, Motamed Elsayed; Yokoyama, Naoaki; Nagamune, Kisaburo; Nishikawa, Yoshifumi

    2016-10-01

    Chronic infection with Toxoplasma gondii becomes established in tissues of the central nervous system, where parasites may directly or indirectly modulate neuronal function. Epidemiological studies have revealed that chronic infection in humans is a risk factor for developing mental diseases. However, the mechanisms underlying parasite-induced neuronal dysfunction in the brain remain unclear. Here, we examined memory associated with conditioned fear in mice and found that T. gondii infection impairs consolidation of conditioned fear memory. To examine the brain pathology induced by T. gondii infection, we analyzed the parasite load and histopathological changes. T. gondii infects all brain areas, yet the cortex exhibits more severe tissue damage than other regions. We measured neurotransmitter levels in the cortex and amygdala because these regions are involved in fear memory expression. The levels of dopamine metabolites but not those of dopamine were increased in the cortex of infected mice compared with those in the cortex of uninfected mice. In contrast, serotonin levels were decreased in the amygdala and norepinephrine levels were decreased in the cortex and amygdala of infected mice. The levels of cortical dopamine metabolites were associated with the time spent freezing in the fear-conditioning test. These results suggest that T. gondii infection affects fear memory through dysfunction of the cortex and amygdala. Our findings provide insight into the mechanisms underlying the neurological changes seen during T. gondii infection. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  4. Infection with Porphyromonas gingivalis exacerbates endothelial injury in obese mice.

    Directory of Open Access Journals (Sweden)

    Min Ao

    Full Text Available BACKGROUND: A number of studies have revealed a link between chronic periodontitis and cardiovascular disease in obese patients. However, there is little information about the influence of periodontitis-associated bacteria, Porphyromonas gingivalis (Pg, on pathogenesis of atherosclerosis in obesity. METHODS: In vivo experiment: C57BL/6J mice were fed with a high-fat diet (HFD or normal chow diet (CD, as a control. Pg was infected from the pulp chamber. At 6 weeks post-infection, histological and immunohistochemical analysis of aortal tissues was performed. In vitro experiment: hTERT-immortalized human umbilical vein endothelial cells (HuhT1 were used to assess the effect of Pg/Pg-LPS on free fatty acid (FFA induced endothelial cells apoptosis and regulation of cytokine gene expression. RESULTS: Weaker staining of CD31 and increased numbers of TUNEL positive cells in aortal tissue of HFD mice indicated endothelial injury. Pg infection exacerbated the endothelial injury. Immunohistochemically, Pg was detected deep in the smooth muscle of the aorta, and the number of Pg cells in the aortal wall was higher in HFD mice than in CD mice. Moreover, in vitro, FFA treatment induced apoptosis in HuhT1 cells and exposure to Pg-LPS increased this effect. In addition, Pg and Pg-LPS both attenuated cytokine production in HuhT1 cells stimulated by palmitate. CONCLUSIONS: Dental infection of Pg may contribute to pathogenesis of atherosclerosis by accelerating FFA-induced endothelial injury.

  5. Bidirectional brain-gut interactions and chronic pathological changes after traumatic brain injury in mice.

    Science.gov (United States)

    Ma, Elise L; Smith, Allen D; Desai, Neemesh; Cheung, Lumei; Hanscom, Marie; Stoica, Bogdan A; Loane, David J; Shea-Donohue, Terez; Faden, Alan I

    2017-11-01

    Traumatic brain injury (TBI) has complex effects on the gastrointestinal tract that are associated with TBI-related morbidity and mortality. We examined changes in mucosal barrier properties and enteric glial cell response in the gut after experimental TBI in mice, as well as effects of the enteric pathogen Citrobacter rodentium (Cr) on both gut and brain after injury. Moderate-level TBI was induced in C57BL/6mice by controlled cortical impact (CCI). Mucosal barrier function was assessed by transepithelial resistance, fluorescent-labelled dextran flux, and quantification of tight junction proteins. Enteric glial cell number and activation were measured by Sox10 expression and GFAP reactivity, respectively. Separate groups of mice were challenged with Cr infection during the chronic phase of TBI, and host immune response, barrier integrity, enteric glial cell reactivity, and progression of brain injury and inflammation were assessed. Chronic CCI induced changes in colon morphology, including increased mucosal depth and smooth muscle thickening. At day 28 post-CCI, increased paracellular permeability and decreased claudin-1 mRNA and protein expression were observed in the absence of inflammation in the colon. Colonic glial cell GFAP and Sox10 expression were significantly increased 28days after brain injury. Clearance of Cr and upregulation of Th1/Th17 cytokines in the colon were unaffected by CCI; however, colonic paracellular flux and enteric glial cell GFAP expression were significantly increased. Importantly, Cr infection in chronically-injured mice worsened the brain lesion injury and increased astrocyte- and microglial-mediated inflammation. These experimental studies demonstrate chronic and bidirectional brain-gut interactions after TBI, which may negatively impact late outcomes after brain injury. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Persistent Salmonella enterica serovar Typhimurium Infection Increases the Susceptibility of Mice to Develop Intestinal Inflammation

    Directory of Open Access Journals (Sweden)

    Bárbara M. Schultz

    2018-05-01

    Full Text Available Chronic intestinal inflammations are triggered by genetic and environmental components. However, it remains unclear how specific changes in the microbiota, host immunity, or pathogen exposure could promote the onset and exacerbation of these diseases. Here, we evaluated whether Salmonella enterica serovar Typhimurium (S. Typhimurium infection increases the susceptibility to develop intestinal inflammation in mice. Two mouse models were used to evaluate the impact of S. Typhimurium infection: the chemical induction of colitis by dextran sulfate sodium (DSS and interleukin (IL-10−/− mice, which develop spontaneous intestinal inflammation. We observed that S. Typhimurium infection makes DSS-treated and IL-10−/− mice more susceptible to develop intestinal inflammation. Importantly, this increased susceptibility is associated to the ability of S. Typhimurium to persist in liver and spleen of infected mice, which depends on the virulence proteins secreted by Salmonella Pathogenicity Island 2-encoded type three secretion system (TTSS-2. Although immunization with a live attenuated vaccine resulted in a moderate reduction of the IL-10−/− mice susceptibility to develop intestinal inflammation due to previous S. Typhimurium infection, it did not prevent bacterial persistence. Our results suggest that persistent S. Typhimurium infection may increase the susceptibility of mice to develop inflammation in the intestine, which could be associated with virulence proteins secreted by TTSS-2.

  7. Pronounced susceptibility to infection by Salmonella enterica serovar Typhimurium in mice chronically exposed to lead correlates with a shift to Th2-type immune responses

    International Nuclear Information System (INIS)

    Fernandez-Cabezudo, Maria J.; Ali, Sumaya A.E.; Ullah, Azim; Hasan, Mohammed Y.; Kosanovic, Melita; Fahim, Mohamed A.; Adem, Abdu; Al-Ramadi, Basel K.

    2007-01-01

    Persistent exposure to inorganic lead (Pb) is known to adversely affect the immune system. In the present study, we assessed the effect of chronic Pb exposure on susceptibility to infection by the facultative intracellular pathogen Salmonella enterica serovar Typhimurium. Mice were exposed to 10 mM Pb-acetate in drinking water for ∼ 16 weeks, resulting in a significant level of Pb in the blood (106.2 ± 8.9 μg/dl). Pb exposure rendered mice susceptible to Salmonella infection, manifested by increased bacterial burden in target organs and heightened mortality. Flow cytometric analysis of the splenic cellular composition in normal and Pb-exposed mice revealed no gross alteration in the ratios of B and T lymphocytes or myeloid cells. Similarly, the capacity of B and T cells to upregulate the expression of activation antigens in response to mitogenic or inflammatory stimuli was not hindered by Pb exposure. Analysis of the ability of ex vivo-cultured splenocytes to secrete cytokines demonstrated a marked reduction in IFN-γ and IL-12p40 production associated with Pb exposure. In contrast, secretion of IL-4 by splenocytes of Pb-treated mice was 3- to 3.6-fold higher than in normal mice. The increased capacity to produce IL-4 correlated with a shift in the in vivo anti-Salmonella antibody response from the protective IgG2a isotype to the Th2-induced IgG1 isotype. We conclude that chronic exposure to high levels of Pb results in a state of immunodeficiency which is not due to an overt cytotoxic or immunosuppressive mechanism, but rather is largely caused by a shift in immune responsiveness to Th2-type reactions

  8. ATM facilitates mouse gammaherpesvirus reactivation from myeloid cells during chronic infection.

    Science.gov (United States)

    Kulinski, Joseph M; Darrah, Eric J; Broniowska, Katarzyna A; Mboko, Wadzanai P; Mounce, Bryan C; Malherbe, Laurent P; Corbett, John A; Gauld, Stephen B; Tarakanova, Vera L

    2015-09-01

    Gammaherpesviruses are cancer-associated pathogens that establish life-long infection in most adults. Insufficiency of Ataxia-Telangiectasia mutated (ATM) kinase leads to a poor control of chronic gammaherpesvirus infection via an unknown mechanism that likely involves a suboptimal antiviral response. In contrast to the phenotype in the intact host, ATM facilitates gammaherpesvirus reactivation and replication in vitro. We hypothesized that ATM mediates both pro- and antiviral activities to regulate chronic gammaherpesvirus infection in an immunocompetent host. To test the proposed proviral activity of ATM in vivo, we generated mice with ATM deficiency limited to myeloid cells. Myeloid-specific ATM deficiency attenuated gammaherpesvirus infection during the establishment of viral latency. The results of our study uncover a proviral role of ATM in the context of gammaherpesvirus infection in vivo and support a model where ATM combines pro- and antiviral functions to facilitate both gammaherpesvirus-specific T cell immune response and viral reactivation in vivo. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Hepatitis E virus genotype three infection of human liver chimeric mice as a model for chronic HEV infection

    NARCIS (Netherlands)

    M.D.B. van de Garde (Martijn D.B.); S.D. Pas (Suzan); G. van der Net (Guido); R.A. de Man (Robert); A.D.M.E. Osterhaus (Albert); B.L. Haagmans (Bart); A. Boonstra (Andre); T. Vanwolleghem (Thomas)

    2016-01-01

    textabstractGenotype (gt) 3 hepatitis E virus (HEV) infections are emerging in Western countries. Immunosuppressed patients are at risk of chronic HEV infection and progressive liver damage, but no adequate model system currently mimics this disease course. Here we explore the possibilities of in

  10. Respiratory syncytial virus infections enhance cigarette smoke induced COPD in mice.

    Directory of Open Access Journals (Sweden)

    Robert F Foronjy

    Full Text Available Respiratory syncytial viral (RSV infections are a frequent cause of chronic obstructive pulmonary disease (COPD exacerbations, which are a major factor in disease progression and mortality. RSV is able to evade antiviral defenses to persist in the lungs of COPD patients. Though RSV infection has been identified in COPD, its contribution to cigarette smoke-induced airway inflammation and lung tissue destruction has not been established. Here we examine the long-term effects of cigarette smoke exposure, in combination with monthly RSV infections, on pulmonary inflammation, protease production and remodeling in mice. RSV exposures enhanced the influx of macrophages, neutrophils and lymphocytes to the airways of cigarette smoke exposed C57BL/6J mice. This infiltration of cells was most pronounced around the vasculature and bronchial airways. By itself, RSV caused significant airspace enlargement and fibrosis in mice and these effects were accentuated with concomitant smoke exposure. Combined stimulation with both smoke and RSV synergistically induced cytokine (IL-1α, IL-17, IFN-γ, KC, IL-13, CXCL9, RANTES, MIF and GM-CSF and protease (MMP-2, -8, -12, -13, -16 and cathepsins E, S, W and Z expression. In addition, RSV exposure caused marked apoptosis within the airways of infected mice, which was augmented by cigarette smoke exposure. RSV and smoke exposure also reduced protein phosphatase 2A (PP2A and protein tyrosine phosphates (PTP1B expression and activity. This is significant as these phosphatases counter smoke-induced inflammation and protease expression. Together, these findings show for the first time that recurrent RSV infection markedly enhances inflammation, apoptosis and tissue destruction in smoke-exposed mice. Indeed, these results indicate that preventing RSV transmission and infection has the potential to significantly impact on COPD severity and progression.

  11. HTLV-1 Infection and Neuropathogenesis in the Context of Rag1-/-γc-/- (RAG1-Hu) and BLT Mice.

    Science.gov (United States)

    Ginwala, Rashida; Caruso, Breanna; Khan, Zafar K; Pattekar, Ajinkya; Chew, Glen M; Corley, Michael J; Loonawat, Ronak; Jacobson, Steven; Sreedhar, Sreesha; Ndhlovu, Lishomwa C; Jain, Pooja

    2017-09-01

    To date, the lack of a suitable small animal model has hindered our understanding of Human T-cell lymphotropic virus (HTLV)-1 chronic infection and associated neuropathogenesis defined as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The host immune response plays a critical role in the outcome of HTLV-1 infection, which could be better tested in the context of humanized (hu) mice. Thus, we employ here the Balb/c-Rag1 -/- γc -/- or Rag1 as well as Bone marrow-Liver-Thymic (BLT) mouse models for engraftment of human CD34 + hematopoietic stem cells. Flow cytometry and histological analyses confirmed reconstitution of Rag1 and BLT mice with human immune cells. Following HTLV-1 infection, proviral load (PVL) was detected in the blood of Rag-1 and BLT hu-mice as early as 2 weeks post-infection (wpi) with sustained elevation in the subsequent weeks followed by Tax expression. Additionally, infection was compared between adult and neonatal Rag1 mice with both PVL and Tax expression considerably higher in the adult Rag1 mice as compared to the neonates. Establishment of peripheral infection led to lymphocytic infiltration with concomitant Tax expression and resulting myelin disruption within the central nervous system of infected mice. In addition, up-regulation in the expression of several immune checkpoint mediators such as programmed cell death-1 (PD-1), T-cell Ig and ITIM domain (TIGIT), and T cell Ig and mucin domain-3 protein (Tim-3) were observed on CD8 + T cells in various organs including the CNS of infected hu-mice. Collectively, these studies represent the first attempt to establish HTLV-1 neuropathogenesis in the context of Rag-1 and BLT hu-mice as potential novel tools for understanding HTLV-1 neuropathogenesis and testing of novel therapies such as immune checkpoint blockade in the amelioration of chronic HTLV-1 infection.

  12. EBV CHRONIC INFECTIONS

    Directory of Open Access Journals (Sweden)

    Eligio Pizzigallo

    2010-08-01

    Full Text Available The infection from Epstein-Barr virus (EBV or virus of infectious mononucleosis, together with other herpesviruses’ infections, represents a prototype of persistent viral infections characterized by the property of the latency. Although the reactivations of the latent infection are associated with the resumption of the viral replication and eventually with the “shedding”, it is still not clear if this virus can determine chronic infectious diseases, more or less evolutive. These diseases could include some pathological conditions actually defined as “idiopathic”and characterized by the “viral persistence” as the more credible pathogenetic factor. Among the so-called idiopathic syndromes, the “chronic fatigue syndrome” (CFS aroused a great interest around the eighties of the last century when, just for its relationship with EBV, it was called “chronic mononucleosis” or “chronic EBV infection”. Today CFS, as defined in 1994 by the CDC of Atlanta (USA, really represents a multifactorial syndrome characterized by a chronic course, where reactivation and remission phases alternate, and by a good prognosis. The etiopathogenetic role of EBV is demonstrated only in a well-examined subgroup of patients, while in most of the remaining cases this role should be played by other infectious agents - able to remain in a latent or persistent way in the host – or even by not infectious agents (toxic, neuroendocrine, methabolic, etc.. However, the pathogenetic substrate of the different etiologic forms seems to be the same, much probably represented by the oxidative damage due to the release of pro-inflammatory cytokines as a response to the triggering event (infectious or not infectious. Anyway, recently the scientists turned their’s attention to the genetic predisposition of the subjects affected by the syndrome, so that in the last years the genetic studies, together with those of molecular biology, received a great impulse

  13. Single-epitope DNA vaccination prevents exhaustion and facilitates a broad antiviral CD8+ T cell response during chronic viral infection

    DEFF Research Database (Denmark)

    Bartholdy, Christina; Stryhn, Anette; Christensen, Jan Pravsgaard

    2004-01-01

    Induction of a monospecific antiviral CD8+ T cell response may pose a risk to the host due to the narrow T cell response induced. At the individual level, this may result in selection of CD8+ T cell escape variants, particularly during chronic viral infection. Second, prior immunization toward a ...... with escape variants. These findings underscore that a monospecific vaccine may induce efficient protective immunity given the right set of circumstances....... of DNA vaccines encoding immunodominant epitopes of lymphocytic choriomeningitis virus (LCMV). We analyzed the spectrum of the CD8+ T cell response and the susceptibility to infection in H-2(b) and H-2(d) mice. Priming for a monospecific, CD8+ T cell response did not render mice susceptible to viral...... variants. Thus, vaccinated mice were protected against chronic infection with LCMV, and no evidence indicating biologically relevant viral escape was obtained. In parallel, a broad and sustained CD8+ T cell response was generated upon infection, and in H-2(d) mice epitope spreading was observed. Even after...

  14. Chronic wasting disease prion infection of differentiated neurospheres.

    Science.gov (United States)

    Iwamaru, Yoshifumi; Mathiason, Candace K; Telling, Glenn C; Hoover, Edward A

    2017-07-04

    A possible strategy to develop more diverse cell culture systems permissive to infection with naturally occurring prions is to exploit culture of neurospheres from transgenic mice expressing the normal prion protein (PrP) of the native host species. Accordingly, we developed differentiated neurosphere cultures from the cervid PrP-expressing mice to investigate whether this in vitro system would support replication of non-adapted cervid-origin chronic wasting disease (CWD) prions. Here we report the successful amplification of disease-associated PrP in differentiated neurosphere cultures within 3 weeks after exposure to CWD prions from both white-tailed deer or elk. This neurosphere culture system provides a new in vitro tool that can be used to assess non-adapted CWD prion propagation and transmission.

  15. Hepatitis E virus (HEV) genotype 3 infection of human liver chimeric mice as a model for chronic HEV infection

    NARCIS (Netherlands)

    M.D.B. van de Garde (Martijn D.B.); S.D. Pas (Suzan); Van Der Net, G. (Guido); R.A. de Man (Robert); A.D.M.E. Osterhaus (Albert); B.L. Haagmans (Bart); P.A. Boonstra (André); T. Vanwolleghem (Thomas)

    2016-01-01

    textabstractGenotype 3 (gt3) hepatitis E virus (HEV) infections are emerging in Western countries. Immunosuppressed patients are at risk of chronic HEV infection and progressive liver damage, but no adequate model system currently mimics this disease course. Here we explore the possibilities of in

  16. Follicular helper T cells promote liver pathology in mice during Schistosoma japonicum infection.

    Directory of Open Access Journals (Sweden)

    Xiaojun Chen

    2014-05-01

    Full Text Available Following Schistosoma japonicum (S. japonicum infection, granulomatous responses are induced by parasite eggs trapped in host organs, particular in the liver, during the acute stage of disease. While excessive liver granulomatous responses can lead to more severe fibrosis and circulatory impairment in chronically infected host. However, the exact mechanism of hepatic granuloma formation has remained obscure. In this study, we for the first time showed that follicular helper T (Tfh cells are recruited to the liver to upregulate hepatic granuloma formation and liver injury in S. japonicum-infected mice, and identified a novel function of macrophages in Tfh cell induction. In addition, our results showed that the generation of Tfh cells driven by macrophages is dependent on cell-cell contact and the level of inducible costimulator ligand (ICOSL on macrophages which is regulated by CD40-CD40L signaling. Our findings uncovered a previously unappreciated role for Tfh cells in liver pathology caused by S. japonicum infection in mice.

  17. Impaired immune responses in the lungs of aged mice following influenza infection

    Directory of Open Access Journals (Sweden)

    Toapanta Franklin R

    2009-11-01

    Full Text Available Abstract Background Each year, influenza virus infection causes severe morbidity and mortality, particularly in the most susceptible groups including children, the elderly (>65 years-old and people with chronic respiratory diseases. Among the several factors that contribute to the increased susceptibility in elderly populations are the higher prevalence of chronic diseases (e.g. diabetes and the senescence of the immune system. Methods In this study, aged and adult mice were infected with sublethal doses of influenza virus (A/Puerto Rico/8/1934. Differences in weight loss, morbidity, virus titer and the kinetics of lung infiltration with cells of the innate and adaptive immune responses were analyzed. Additionally, the main cytokines and chemokines produced by these cells were also assayed. Results Compared to adult mice, aged mice had higher morbidity, lost weight more rapidly, and recovered more slowly from infection. There was a delay in the accumulation of granulocytic cells and conventional dendritic cells (cDCs, but not macrophages in the lungs of aged mice compared to adult animals. The delayed infiltration kinetics of APCs in aged animals correlated with alteration in their activation (CD40 expression, which also correlated with a delayed detection of cytokines and chemokines in lung homogenates. This was associated with retarded lung infiltration by natural killer (NK, CD4+ and CD8+ T-cells. Furthermore, the percentage of activated (CD69+ influenza-specific and IL-2 producer CD8+ T-cells was higher in adult mice compared to aged ones. Additionally, activation (CD69+ of adult B-cells was earlier and correlated with a quicker development of neutralizing antibodies in adult animals. Conclusion Overall, alterations in APC priming and activation lead to delayed production of cytokines and chemokines in the lungs that ultimately affected the infiltration of immune cells following influenza infection. This resulted in delayed activation of the

  18. Influence of infection by Toxoplasma gondii on purine levels and E-ADA activity in the brain of mice experimentally infected mice.

    Science.gov (United States)

    Tonin, Alexandre A; Da Silva, Aleksandro S; Casali, Emerson A; Silveira, Stephanie S; Moritz, Cesar E J; Camillo, Giovana; Flores, Mariana M; Fighera, Rafael; Thomé, Gustavo R; Morsch, Vera M; Schetinger, Maria Rosa C; Rue, Mario De La; Vogel, Fernanda S F; Lopes, Sonia T A

    2014-07-01

    The aim of this study was to assess the purine levels and E-ADA activity in the brain of mice (BALB/c) experimentally infected with Toxoplasma gondii. In experiment I (n=24) the mice were infected with RH strain of T. gondii, while in experiment II (n=36) they were infected with strain ME-49 of T. gondii. Our results showed that, for RH strain (acute phase), an increase in both periods in the levels of ATP, ADP, AMP, adenosine, hypoxanthine, xanthine (only on day 6 PI) and uric acid (only on day 6 PI). By the other hand, the RH strain led, on days 4 and 6 PI, to a reduction in the concentration of inosine. ME-49, a cystogenic strain, showed some differences in acute and chronic phase, since on day 6 PI the levels of ATP and ADP were increased, while on day 30 these same nucleotides were reduced. On day 60 PI, ME-49 induced a reduction in the levels of ATP, ADP, AMP, adenosine, inosine and xanthine, while uric acid was increased. A decrease of E-ADA activity was observed in brain on days 4 and 6 PI (RH), and 30 PI (ME-49); however on day 60 PI E-ADA activity was increased for infection by ME-49 strain. Therefore, it was possible to conclude that infection with T. gondii changes the purine levels and the activity of E-ADA in brain, which may be associated with neurological signs commonly observed in this disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Studies on the surface antigenicity and susceptibility to antibody-dependent killing of developing schistosomula using sera from chronically infected mice and mice vaccinated with irradiated cercariae

    International Nuclear Information System (INIS)

    Bickle, Q.D.; Ford, M.J.

    1982-01-01

    Changes in the surface antigenicity and susceptibility to in vitro killing during development of schistosomula of Schistosoma mansoni were studied using serum from chronically infected mice (CIS) and from mice vaccinated with highly irradiated (20 krad) cercariae (VS). Binding of these sera was quantitated by counting the number of P388D 1 cells (a transformed, macrophage-like cell of mouse origin, bearing Fc receptors for IgG) binding to the parasite surface. Compared with schistosomula derived in vitro by mechanical transformation (MS), schistosomula recovered 3 hr after skin penetration in vitro (SS) showed a significant loss in surface binding of CIS. Schistosomula recovered 3 hr after skin penetration in vivo (SRS) showed even less binding, and this trend continued such that parasites recovered from the lungs 5 days after infection (LS) showed only minimal binding, and 10-day-old worms from the portal system showed no significant binding. In contrast, VS, which bound significantly less well to MS than CIS, showed enhanced binding to SS, and in the face of their declining antigenicity with respect to CIS, 3- to 24-hr SRS maintained this raised level of antigenicity. Although there appeared to be a decline in binding of VS thereafter, LS remained antigenic, still binding as many cells as MS did despite the fact that they also expressed host antigens detected usng antisera raised against mouse RBC. In spite of this persistence of VS binding up to the lung stage, resistance to eosinophil-mediated killing in vitro had developed by 48 hr post-infection, and LS were totally resistant to both eosinophil- and C-mediated killing

  20. Alcohol intake alters immune responses and promotes CNS viral persistence in mice.

    Science.gov (United States)

    Loftis, Jennifer M; Taylor, Jonathan; Raué, Hans-Peter; Slifka, Mark K; Huang, Elaine

    2016-10-01

    Chronic hepatitis C virus (HCV) infection leads to progressive liver disease and is associated with a variety of extrahepatic effects, including central nervous system (CNS) damage and neuropsychiatric impairments. Alcohol abuse can exacerbate these adverse effects on brain and behavior, but the molecular mechanisms are not well understood. This study investigated the role of alcohol in regulating viral persistence and CNS immunopathology in mice infected with lymphocytic choriomeningitis virus (LCMV), a model for HCV infections in humans. Female and male BALB/c mice (n=94) were exposed to alcohol (ethanol; EtOH) and water (or water only) using a two-bottle choice paradigm, followed one week later by infection with either LCMV clone 13 (causes chronic infection similar to chronic HCV), LCMV Armstrong (causes acute infection), or vehicle. Mice were monitored for 60days post-infection and continued to receive 24-h access to EtOH and water. Animals infected with LCMV clone 13 drank more EtOH, as compared to those with an acute or no viral infection. Six weeks after infection with LCMV clone 13, mice with EtOH exposure evidenced higher serum viral titers, as compared to mice without EtOH exposure. EtOH intake was also associated with reductions in virus-specific CD8(+) T cell frequencies (particularly CD11a(hi) subsets) and evidence of persistent CNS viremia in chronically infected mice. These findings support the hypothesis that EtOH use and chronic viral infection can result in combined toxic effects accelerating CNS damage and neuropsychiatric dysfunction and suggest that examining the role of EtOH in regulating viral persistence and CNS immunopathology in mice infected with LCMV can lead to a more comprehensive understanding of comorbid alcohol use disorder and chronic viral infection. Published by Elsevier B.V.

  1. Infection of C57BL/6 mice by Trypanosoma musculi modulates host immune responses during Brucella abortus cocolonization.

    Science.gov (United States)

    Lowry, Jake E; Leonhardt, Jack A; Yao, Chaoqun; Belden, E Lee; Andrews, Gerard P

    2014-01-01

    Brucellosis, which results in fetal abortions in domestic and wildlife animal populations, is of major concern in the US and throughout much of the world. The disease, caused by Brucella abortus, poses an economic threat to agriculture-based communities. A moderately efficacious live attenuated vaccine (B. abortus strain RB51) exists. However, even with vaccine use, outbreaks occur. Evidence suggests that elk (Cervus canadensis), a wild host reservoir, are the source of recent outbreaks in domestic cattle herds in Wyoming, USA. Brucella abortus establishes a chronic, persistent infection in elk. The molecular mechanisms allowing the establishment of this persistent infective state are currently unknown. A potential mechanism could be that concurrent pathogen burdens contribute to persistence. In Wyoming, elk are chronically infected with Trypanosoma cervi, which may modulate host responses in a similar manner to that documented for other trypanosomes. To identify any synergistic relationship between the two pathogens, we simulated coinfection in the well-established murine brucellosis model using Trypanosoma musculi and B. abortus S19. Groups of C57BL/6 mice (Mus musculus) were infected with either B. abortus strain 19 (S19) or T. musculi or both. Sera were collected weekly; spleens from euthanized mice were tested to determine bacterial load near the end of normal brucellosis infection. Although changes in bacterial load were observed during the later stages of brucellosis in those mice coinfected with T. musculi, the most significant finding was the suppression of gamma interferon early during the infection along with an increase in interleukin-10 secretion compared with mice infected with either pathogen alone. These results suggest that immune modulatory events occur in the mouse during coinfection and that further experiments are warranted to determine if T. cervi impacts Brucella infection in elk.

  2. IL-22 Defect During Streptococcus pneumoniae Infection Triggers Exacerbation of Chronic Obstructive Pulmonary Disease

    Directory of Open Access Journals (Sweden)

    Muriel Pichavant

    2015-11-01

    Full Text Available Progression of chronic obstructive pulmonary disease (COPD is linked to episodes of exacerbations caused by bacterial infections due to Streptococcus pneumoniae. Our objective was to identify during COPD, factors of susceptibility to bacterial infections among cytokine network and their role in COPD exacerbations. S. pneumoniae was used to sub-lethally challenge mice chronically exposed to air or cigarette smoke (CS and to stimulate peripheral blood mononuclear cells (PBMC from non-smokers, smokers and COPD patients. The immune response and the cytokine production were evaluated. Delayed clearance of the bacteria and stronger lung inflammation observed in infected CS-exposed mice were associated with an altered production of IL-17 and IL-22 by innate immune cells. This defect was related to a reduced production of IL-1β and IL-23 by antigen presenting cells. Importantly, supplementation with recombinant IL-22 restored bacterial clearance in CS-exposed mice and limited lung alteration. In contrast with non-smokers, blood NK and NKT cells from COPD patients failed to increase IL-17 and IL-22 levels in response to S. pneumoniae, in association with a defect in IL-1β and IL-23 secretion. This study identified IL-17 and IL-22 as susceptibility factors in COPD exacerbation. Therefore targeting such cytokines could represent a potent strategy to control COPD exacerbation.

  3. Characterization of in vitro phenotypes of Burkholderia pseudomallei and Burkholderia mallei strains potentially associated with persistent infection in mice.

    Science.gov (United States)

    Bernhards, R C; Cote, C K; Amemiya, K; Waag, D M; Klimko, C P; Worsham, P L; Welkos, S L

    2017-03-01

    Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm), the agents of melioidosis and glanders, respectively, are Tier 1 biothreats. They infect humans and animals, causing disease ranging from acute and fatal to protracted and chronic. Chronic infections are especially challenging to treat, and the identification of in vitro phenotypic markers which signal progression from acute to persistent infection would be extremely valuable. First, a phenotyping strategy was developed employing colony morphotyping, chemical sensitivity testing, macrophage infection, and lipopolysaccharide fingerprint analyses to distinguish Burkholderia strains. Then mouse spleen isolates collected 3-180 days after infection were characterized phenotypically. Isolates from long-term infections often exhibited increased colony morphology differences and altered patterns of antimicrobial sensitivity and macrophage infection. Some of the Bp and Bm persistent infection isolates clearly displayed enhanced virulence in mice. Future studies will evaluate the potential role and significance of these phenotypic markers in signaling the establishment of a chronic infection.

  4. Therapeutic effect of cefozopran (SCE-2787), a new parenteral cephalosporin, against experimental infections in mice.

    Science.gov (United States)

    Iizawa, Y; Okonogi, K; Hayashi, R; Iwahi, T; Yamazaki, T; Imada, A

    1993-01-01

    The therapeutic effect of cefozopran (SCE-2787), a new semisynthetic parenteral cephalosporin, against experimental infections in mice was examined. Cefozopran was more effective than cefpiramide and was as effective as ceftazidime and cefpirome against acute respiratory tract infections caused by Klebsiella pneumoniae DT-S. In the model of chronic respiratory tract infection caused by K. pneumoniae 27, cefozopran was as effective as ceftazidime. The therapeutic effect of cefozopran against urinary tract infections caused by Pseudomonas aeruginosa P9 was superior to that of cefpirome and was equal to those of ceftazidime and cefclidin. In addition, cefozopran was more effective than ceftazidime and was as effective as flomoxef in a thigh muscle infection caused by methicillin-sensitive Staphylococcus aureus 308A-1. Against thigh muscle infections caused by methicillin-resistant S. aureus N133, cefozopran was the most effective agent. The potent therapeutic effect of cefozopran in those experimental infections in mice suggests that it would be effective against respiratory tract, urinary tract, and soft tissue infections caused by a variety of gram-positive and gram-negative bacteria in humans. PMID:8431004

  5. Induction of Type I Interferons by Therapeutic Nanoparticle-Based Vaccination Is Indispensable to Reinforce Cytotoxic CD8+ T Cell Responses During Chronic Retroviral Infection

    Science.gov (United States)

    Knuschke, Torben; Rotan, Olga; Bayer, Wibke; Kollenda, Sebastian; Dickow, Julia; Sutter, Kathrin; Hansen, Wiebke; Dittmer, Ulf; Lang, Karl S.; Epple, Matthias; Buer, Jan; Westendorf, Astrid M.

    2018-01-01

    T cell dysfunction and immunosuppression are characteristic for chronic viral infections and contribute to viral persistence. Overcoming these burdens is the goal of new therapeutic strategies to cure chronic infectious diseases. We recently described that therapeutic vaccination of chronic retrovirus infected mice with a calcium phosphate (CaP) nanoparticle (NP)-based vaccine carrier, functionalized with CpG and viral peptides is able to efficiently reactivate the CD8+ T cell response and improve the eradication of virus infected cells. However, the mechanisms underlying this effect were largely unclear. While type I interferons (IFNs I) are considered to drive T cell exhaustion by persistent immune activation during chronic viral infection, we here describe an indispensable role of IFN I induced by therapeutic vaccination to efficiently reinforce cytotoxic CD8+ T cells (CTL) and improve control of chronic retroviral infection. The induction of IFN I is CpG dependent and leads to significant IFN signaling indicated by upregulation of IFN stimulated genes. By vaccinating chronically retrovirus-infected mice lacking the IFN I receptor (IFNAR−/−) or by blocking IFN I signaling in vivo during therapeutic vaccination, we demonstrate that IFN I signaling is necessary to drive full reactivation of CTLs. Surprisingly, we also identified an impaired suppressive capability of regulatory T cells in the presence of IFNα, which implicates an important role for vaccine-induced IFNα in the regulation of the T cell response during chronic retroviral infection. Our data suggest that inducing IFN I signaling in conjunction with the presentation of viral antigens can reactivate immune functions and reduce viral loads in chronic infections. Therefore, we propose CaP NPs as potential therapeutic tool to treat chronic infections. PMID:29740425

  6. Chronic wasting disease prions are not transmissible to transgenic mice overexpressing human prion protein.

    Science.gov (United States)

    Sandberg, Malin K; Al-Doujaily, Huda; Sigurdson, Christina J; Glatzel, Markus; O'Malley, Catherine; Powell, Caroline; Asante, Emmanuel A; Linehan, Jacqueline M; Brandner, Sebastian; Wadsworth, Jonathan D F; Collinge, John

    2010-10-01

    Chronic wasting disease (CWD) is a prion disease that affects free-ranging and captive cervids, including mule deer, white-tailed deer, Rocky Mountain elk and moose. CWD-infected cervids have been reported in 14 USA states, two Canadian provinces and in South Korea. The possibility of a zoonotic transmission of CWD prions via diet is of particular concern in North America where hunting of cervids is a popular sport. To investigate the potential public health risks posed by CWD prions, we have investigated whether intracerebral inoculation of brain and spinal cord from CWD-infected mule deer transmits prion infection to transgenic mice overexpressing human prion protein with methionine or valine at polymorphic residue 129. These transgenic mice have been utilized in extensive transmission studies of human and animal prion disease and are susceptible to BSE and vCJD prions, allowing comparison with CWD. Here, we show that these mice proved entirely resistant to infection with mule deer CWD prions arguing that the transmission barrier associated with this prion strain/host combination is greater than that observed with classical BSE prions. However, it is possible that CWD may be caused by multiple prion strains. Further studies will be required to evaluate the transmission properties of distinct cervid prion strains as they are characterized.

  7. EBV CHRONIC INFECTIONS

    Directory of Open Access Journals (Sweden)

    Delia Racciatti

    2010-02-01

    Full Text Available

    The infection from Epstein-Barr virus (EBV or virus of infectious mononucleosis, together with other herpesviruses’ infections, represents a prototype of persistent viral infections characterized by the property of the latency. Although the reactivations of the latent infection are associated with the resumption of the viral replication and eventually with the “shedding”, it is still not clear if this virus can determine chronic infectious diseases, more or less evolutive. These diseases could include some pathological conditions actually defined as “idiopathic”and characterized by the “viral persistence” as the more credible pathogenetic factor. Among the so-called idiopathic syndromes, the “chronic fatigue syndrome” (CFS aroused a great interest around the eighties of the last century when, just for its relationship with EBV, it was called “chronic mononucleosis” or “chronic EBV infection”.

    Today CFS, as defined in 1994 by the CDC of Atlanta (USA, really represents a multifactorial syndrome characterized by a chronic course, where reactivation and remission phases alternate, and by a good prognosis

  8. Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry in mice.

    Science.gov (United States)

    Bercik, Premysl; Verdu, Elena F; Foster, Jane A; Macri, Joseph; Potter, Murray; Huang, Xiaxing; Malinowski, Paul; Jackson, Wendy; Blennerhassett, Patricia; Neufeld, Karen A; Lu, Jun; Khan, Waliul I; Corthesy-Theulaz, Irene; Cherbut, Christine; Bergonzelli, Gabriela E; Collins, Stephen M

    2010-12-01

    Clinical and preclinical studies have associated gastrointestinal inflammation and infection with altered behavior. We investigated whether chronic gut inflammation alters behavior and brain biochemistry and examined underlying mechanisms. AKR mice were infected with the noninvasive parasite Trichuris muris and given etanercept, budesonide, or specific probiotics. Subdiaphragmatic vagotomy was performed in a subgroup of mice before infection. Gastrointestinal inflammation was assessed by histology and quantification of myeloperoxidase activity. Serum proteins were measured by proteomic analysis, circulating cytokines were measured by fluorescence activated cell sorting array, and serum tryptophan and kynurenine were measured by liquid chromatography. Behavior was assessed using light/dark preference and step-down tests. In situ hybridization was used to assess brain-derived neurotrophic factor (BDNF) expression in the brain. T muris caused mild to moderate colonic inflammation and anxiety-like behavior that was associated with decreased hippocampal BDNF messenger RNA (mRNA). Circulating tumor necrosis factor-α and interferon-γ, as well as the kynurenine and kynurenine/tryptophan ratio, were increased. Proteomic analysis showed altered levels of several proteins related to inflammation and neural function. Administration of etanercept, and to a lesser degree of budesonide, normalized behavior, reduced cytokine and kynurenine levels, but did not influence BDNF expression. The probiotic Bifidobacterium longum normalized behavior and BDNF mRNA but did not affect cytokine or kynurenine levels. Anxiety-like behavior was present in infected mice after vagotomy. Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry, which can be normalized by inflammation-dependent and -independent mechanisms, neither of which requires the integrity of the vagus nerve. Copyright © 2010 AGA Institute. Published by Elsevier Inc

  9. Chronic infections in hip arthroplasties

    DEFF Research Database (Denmark)

    Lange, Jeppe; Troelsen, Anders; Thomsen, Reimar W

    2012-01-01

    Two-stage revision is regarded by many as the best treatment of chronic infection in hip arthroplasties. Some international reports, however, have advocated one-stage revision. No systematic review or meta-analysis has ever compared the risk of reinfection following one-stage and two-stage revisi......Two-stage revision is regarded by many as the best treatment of chronic infection in hip arthroplasties. Some international reports, however, have advocated one-stage revision. No systematic review or meta-analysis has ever compared the risk of reinfection following one-stage and two......-stage revisions for chronic infection in hip arthroplasties....

  10. Induction of Type I Interferons by Therapeutic Nanoparticle-Based Vaccination Is Indispensable to Reinforce Cytotoxic CD8+ T Cell Responses During Chronic Retroviral Infection

    Directory of Open Access Journals (Sweden)

    Torben Knuschke

    2018-04-01

    Full Text Available T cell dysfunction and immunosuppression are characteristic for chronic viral infections and contribute to viral persistence. Overcoming these burdens is the goal of new therapeutic strategies to cure chronic infectious diseases. We recently described that therapeutic vaccination of chronic retrovirus infected mice with a calcium phosphate (CaP nanoparticle (NP-based vaccine carrier, functionalized with CpG and viral peptides is able to efficiently reactivate the CD8+ T cell response and improve the eradication of virus infected cells. However, the mechanisms underlying this effect were largely unclear. While type I interferons (IFNs I are considered to drive T cell exhaustion by persistent immune activation during chronic viral infection, we here describe an indispensable role of IFN I induced by therapeutic vaccination to efficiently reinforce cytotoxic CD8+ T cells (CTL and improve control of chronic retroviral infection. The induction of IFN I is CpG dependent and leads to significant IFN signaling indicated by upregulation of IFN stimulated genes. By vaccinating chronically retrovirus-infected mice lacking the IFN I receptor (IFNAR−/− or by blocking IFN I signaling in vivo during therapeutic vaccination, we demonstrate that IFN I signaling is necessary to drive full reactivation of CTLs. Surprisingly, we also identified an impaired suppressive capability of regulatory T cells in the presence of IFNα, which implicates an important role for vaccine-induced IFNα in the regulation of the T cell response during chronic retroviral infection. Our data suggest that inducing IFN I signaling in conjunction with the presentation of viral antigens can reactivate immune functions and reduce viral loads in chronic infections. Therefore, we propose CaP NPs as potential therapeutic tool to treat chronic infections.

  11. Anti-gluten immune response following Toxoplasma gondii infection in mice.

    Directory of Open Access Journals (Sweden)

    Emily G Severance

    Full Text Available Gluten sensitivity may affect disease pathogenesis in a subset of individuals who have schizophrenia, bipolar disorder or autism. Exposure to Toxoplasma gondii is a known risk factor for the development of schizophrenia, presumably through a direct pathological effect of the parasite on brain and behavior. A co-association of antibodies to wheat gluten and to T. gondii in individuals with schizophrenia was recently uncovered, suggesting a coordinated gastrointestinal means by which T. gondii and dietary gluten might generate an immune response. Here, we evaluated the connection between these infectious- and food-based antigens in mouse models. BALB/c mice receiving a standard wheat-based rodent chow were infected with T. gondii via intraperitoneal, peroral and prenatal exposure methods. Significant increases in the levels of anti-gluten IgG were documented in all infected mice and in offspring from chronically infected dams compared to uninfected controls (repetitive measures ANOVAs, two-tailed t-tests, all p≤0.00001. Activation of the complement system accompanied this immune response (p≤0.002-0.00001. Perorally-infected females showed higher levels of anti-gluten IgG than males (p≤0.009 indicating that T. gondii-generated gastrointestinal infection led to a significant anti-gluten immune response in a sex-dependent manner. These findings support a gastrointestinal basis by which two risk factors for schizophrenia, T. gondii infection and sensitivity to dietary gluten, might be connected to produce the immune activation that is becoming an increasingly recognized pathology of psychiatric disorders.

  12. In Situ Microscopy Analysis Reveals Local Innate Immune Response Developed around Brucella Infected Cells in Resistant and Susceptible Mice

    Science.gov (United States)

    Copin, Richard; Vitry, Marie-Alice; Hanot Mambres, Delphine; Machelart, Arnaud; De Trez, Carl; Vanderwinden, Jean-Marie; Magez, Stefan; Akira, Shizuo; Ryffel, Bernhard; Carlier, Yves; Letesson, Jean-Jacques; Muraille, Eric

    2012-01-01

    Brucella are facultative intracellular bacteria that chronically infect humans and animals causing brucellosis. Brucella are able to invade and replicate in a broad range of cell lines in vitro, however the cells supporting bacterial growth in vivo are largely unknown. In order to identify these, we used a Brucella melitensis strain stably expressing mCherry fluorescent protein to determine the phenotype of infected cells in spleen and liver, two major sites of B. melitensis growth in mice. In both tissues, the majority of primary infected cells expressed the F4/80 myeloid marker. The peak of infection correlated with granuloma development. These structures were mainly composed of CD11b+ F4/80+ MHC-II+ cells expressing iNOS/NOS2 enzyme. A fraction of these cells also expressed CD11c marker and appeared similar to inflammatory dendritic cells (DCs). Analysis of genetically deficient mice revealed that differentiation of iNOS+ inflammatory DC, granuloma formation and control of bacterial growth were deeply affected by the absence of MyD88, IL-12p35 and IFN-γ molecules. During chronic phase of infection in susceptible mice, we identified a particular subset of DC expressing both CD11c and CD205, serving as a reservoir for the bacteria. Taken together, our results describe the cellular nature of immune effectors involved during Brucella infection and reveal a previously unappreciated role for DC subsets, both as effectors and reservoir cells, in the pathogenesis of brucellosis. PMID:22479178

  13. TRPV1 and the MCP-1/CCR2 Axis Modulate Post-UTI Chronic Pain.

    Science.gov (United States)

    Rosen, John M; Yaggie, Ryan E; Woida, Patrick J; Miller, Richard J; Schaeffer, Anthony J; Klumpp, David J

    2018-05-08

    The etiology of chronic pelvic pain syndromes remains unknown. In a murine urinary tract infection (UTI) model, lipopolysaccharide of uropathogenic E. coli and its receptor TLR4 are required for post-UTI chronic pain development. However, downstream mechanisms of post-UTI chronic pelvic pain remain unclear. Because the TRPV1 and MCP-1/CCR2 pathways are implicated in chronic neuropathic pain, we explored their role in post-UTI chronic pain. Mice were infected with the E. coli strain SΦ874, known to produce chronic allodynia, and treated with the TRPV1 antagonist capsazepine. Mice treated with capsazepine at the time of SΦ874 infection failed to develop chronic allodynia, whereas capsazepine treatment of mice at two weeks following SΦ874 infection did not reduce chronic allodynia. TRPV1-deficient mice did not develop chronic allodynia either. Similar results were found using novelty-suppressed feeding (NSF) to assess depressive behavior associated with neuropathic pain. Imaging of reporter mice also revealed induction of MCP-1 and CCR2 expression in sacral dorsal root ganglia following SΦ874 infection. Treatment with a CCR2 receptor antagonist at two weeks post-infection reduced chronic allodynia. Taken together, these results suggest that TRPV1 has a role in the establishment of post-UTI chronic pain, and CCR2 has a role in maintenance of post-UTI chronic pain.

  14. IL-23 p19 knockout mice exhibit minimal defects in responses to primary and secondary infection with Francisella tularensis LVS.

    Directory of Open Access Journals (Sweden)

    Sherry L Kurtz

    Full Text Available Our laboratory's investigations into mechanisms of protective immunity against Francisella tularensis Live Vaccine Strain (LVS have uncovered mediators important in host defense against primary infection, as well as those correlated with successful vaccination. One such potential correlate was IL-12p40, a pleiotropic cytokine that promotes Th1 T cell function as part of IL-12p70. LVS-infected IL-12p40 deficient knockout (KO mice maintain a chronic infection, but IL-12p35 KO mice clear LVS infection; thus the role that IL-12p40 plays in immunity to LVS is independent of the IL-12p70 heterodimer. IL-12p40 can also partner with IL-23p19 to create the heterodimeric cytokine IL-23. Here, we directly tested the role of IL-23 in LVS resistance, and found IL-23 to be largely dispensable for immunity to LVS following intradermal or intranasal infection. IL-23p19 KO splenocytes were fully competent in controlling intramacrophage LVS replication in an in vitro overlay assay. Further, antibody responses in IL-23p19 KO mice were similar to those of normal wild type mice after LVS infection. IL-23p19 KO mice or normal wild type mice that survived primary LVS infection survived maximal doses of LVS secondary challenge. Thus p40 has a novel role in clearance of LVS infection that is unrelated to either IL-12 or IL-23.

  15. Pectin-Derived Acidic Oligosaccharides Improve the Outcome of Pseudomonas aeruginosa Lung Infection in C57BL/6 Mice.

    Directory of Open Access Journals (Sweden)

    Henry Bernard

    Full Text Available The administration of prebiotics as oligosaccharides (OS, by acting on intestinal microbiota, could modulate the immune and inflammatory response and represent a new strategy to improve the outcome of bacterial infection. The aim of this study was to determine whether pectin-derived acidic oligosaccharides (pAOS could modulate the outcome of pulmonary P. aeruginosa (PA infection in C57BL/6 mice, which develop a Th1 response to PA lung infection. Mice were randomized for 5 weeks to consume a control or a 5% pAOS diet and chronically infected by PA. Resistance to a second PA infection was also analyzed by reinfecting the surviving mice 2 weeks after the first infection. Compared with control mice, mice fed pAOS had reduced mortality (P<0.05. This improvement correlated with a better control of the inflammatory response with a lower neutrophil count on day 1 (P<0.05, a sustained neutrophil and macrophage recruitment on days 2 and 3 (P<0.01 a greater and sustained IL-10 release in lung (P<0.05 and a reduction of the Th1 response and M1 activation with a lower IFN-γ/IL-4 (P<0.01 and nos2/arg1 (P<0.05 ratios. These results coincided with a modulation of the intestinal microbiota as shown by an increased butyric acid concentration in feces (P<0.05. Moreover, pAOS decreased the bacterial load (P<0.01 in mice reinfected 2 weeks after the first infection, suggesting that pAOS could reduce pulmonary exacerbations. In conclusion, pAOS improved the outcome of PA infection in C57BL/6 mice by modulating the intestinal microbiota and the inflammatory and immune responses.

  16. Mutagenicity of nicotine in Schistosoma mansoni - infected mice ...

    African Journals Online (AJOL)

    Analysis of meiotic chromosomes showed significant elevation in the Schistosoma-infected mice. Administration of nicotine to infected mice substantially increased the percentages of micronucleated cells and total CAs. The percentage of chromosomal abnormalities in spermatocyte metaphase-I cells increased significantly ...

  17. The Dynamics of Treg/Th17 and the Imbalance of Treg/Th17 in Clonorchis sinensis-Infected Mice

    Science.gov (United States)

    Hua, Hui; Li, Bo; Zhang, Bo; Yu, Qian; Li, Xiang-Yang; Liu, Ying; Pan, Wei; Liu, Xiang-Ye; Tang, Ren-Xian; Zheng, Kui-Yang

    2015-01-01

    Clonorchiasis, caused by the liver fluke Clonorchis sinensis, is a chronic parasitic infection regulated by T cell subsets. An imbalance of CD4+CD25+ Foxp3+regulatory T (Treg) and interleukin (IL)-17-secreting T cells (Th17) may control inflammation and play an important role in the pathogenesis of immune evasion. In the present study, we assessed the dynamics of Treg/Th17 and determined whether the Treg/Th17 ratio is altered in C. sinensis-infected mice. The results showed that the percentages of splenic Treg cells in CD4+ T cells were suppressed on day 14 post-infection (PI) but increased on day 56 PI, while Th17 cells were increased on day 56 PI compared with normal control (NC) mice. The Treg/Th17 ratio steadily increased from day 28 to day 56 PI. The hepatic levels of their specific transcription factors (Foxp3 for Treg and RORγt for Th17) were increased in C. sinensis-infected mice from day 14 to 56 PI, and significantly higher than those in NC mice. Meanwhile, serum levels of IL-2 and IL-17 were profoundly increased in C. sinensis-infected mice throughout the experiment; while the concentrations of IL-6 and transforming growth factor β1 (TGF-β1) peaked on day 14 PI, but then decreased on day 28 and 56 PI. Our results provide the first evidence of an increased Treg/Th17 ratio in C. sinensis-infected mice, suggesting that a Treg/Th17 imbalance may play a role in disease outcomes of clonorchiasis. PMID:26599407

  18. Chronic inflammation induces telomere dysfunction and accelerates ageing in mice

    NARCIS (Netherlands)

    Jurk, Diana; Wilson, Caroline; Passos, Joao F.; Oakley, Fiona; Correia-Melo, Clara; Greaves, Laura; Saretzki, Gabriele; Fox, Chris; Lawless, Conor; Anderson, Rhys; Hewitt, Graeme; Pender, Sylvia L. F.; Fullard, Nicola; Nelson, Glyn; Mann, Jelena; van de Sluis, Bart; Mann, Derek A.; von Zglinicki, Thomas

    Chronic inflammation is associated with normal and pathological ageing. Here we show that chronic, progressive low-grade inflammation induced by knockout of the nfkb1 subunit of the transcription factor NF-kappa B induces premature ageing in mice. We also show that these mice have reduced

  19. Local immune response to primary infection and re-infection by Clonorchis sinensis in FVB mice.

    Science.gov (United States)

    Kim, Eun-Min; Yu, Hak Sun; Jin, Yan; Choi, Min-Ho; Bae, Young Mee; Hong, Sung-Tae

    2017-08-01

    Although Clonorchis sinensis lives in the bile duct, few studies have investigated the local immune response in the liver and bile duct. To investigate the local immune response to C. sinensis, we investigated the activation and recruitment of various immune cells and cytokine levels in the liver and bile duct lymph nodes (BLN) in FVB mice after primary infection and re-infection. Male 4-week-old FVB mice were divided into 6 experimental groups: uninfected controls, primary infection lasting 1week (PI 1w), primary infection lasting 4weeks (PI 4w), praziquantel treatment after PI 4w (Tx), re-infection lasting 1week after Tx (RI 1w), and re-infection lasting 4weeks after Tx (RI 4w). Recovery rates were 80.0% and 73.0% in PI 1w and PI 4w mice, respectively, but significantly decreased during re-infection to 26.6% in RI 1w and 13.3% in RI 4w. This result suggested that the mice were resistant to re-infection. In the liver, Kupffer cells were augmented 70-fold in PI 1w mice (Psinensis-specific IgG1 and IgG2a strongly increased in RI 1w mice. Secretion of C. sinensis-specific IgE reached a plateau at 4weeks after primary infection, and remained elevated in all infected groups. In conclusion, during infection with C. sinensis, Kupffer cells likely act as antigen-presenting cells, stimulating the Th2 cytokine production system. Copyright © 2016. Published by Elsevier B.V.

  20. Lactobacillus paracasei feeding improves the control of secondary experimental meningococcal infection in flu-infected mice.

    Science.gov (United States)

    Belkacem, Nouria; Bourdet-Sicard, Raphaëlle; Taha, Muhamed-Kkeir

    2018-04-10

    The use of probiotics to improve anti-microbial defence, such as for influenza infections, is increasingly recommended. However, no data are available on the effect of probiotics on flu-associated secondary bacterial infections. There is strong evidence of a spatiotemporal association between influenza virus infection and invasive Neisseria meningitidis. We thus investigated the effect of feeding mice Lactobacillus paracasei CNCM I-1518 in a mouse model of sequential influenza-meningococcal infection. We intranasally infected BALB/c mice with a strain of influenza A virus (IAV) H3N2 that was first adapted to mice. Seven days later, a secondary bacterial infection was induced by intranasal administration of bioluminescent N. meningitidis. During the experiment, mice orally received either L. paracasei CNCM I-1518 or PBS as a control. The effect of L. paracasei administration on secondary bacterial infection by N. meningitidis was evaluated. Oral consumption of L. paracasei CNCM I-1518 reduced the weight loss of infected mice and lowered the bioluminescent signal of infecting meningococci. This improvement was associated with higher recruitment of inflammatory myeloid cells, such as interstitial monocytes and dendritic cells, to the lungs. Our data highlight the role of the gut-lung axis. L. paracasei CNCM I-1518 may boost the defence against IAV infection and secondary bacterial infection, which should be further studied and validated in clinical trials.

  1. Chronic Exposure to Subtherapeutic Antibiotics Aggravates Ischemic Stroke Outcome in Mice

    Directory of Open Access Journals (Sweden)

    Xiao-Hui Dong

    2017-10-01

    Full Text Available Subtherapeutic antibiotics have been widely used in agriculture since the 1950s, which can be accumulated in human body through various approaches and may have long-term consequences. However, there is limited information about the link between chronic subtherapeutic antibiotic exposure and the outcome of ischemic brain injury. Here we showed that long-term treatment with subtherapeutic chlortetracycline, penicillin or vancomycin, which were widely used in agriculture approved by US Food and Drug Administration (FDA, could impair EPC functions, reduce ischemic brain angiogenesis and aggravate cerebral ischemic injury and long-term stroke outcomes in mice. In addition, transplantated EPCs from chronic antibiotic-treated mice showed a lower therapeutic effect on cerebral ischemic injury reduction and local angiogenesis promotion compared to those from control mice, and EPCs from the donor animals could integrate into the recipient ischemic brain in mice. Furthermore, transplanted EPCs might exert paracrine effects on cerebral ischemic injury reduction in mice, which could be impaired by chronic antibiotic exposure. In conclusion, chronic subtherapeutic antibiotic exposure aggravated cerebral ischemic injury in mice, which might be partly attributed to the impairment of both EPC-mediated angiogenesis and EPCs' paracrine effects. These findings reveal a previously unrecognized impact of chronic subtherapeutic antibiotic exposure on ischemic injury.

  2. Sarcocystis neurona infection in gamma interferon gene knockout (KO) mice: comparative infectivity of sporocysts in two strains of KO mice, effect of trypsin digestion on merozoite viability, and infectivity of bradyzoites to KO mice and cell culture.

    Science.gov (United States)

    Dubey, J P; Sundar, N; Kwok, O C H; Saville, W J A

    2013-09-01

    The protozoan Sarcocystis neurona is the primary cause of Equine Protozoal Myeloencephalitis (EPM). EPM or EPM-like illness has been reported in horses, sea otters, and several other mammals. The gamma interferon gene knockout (KO) mouse is often used as a model to study biology and discovery of new therapies against S. neurona because it is difficult to induce clinical EPM in other hosts, including horses. In the present study, infectivity of three life cycle stages (merozoites, bradyzoites, sporozoites) to KO mice and cell culture was studied. Two strains of KO mice (C57-black, and BALB/c-derived, referred here as black or white) were inoculated orally graded doses of S. neurona sporocysts; 12 sporocysts were infective to both strains of mice and all infected mice died or became ill within 70 days post-inoculation. Although there was no difference in infectivity of sporocysts to the two strains of KO mice, the disease was more severe in black mice. S. neurona bradyzoites were not infectious to KO mice and cell culture. S. neurona merozoites survived 120 min incubation in 0.25% trypsin, indicating that trypsin digestion can be used to recover S. neurona from tissues of acutely infected animals. Published by Elsevier B.V.

  3. Effects of Active Mastication on Chronic Stress-Induced Bone Loss in Mice.

    Science.gov (United States)

    Azuma, Kagaku; Furuzawa, Manabu; Fujiwara, Shu; Yamada, Kumiko; Kubo, Kin-ya

    2015-01-01

    Chronic psychologic stress increases corticosterone levels, which decreases bone density. Active mastication or chewing attenuates stress-induced increases in corticosterone. We evaluated whether active mastication attenuates chronic stress-induced bone loss in mice. Male C57BL/6 (B6) mice were randomly divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube (60 min, 2x/day, 4 weeks). The stress/chewing group was given a wooden stick to chew during the experimental period. Quantitative micro-computed tomography, histologic analysis, and biochemical markers were used to evaluate the bone response. The stress/chewing group exhibited significantly attenuated stress-induced increases in serum corticosterone levels, suppressed bone formation, enhanced bone resorption, and decreased trabecular bone mass in the vertebrae and distal femurs, compared with mice in the stress group. Active mastication during exposure to chronic stress alleviated chronic stress-induced bone density loss in B6 mice. Active mastication during chronic psychologic stress may thus be an effective strategy to prevent and/or treat chronic stress-related osteopenia.

  4. Humoral immunity through immunoglobulin M protects mice from an experimental actinomycetoma infection by Nocardia brasiliensis.

    Science.gov (United States)

    Salinas-Carmona, Mario C; Pérez-Rivera, Isabel

    2004-10-01

    An experimental model of infection with Nocardia brasiliensis, used as an example of a facultative intracellular pathogen, was tested. N. brasiliensis was injected into the rear foot pads of BALB/c mice to establish an infection. Within 30 days, infected animals developed a chronic actinomycetoma infection. Batch cultures of N. brasiliensis were used to purify P61, P38, and P24 antigens; P61 is a catalase, and P38 is a protease with strong caseinolytic activity. Active and passive immunizations of BALB/c mice with these three purified soluble antigens were studied. Protection was demonstrated for actively immunized mice. However, immunity lasted only 30 days. Other groups of immunized mice were bled at different times, and their sera were passively transferred to naive recipients that were then infected with N. brasiliensis. Sera collected 5, 6, and 7 days after donor immunization conferred complete, long-lasting protection. The protective effect of passive immunity decreased when sera were collected 2 weeks after donor immunization. However, neither the early sera (1-, 2-, and 3-day sera) nor the later sera (30- or 45-day sera) prevented the infection. Hyperimmune sera with the highest levels of immunoglobulin G (IgG) to N. brasiliensis antigens did not protect at all. The antigens tested induced two IgM peaks. The first peak was present 3 days after immunization but was not antigen specific and did not transfer protection. The second peak was evident 7 days after immunization, was an IgM response, was antigen specific, and conferred protection. This results clearly demonstrate that IgM antibodies protect the host against a facultative intracellular bacterium.

  5. The Dynamics of Treg/Th17 and the Imbalance of Treg/Th17 in Clonorchis sinensis-Infected Mice.

    Directory of Open Access Journals (Sweden)

    Chao Yan

    Full Text Available Clonorchiasis, caused by the liver fluke Clonorchis sinensis, is a chronic parasitic infection regulated by T cell subsets. An imbalance of CD4+CD25+ Foxp3+regulatory T (Treg and interleukin (IL-17-secreting T cells (Th17 may control inflammation and play an important role in the pathogenesis of immune evasion. In the present study, we assessed the dynamics of Treg/Th17 and determined whether the Treg/Th17 ratio is altered in C. sinensis-infected mice. The results showed that the percentages of splenic Treg cells in CD4+ T cells were suppressed on day 14 post-infection (PI but increased on day 56 PI, while Th17 cells were increased on day 56 PI compared with normal control (NC mice. The Treg/Th17 ratio steadily increased from day 28 to day 56 PI. The hepatic levels of their specific transcription factors (Foxp3 for Treg and RORγt for Th17 were increased in C. sinensis-infected mice from day 14 to 56 PI, and significantly higher than those in NC mice. Meanwhile, serum levels of IL-2 and IL-17 were profoundly increased in C. sinensis-infected mice throughout the experiment; while the concentrations of IL-6 and transforming growth factor β1 (TGF-β1 peaked on day 14 PI, but then decreased on day 28 and 56 PI. Our results provide the first evidence of an increased Treg/Th17 ratio in C. sinensis-infected mice, suggesting that a Treg/Th17 imbalance may play a role in disease outcomes of clonorchiasis.

  6. Poliomyelitis in MuLV-infected ICR-SCID mice after injection of basement membrane matrix contaminated with lactate dehydrogenase-elevating virus.

    Science.gov (United States)

    Carlson Scholz, Jodi A; Garg, Rohit; Compton, Susan R; Allore, Heather G; Zeiss, Caroline J; Uchio, Edward M

    2011-10-01

    The arterivirus lactate dehydrogenase-elevating virus (LDV) causes life-long viremia in mice. Although LDV infection generally does not cause disease, infected mice that are homozygous for the Fv1(n) allele are prone to develop poliomyelitis when immunosuppressed, a condition known as age-dependent poliomyelitis. The development of age-dependent poliomyelitis requires coinfection with endogenous murine leukemia virus. Even though LDV is a common contaminant of transplantable tumors, clinical signs of poliomyelitis after inadvertent exposure to LDV have not been described in recent literature. In addition, LDV-induced poliomyelitis has not been reported in SCID or ICR mice. Here we describe the occurrence of poliomyelitis in ICR-SCID mice resulting from injection of LDV-contaminated basement membrane matrix. After exposure to LDV, a subset of mice presented with clinical signs including paresis, which was associated with atrophy of the hindlimb musculature, and tachypnea; in addition, some mice died suddenly with or without premonitory signs. Mice presenting within the first 6 mo after infection had regions of spongiosis, neuronal necrosis and astrocytosis of the ventral spinal cord, and less commonly, brainstem. Axonal degeneration of ventral roots prevailed in more chronically infected mice. LDV was identified by RT-PCR in 12 of 15 mice with typical neuropathology; positive antiLDV immunolabeling was identified in all PCR-positive animals (n = 7) tested. Three of 8 mice with neuropathology but no clinical signs were LDV negative by RT-PCR. RT-PCR yielded murine leukemia virus in spinal cords of all mice tested, regardless of clinical presentation or neuropathology.

  7. Isolated Lactobacillus chronic prosthetic knee infection.

    Science.gov (United States)

    Bennett, David M; Shekhel, Tatyana; Radelet, Matt; Miller, Michael D

    2014-01-01

    Lactobacillus is a gram-positive rod bacteria found primarily in the gastrointestinal and female genital tracts. Prosthetic infections in implants are being increasingly reported. The authors present a case of a 58-year-old patient with Lactobacillus septic prosthetic knee joint infection. To the authors’ knowledge, this is the first reported case of chronic prosthetic knee infection with isolated Lactobacillus species. Lactobacillus has been most commonly implicated with bacteremia and endocarditis and rarely with pneumonia, meningitis, and endovascular infection, and a vast majority of the cases are reported in immunocompromised patients. In the current case, diabetes mellitus, hepatitis, malnutrition, anemia, and liver failure were comorbid conditions, placing the patient at increased risk of infection. The findings suggest that further case series are necessary to establish the significance of Lactobacillus as an etiologic agent in chronic low-virulence, and potentially vancomycin-resistant, prosthetic joint infection. The need also exists for further research aimed at the risk of prosthetic joint infection with oral intake of certain probiotic foods and supplements. The goal of this case report is to bring to light the potential of this organism to be a cause of subtle chronic prosthetic joint infection.

  8. Effect of chronic pain on fentanyl self-administration in mice.

    Directory of Open Access Journals (Sweden)

    Carrie L Wade

    Full Text Available The development of opioid addiction in subjects with established chronic pain is an area that is poorly understood. It is critically important to clearly understand the neurobiology associated with propensity toward conversion to addiction under conditions of chronic pain. To pose the question whether the presence of chronic pain influences motivation to self-administer opioids for reward, we applied a combination of rodent models of chronic mechanical hyperalgesia and opioid self-administration. We studied fentanyl self-administration in mice under three conditions that induce chronic mechanical hyperalgesia: inflammation, peripheral nerve injury, and repeated chemotherapeutic injections. Responding for fentanyl was compared among these conditions and their respective standard controls (naïve condition, vehicle injection or sham surgery. Acquisition of fentanyl self-administration behavior was reduced or absent in all three conditions of chronic hyperalgesia relative to control mice with normal sensory thresholds. To control for potential impairment in ability to learn the lever-pressing behavior or perform the associated motor tasks, all three groups were evaluated for acquisition of food-maintained responding. In contrast to the opioid, chronic hyperalgesia did not interfere with the reinforcing effect of food. These studies indicate that the establishment of chronic hyperalgesia is associated with reduced or ablated motivation to seek opioid reward in mice.

  9. Impaired Subset Progression and Polyfunctionality of T Cells in Mice Exposed to Methamphetamine during Chronic LCMV Infection.

    Science.gov (United States)

    Sriram, Uma; Hill, Beth L; Cenna, Jonathan M; Gofman, Larisa; Fernandes, Nicole C; Haldar, Bijayesh; Potula, Raghava

    2016-01-01

    Methamphetamine (METH) is a widely used psychostimulant that severely impacts the host's innate and adaptive immune systems and has profound immunological implications. T cells play a critical role in orchestrating immune responses. We have shown recently how chronic exposure to METH affects T cell activation using a murine model of lymphocytic choriomeningitis virus (LCMV) infection. Using the TriCOM (trinary state combinations) feature of GemStone™ to study the polyfunctionality of T cells, we have analyzed how METH affected the cytokine production pattern over the course of chronic LCMV infection. Furthermore, we have studied in detail the effects of METH on splenic T cell functions, such as cytokine production and degranulation, and how they regulate each other. We used the Probability State Modeling (PSM) program to visualize the differentiation of effector/memory T cell subsets during LCMV infection and analyze the effects of METH on T cell subset progression. We recently demonstrated that METH increased PD-1 expression on T cells during viral infection. In this study, we further analyzed the impact of PD-1 expression on T cell functional markers as well as its expression in the effector/memory subsets. Overall, our study indicates that analyzing polyfunctionality of T cells can provide additional insight into T cell effector functions. Analysis of T cell heterogeneity is important to highlight changes in the evolution of memory/effector functions during chronic viral infections. Our study also highlights the impact of METH on PD-1 expression and its consequences on T cell responses.

  10. An unusual renal manifestation of chronic HBV infection.

    Science.gov (United States)

    Aravindan, Ananthakrishnapuram; Yong, Jim; Killingsworth, Murray; Strasser, Simone; Suranyi, Michael

    2010-08-01

    Hepatitis B viral infection is usually a self-limiting disease in immunocompetent individuals. Chronic infection can be seen in up to 5% of infected patients. Renal manifestations of chronic HBV infection are usually glomerular. We describe here an uncommon presentation of a patient with chronic HBV infection with very high viral load and rapidly progressive renal failure. Renal biopsy showed features of tubulointerstitial nephritis and tubular epithelial inclusion bodies suggestive of HBV infection. Entecavir treatment slowed down the progression of his renal disease. Tubulointerstitial nephritis should be considered as a part of the differential diagnosis in patients with HBV infection. Early antiviral treatment may halt the progression of renal disease.

  11. Chronic exercise ameliorates the neuroinflammation in mice carrying NSE/htau23

    International Nuclear Information System (INIS)

    Leem, Yea-Hyun; Lee, Young-Ik; Son, Hee-Jeong; Lee, Sang-Ho

    2011-01-01

    Research highlights: → The progress of neurodegeration are directly linked to the neuroinflammatory response. → We investigate whether exercise improves the neuroinflammation using T g -NSE/htau23 mice. → This provides insights that exercise may beneficial effects on the neuroinflammatory disorders. -- Abstract: The objective of the present study was to investigate whether chronic endurance exercise attenuates the neuroinflammation in the brain of mice with NSE/htau23. In this study, the tau-transgenic (Tg) mouse, Tg-NSE/htau23, which over expresses human Tau23 in its brain, was subjected to chronic exercise for 3 months, from 16 months of age. The brains of Tg mice exhibited increased immunoreactivity and active morphological changes in GFAP (astrocyte marker) and MAC-1 (microglia marker) expression in an age-dependent manner. To identify the effects of chronic exercise on gliosis, the exercised Tg mice groups were treadmill run at a speed of 12 m/min (intermediate exercise group) or 19 m/min (high exercise group) for 1 h/day and 5 days/week during the 3 month period. The neuroinflammatory response characterized by activated astroglia and microglia was significantly repressed in the exercised Tg mice in an exercise intensity-dependent manner. In parallel, chronic exercise in Tg mice reduced the increased expression of TNF-α, IL-6, IL-1β, COX-2, and iNOS. Consistently with these changes, the levels of phospho-p38 and phospho-ERK were markedly downregulated in the brain of Tg mice after exercise. In addition, nuclear NF-κB activity was profoundly reduced after chronic exercise in an exercise intensity-dependent manner. These findings suggest that chronic endurance exercise may alleviate neuroinflammation in the Tau pathology of Alzheimer's disease.

  12. HBsAg-redirected T cells exhibit antiviral activity in HBV-infected human liver chimeric mice.

    Science.gov (United States)

    Kruse, Robert L; Shum, Thomas; Tashiro, Haruko; Barzi, Mercedes; Yi, Zhongzhen; Whitten-Bauer, Christina; Legras, Xavier; Bissig-Choisat, Beatrice; Garaigorta, Urtzi; Gottschalk, Stephen; Bissig, Karl-Dimiter

    2018-04-06

    Chronic hepatitis B virus (HBV) infection remains incurable. Although HBsAg-specific chimeric antigen receptor (HBsAg-CAR) T cells have been generated, they have not been tested in animal models with authentic HBV infection. We generated a novel CAR targeting HBsAg and evaluated its ability to recognize HBV+ cell lines and HBsAg particles in vitro. In vivo, we tested whether human HBsAg-CAR T cells would have efficacy against HBV-infected hepatocytes in human liver chimeric mice. HBsAg-CAR T cells recognized HBV-positive cell lines and HBsAg particles in vitro as judged by cytokine production. However, HBsAg-CAR T cells did not kill HBV-positive cell lines in cytotoxicity assays. Adoptive transfer of HBsAg-CAR T cells into HBV-infected humanized mice resulted in accumulation within the liver and a significant decrease in plasma HBsAg and HBV-DNA levels compared with control mice. Notably, the fraction of HBV core-positive hepatocytes among total human hepatocytes was greatly reduced after HBsAg-CAR T cell treatment, pointing to noncytopathic viral clearance. In agreement, changes in surrogate human plasma albumin levels were not significantly different between treatment and control groups. HBsAg-CAR T cells have anti-HBV activity in an authentic preclinical HBV infection model. Our results warrant further preclinical exploration of HBsAg-CAR T cells as immunotherapy for HBV. Copyright © 2018 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  13. Reduced spatial learning in mice infected with the nematode, Heligmosomoides polygyrus.

    Science.gov (United States)

    Kavaliers, M; Colwell, D D

    1995-06-01

    Parasite modification of host behaviour influences a number of critical responses, but little is known about the effects on host spatial abilities. This study examined the effects of infection with the intestinal trichostrongylid nematode, Heligmosomoides polygyrus, on spatial water maze learning by male laboratory mice, Mus musculus. In this task individual mice had to learn the spatial location of a submerged hidden platform using extramaze visual cues. Determinations of spatial performance were made on day 19 post-infection with mice that had been administered either 50 or 200 infective larvae of H. polygyrus. The infected mice displayed over 1 day of testing (6 blocks of 4 trials) significantly poorer acquisition and retention of the water maze task than either sham-infected or control mice, with mice that had received 200 infective larvae displaying significantly poorer spatial performance than individuals receiving 50 larvae. The decrease in spatial learning occurred in the absence of either any symptoms of illness and malaise, or any evident motor, visual and motivational impairments. It is suggested that in this single host system the parasitic infection-induced decrease in spatial learning arises as a side-effect of the host's immunological and neuromodulatory responses and represents a fitness cost of response to infection.

  14. Human glial chimeric mice reveal astrocytic dependence of JC virus infection

    DEFF Research Database (Denmark)

    Kondo, Yoichi; Windrem, Martha S; Zou, Lisa

    2014-01-01

    with humanized white matter by engrafting human glial progenitor cells (GPCs) into neonatal immunodeficient and myelin-deficient mice. Intracerebral delivery of JCV resulted in infection and subsequent demyelination of these chimeric mice. Human GPCs and astrocytes were infected more readily than...... that was chimeric for human astrocytes and GPCs. JCV effectively propagated in these mice, which indicates that astroglial infection is sufficient for JCV spread. Sequencing revealed progressive mutation of the JCV capsid protein VP1 after infection, suggesting that PML may evolve with active infection...

  15. Augmented effect of early antibiotic treatment in mice with experimental lung infections due to sequentially adapted mucoid strains of Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    van Gennip, M; Moser, Claus; Christensen, Louise D

    2009-01-01

    : A significant reduction in the number of bacteria was observed when initiating treatment 1 h post-infection compared with initiating treatment after 24 h, although the latest isolate avoided complete clearance. Early antibiotic treatment directed at the mucoid phenotype in mice also reduced the inflammation and......Background: Effects of treatment with tobramycin initiated 1 or 24 h post-infection were investigated in a new version of a pulmonary infection model in mice. The model reflects the differentiated behaviour of Pseudomonas aeruginosa mucoid strains isolated from the lungs of one chronically infected......, histopathology, and measurement of granulocyte colony-stimulating factor (G-CSF) and macrophage inflammatory protein 2 (MIP-2). Results: There was a significant reduction of bacteria when comparing treatment initiated 1 h post-infection with treatment initiated after 24 h for isolates 1997 and 2003. Treatment...

  16. TAM Receptors Are Not Required for Zika Virus Infection in Mice

    Directory of Open Access Journals (Sweden)

    Andrew K. Hastings

    2017-04-01

    Full Text Available Summary: Tyro3, Axl, and Mertk (TAM receptors are candidate entry receptors for infection with the Zika virus (ZIKV, an emerging flavivirus of global public health concern. To investigate the requirement of TAM receptors for ZIKV infection, we used several routes of viral inoculation and compared viral replication in wild-type versus Axl−/−, Mertk−/−, Axl−/−Mertk−/−, and Axl−/−Tyro3−/− mice in various organs. Pregnant and non-pregnant mice treated with interferon-α-receptor (IFNAR-blocking (MAR1-5A3 antibody and infected subcutaneously with ZIKV showed no reliance on TAMs for infection. In the absence of IFNAR-blocking antibody, adult female mice challenged intravaginally with ZIKV showed no difference in mucosal viral titers. Similarly, in young mice that were infected with ZIKV intracranially or intraperitoneally, ZIKV replication occurred in the absence of TAM receptors, and no differences in cell tropism were observed. These findings indicate that, in mice, TAM receptors are not required for ZIKV entry and infection. : TAM receptors have been implicated as entry receptors for the Zika virus. In this study, Hastings et al. used genetic knockout mouse models to demonstrate that they are not necessary for the infection of mice via multiple routes of viral challenge. These results suggest the existence of redundant entry receptors for ZIKV in mice. Keywords: viral entry, flavivirus, neurotropic virus, CNS, pregnancy, congenital infection

  17. Bioluminescence imaging of Chlamydia muridarum ascending infection in mice.

    Directory of Open Access Journals (Sweden)

    Jessica Campbell

    Full Text Available Chlamydial pathogenicity in the upper genital tract relies on chlamydial ascending from the lower genital tract. To monitor chlamydial ascension, we engineered a luciferase-expressing C. muridarum. In cells infected with the luciferase-expressing C. muridarum, luciferase gene expression and enzymatic activity (measured as bioluminescence intensity correlated well along the infection course, suggesting that bioluminescence can be used for monitoring chlamydial replication. Following an intravaginal inoculation with the luciferase-expressing C. muridarum, 8 of 10 mice displayed bioluminescence signal in the lower with 4 also in the upper genital tracts on day 3 after infection. By day 7, all 10 mice developed bioluminescence signal in the upper genital tracts. The bioluminescence signal was maintained in the upper genital tract in 6 and 2 mice by days 14 and 21, respectively. The bioluminescence signal was no longer detectable in any of the mice by day 28. The whole body imaging approach also revealed an unexpected airway infection following the intravaginal inoculation. Although the concomitant airway infection was transient and did not significantly alter the genital tract infection time courses, caution should be taken during data interpretation. The above observations have demonstrated that C. muridarum can not only achieve rapid ascending infection in the genital tract but also cause airway infection following a genital tract inoculation. These findings have laid a foundation for further optimizing the C. muridarum intravaginal infection murine model for understanding chlamydial pathogenic mechanisms.

  18. Biochemical changes after subchronic and chronic interaction of Schistosoma mansoni infection in Swiss albino mice with two specific compounds.

    Science.gov (United States)

    Hanna, Laila S; Medhat, Amina M; Abdel-Menem, Hanan A

    2003-04-01

    In Egypt, infection with Schistosoma mansoni (S.m.) and residues of pesticides have been considered as major environmental pollutants that adversely affect health. Effects of diazinon (DZN) and/or praziquantel (PZQ) on the levels of plasma triiodothyronine (T3), thyroxine (T4), activities of brain acetylcholinesterase (AchE) and liver alanine aminotransferase (ALT) in addition to blood reduced glutathione (GSH) in healthy and S.m. infected mice were investigated after 9 and 17 weeks of either infection or intoxication with DZN. Triiodothyronine showed significant differences among the different treatments. The group of mice treated with PZQ showed the highest levels of T3 at both time intervals. Thyroxine level showed significant differences between the two time intervals. The lowest levels of T4 were observed in the infected-PZQ group at week 17. The maximum inhibition of brain AchE activity was noticed in DZN-PZQ treated group after 9 and 17 weeks. The different treatments significantly reduced the activities of liver ALT. The highest decrease was recorded in the infected-DZN-PZQ group at week 9. All treatments significantly lowered the levels of blood GSH after 9 weeks.

  19. Antibody-independent mechanisms regulate the establishment of chronic Plasmodium infection

    Science.gov (United States)

    Lin, Jingwen; Cunningham, Deirdre; Tumwine, Irene; Kushinga, Garikai; McLaughlin, Sarah; Spence, Philip; Böhme, Ulrike; Sanders, Mandy; Conteh, Solomon; Bushell, Ellen; Metcalf, Tom; Billker, Oliver; Duffy, Patrick E.; Newbold, Chris; Berriman, Matthew; Langhorne, Jean

    2017-01-01

    Malaria is caused by parasites of the genus Plasmodium. All human-infecting Plasmodium species can establish long-lasting chronic infections1–5, creating an infectious reservoir to sustain transmission1,6. It is widely accepted that maintenance of chronic infection involves evasion of adaptive immunity by antigenic variation7. However, genes involved in this process have been identified in only two of five human-infecting species: P. falciparum and P. knowlesi. Furthermore, little is understood about the early events in establishment of chronic infection in these species. Using a rodent model we demonstrate that only a minority of parasites from among the infecting population, expressing one of several clusters of virulence-associated pir genes, establishes a chronic infection. This process occurs in different species of parasite and in different hosts. Establishment of chronicity is independent of adaptive immunity and therefore different from the mechanism proposed for maintainance of chronic P. falciparum infections7–9. Furthermore, we show that the proportions of parasites expressing different types of pir genes regulate the time taken to establish a chronic infection. Since pir genes are common to most, if not all, species of Plasmodium10, this process may be a common way of regulating the establishment of chronic infections. PMID:28165471

  20. Metabolic and adaptive immune responses induced in mice infected ...

    African Journals Online (AJOL)

    This study investigated metabolic and immuno-inflammatory responses of mice infected with tissue-dwelling larvae of Trichinella zimbabwensis and explored the relationship between infection, metabolic parameters and Th1/Th17 immune responses. Sixty (60) female BALB/c mice aged between 6 to 8 weeks old were ...

  1. Chronic social stress leads to altered sleep homeostasis in mice.

    Science.gov (United States)

    Olini, Nadja; Rothfuchs, Iru; Azzinnari, Damiano; Pryce, Christopher R; Kurth, Salome; Huber, Reto

    2017-06-01

    Disturbed sleep and altered sleep homeostasis are core features of many psychiatric disorders such as depression. Chronic uncontrollable stress is considered an important factor in the development of depression, but little is known on how chronic stress affects sleep regulation and sleep homeostasis. We therefore examined the effects of chronic social stress (CSS) on sleep regulation in mice. Adult male C57BL/6 mice were implanted for electrocortical recordings (ECoG) and underwent either a 10-day CSS protocol or control handling (CON). Subsequently, ECoG was assessed across a 24-h post-stress baseline, followed by a 4-h sleep deprivation, and then a 20-h recovery period. After sleep deprivation, CSS mice showed a blunted increase in sleep pressure compared to CON mice, as measured using slow wave activity (SWA, electroencephalographic power between 1-4Hz) during non-rapid eye movement (NREM) sleep. Vigilance states did not differ between CSS and CON mice during post-stress baseline, sleep deprivation or recovery, with the exception of CSS mice exhibiting increased REM sleep during recovery sleep. Behavior during sleep deprivation was not affected by CSS. Our data provide evidence that CSS alters the homeostatic regulation of sleep SWA in mice. In contrast to acute social stress, which results in a faster SWA build-up, CSS decelerates the homeostatic build up. These findings are discussed in relation to the causal contribution of stress-induced sleep disturbance to depression. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Pharmacological manipulation of the chronic granulomatous reactions in the livers of mice infected with schistosomiasis.

    Science.gov (United States)

    Rainsford, K D

    1985-01-01

    The severe granulomatous reactions in the liver which occur following infestation by adult Schistosoma mansonii are largely initiated by invading eosinophils and monocytes. The present studies were designed to investigate the possibility that (a) anti-inflammatory drugs could be employed beneficially to attenuate the liver granulomatous reactions in schistosomiasis, and (b) that part of the therapeutic effects of anti-schistosomal (AS) drugs might be due to possible influences on arachidonate metabolism. Therefore the effects were determined of (a) AS as compared with NSAI drugs on eicosanoid metabolism in isolated human peripheral leucocyte populations, and (b) electron-microscopic changes in the livers of mice infected with Schistosoma mansoni in response to AS and/or NSAI drugs. Of the AS drugs only praziquantel (10-100 microM) inhibited 5-HETE production by the 5-lipoxygenase pathway. No effects were observed of this or the other AS drugs on prostaglandin production. In S. mansoni infected mice, praziquantel (250 mg/kg/d), given orally with indomethacin (5 mg/kg/d) for 5 days did not improve the inflammatory reactions around worms or eggs of schistosomes. Furthermore, both indomethacin (5 mg/kg/d) alone and benoxaprofen (20 mg/kg/d for 5 days) elicited liver changes suggestive of specific liver damage by these drugs. These results suggest that liver pathology may be enhanced by NSAI drugs perhaps as a consequence of the liver metabolism of these drugs being compromised. Their use to modify inflammatory reactions at the peak of liver schistosome infections may thus be contraindicated.

  3. Innate and adaptive immune response to chronic pulmonary infection of hyphae of Aspergillus fumigatus in a new murine model.

    Science.gov (United States)

    Wang, Fengyuan; Zhang, Caiyun; Jiang, Yuan; Kou, Caixia; Kong, Qingtao; Long, Nanbiao; Lu, Ling; Sang, Hong

    2017-10-01

    The pathogenesis of chronic pulmonary aspergillosis (CPA) has seldom been studied due partly to a lack of animal models. Since hypha is the main morphology colonizing the airway in CPA, it's critical to study the immune reaction to chronic pulmonary infection of hyphae of Aspergillus fumigatus, which also has seldom been studied in vivo before. We established a novel murine model of chronic pulmonary infection of hyphae by challenging immunocompetent mice with tightly-structured hyphae balls intratracheally, and described the ensuing immunoreaction to hyphae and conidia, and the pathogenesis of CPA. Our experiment proved that the hyphae balls could induce a chronic pulmonary infection for 28 days with a considerable recrudescence at day 28 post-infection. Lungs infected with hyphae balls were remarkable for the many neutrophils and macrophages that flooded into airway lumens, with peribronchiolar infiltration of leukocytes. There was a transient increase of Th2 cells and Th17 cells at day 7 post-infection in the lung tissue. In contrast, lungs infected with conidia showed no peribronchiolar infiltration of leukocytes, but an influx of a great number of macrophages, and a much less number of neutrophils in the lumen. Besides, conidia activated the co-response of Th1, Th2 and Th17 cells with an increase of Treg cells in the lung tissue (quite different from most previous studies). We established a new murine model of chronic infection of hyphae to mimic the formation of CPA, and provide a new marker for different immune responses to hyphae and conidia.

  4. IFNγ and perforin cooperate to control infection and prevent fatal pathology during persistent gammaherpesvirus infection in mice

    DEFF Research Database (Denmark)

    Bartholdy, Christina; Høgh-Petersen, Mette; Storm, Pernille

    2014-01-01

    herpes virus infection, we infected IFNγ/perforin double deficient C57BL/6 mice and followed the outcome of infection. While absence of perforin prevented the splenic atrophy in IFNγ deficient mice, fibrosis did not disappear. Moreover, double deficient mice developed extreme splenomegaly, were unable...... in double deficient mice, other aspects are exaggerated, and the normal architecture of the spleen is completely destroyed. Thus, IFNγ and perforin work in concert to minimize pathology and control the viral load. In the absence of both effector molecules, the balancing race between the virus and the host...

  5. Chronic mucus hypersecretion in COPD and death from pulmonary infection

    DEFF Research Database (Denmark)

    Prescott, E; Lange, P; Vestbo, J

    1995-01-01

    The association of chronic mucus hypersecretion and mortality is a matter of debate. We wished to determine whether the relationship between chronic mucus hypersecretion and chronic obstructive pulmonary disease (COPD)-related mortality could be explained by proneness to pulmonary infection. We...... with pulmonary infection implicated (relative risk (RR) 3.5) but not of death without pulmonary infection (RR 0.9). We consider that subjects with COPD and chronic mucus hypersecretion are more likely to die from pulmonary infections than subjects without chronic mucus hypersecretion. This may explain the excess...... radiography, death was classified as either due to pulmonary infection (n = 38), other causes (n = 51), or unclassifiable (n = 12). Of subjects reporting chronic mucus hypersecretion at the initial examination, pulmonary infection was implicated in 54% of deaths, whereas this only occurred in 28% of subjects...

  6. TAM Receptors Are Not Required for Zika Virus Infection in Mice.

    Science.gov (United States)

    Hastings, Andrew K; Yockey, Laura J; Jagger, Brett W; Hwang, Jesse; Uraki, Ryuta; Gaitsch, Hallie F; Parnell, Lindsay A; Cao, Bin; Mysorekar, Indira U; Rothlin, Carla V; Fikrig, Erol; Diamond, Michael S; Iwasaki, Akiko

    2017-04-18

    Tyro3, Axl, and Mertk (TAM) receptors are candidate entry receptors for infection with the Zika virus (ZIKV), an emerging flavivirus of global public health concern. To investigate the requirement of TAM receptors for ZIKV infection, we used several routes of viral inoculation and compared viral replication in wild-type versus Axl -/- , Mertk -/- , Axl -/- Mertk -/- , and Axl -/- Tyro3 -/- mice in various organs. Pregnant and non-pregnant mice treated with interferon-α-receptor (IFNAR)-blocking (MAR1-5A3) antibody and infected subcutaneously with ZIKV showed no reliance on TAMs for infection. In the absence of IFNAR-blocking antibody, adult female mice challenged intravaginally with ZIKV showed no difference in mucosal viral titers. Similarly, in young mice that were infected with ZIKV intracranially or intraperitoneally, ZIKV replication occurred in the absence of TAM receptors, and no differences in cell tropism were observed. These findings indicate that, in mice, TAM receptors are not required for ZIKV entry and infection. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  7. Detection of toxoplasma gondii antigens in sera from experimentally infected mice

    International Nuclear Information System (INIS)

    Shojaee, S.; Keshavarz, H.; Rezaian, M.; Mohebali, M.

    2007-01-01

    Detection of Toxoplasma antigen in serum of mice by Immunoblotting. strain. IgG isolated from rabbits that were immunized with T. gondii Immunoblotting was performed to detect T. gondii antigens in sera of mice. Serum samples from mice experimentally infected with T. gondii RH strain. The value of Immunoblotting in diagnosis of toxoplasmosis in acute stage of infection. The antigen bands detected in serum sample of mice were experimentally infected with T. gondii tachyzoite in immunoblotting. Six bands demonstrated on seventh post infection day six bands were identified. Similarly on sixth day four bands, on day five three bands and on fourth post infection day two bands were identified. No band was detected in control group sera. Immunoblotting is a sensitive method for diagnosis of acute stage of toxoplasmosis. (author)

  8. Coping with parvovirus infections in mice: health surveillance and control.

    Science.gov (United States)

    Janus, Lydia M; Bleich, Andre

    2012-01-01

    Parvoviruses of mice, minute virus of mice (MVM) and mouse parvovirus (MPV), are challenging pathogens to eradicate from laboratory animal facilities. Due to the impediment on rodent-based research, recent studies have focused on the assessment of re-derivation techniques and parvoviral potential to induce persistent infections. Summarizing recent data, this review gives an overview on studies associated with parvoviral impact on research, diagnostic methods, parvoviral persistence and re-derivation techniques, demonstrating the complex nature of parvovirus infection in mice and unfolding the challenge of controlling parvovirus infections in laboratory animal facilities.

  9. Effect of Delta-9-tetrahydrocannabinol on mouse resistance to systemic Candida albicans infection.

    Directory of Open Access Journals (Sweden)

    Gideon W Blumstein

    Full Text Available Delta-9-tetrahydrocannabinol (Δ9-THC, the psychoactive component of marijuana, is known to suppress the immune responses to bacterial, viral and protozoan infections, but its effects on fungal infections have not been studied. Therefore, we investigated the effects of chronic Δ9-THC treatment on mouse resistance to systemic Candida albicans (C. albicans infection. To determine the outcome of chronic Δ9-THC treatment on primary, acute systemic candidiasis, c57BL/6 mice were given vehicle or Δ9-THC (16 mg/kg in vehicle on days 1-4, 8-11 and 15-18. On day 19, mice were infected with 5×10(5 C. albicans. We also determined the effect of chronic Δ9-THC (4-64 mg/kg treatment on mice infected with a non-lethal dose of 7.5×10(4 C. albicans on day 2, followed by a higher challenge with 5×10(5 C. albicans on day 19. Mouse resistance to the infection was assessed by survival and tissue fungal load. Serum cytokine levels were determine to evaluate the immune responses. In the acute infection, chronic Δ9-THC treatment had no effect on mouse survival or tissue fungal load when compared to vehicle treated mice. However, Δ9-THC significantly suppressed IL-12p70 and IL-12p40 as well as marginally suppressed IL-17 versus vehicle treated mice. In comparison, when mice were given a secondary yeast infection, Δ9-THC significantly decreased survival, increased tissue fungal burden and suppressed serum IFN-γ and IL-12p40 levels compared to vehicle treated mice. The data showed that chronic Δ9-THC treatment decreased the efficacy of the memory immune response to candida infection, which correlated with a decrease in IFN-γ that was only observed after the secondary candida challenge.

  10. Administration of kefir-fermented milk protects mice against Giardia intestinalis infection.

    Science.gov (United States)

    Franco, Mariana Correa; Golowczyc, Marina A; De Antoni, Graciela L; Pérez, Pablo F; Humen, Martín; Serradell, María de los Angeles

    2013-12-01

    Giardiasis, caused by the protozoan Giardia intestinalis, is one of the most common intestinal diseases worldwide and constitutes an important problem for the public health systems of various countries. Kefir is a probiotic drink obtained by fermenting milk with 'kefir grains', which consist mainly of bacteria and yeasts that coexist in a complex symbiotic association. In this work, we studied the ability of kefir to protect mice from G. intestinalis infection, and characterized the host immune response to this probiotic in the context of the intestinal infection. Six- to 8-week-old C75BL/6 mice were separated into four groups: controls, kefir mice (receiving 1 : 100 dilution of kefir in drinking water for 14 days), Giardia mice (infected orally with 4×10(7) trophozoites of G. intestinalis at day 7) and Giardia-kefir mice (kefir-treated G. intestinalis-infected mice), and killed at 2 or 7 days post-infection. Kefir administration was able to significantly reduce the intensity of Giardia infection at 7 days post-infection. An increase in the percentage of CD4(+) T cells at 2 days post-infection was observed in the Peyer's patches (PP) of mice belonging to the Giardia group compared with the control and kefir groups, while the percentage of CD4(+) T cells in PP in the Giardia-kefir group was similar to that of controls. At 2 days post-infection, a reduction in the percentage of B220-positive major histocompatibility complex class II medium cells in PP was observed in infected mice compared with the other groups. At 7 days post-infection, Giardia-infected mice showed a reduction in RcFcε-positive cells compared with the control group, suggesting a downregulation of the inflammatory response. However, the percentages of RcFcε-positive cells did not differ from controls in the kefir and Giardia-kefir groups. An increase in IgA-positive cells was observed in the lamina propria of the kefir group compared with controls at 2 days post-infection. Interestingly, the

  11. Biofilms in chronic infections - a matter of opportunity - monospecies biofilms in multispecies infections

    DEFF Research Database (Denmark)

    Burmølle, Mette; Thomsen, Trine Rolighed; Fazli, Mustafa

    2010-01-01

    It has become evident that aggregation or biofilm formation is an important survival mechanism for bacteria in almost any environment. In this review, we summarize recent visualizations of bacterial aggregates in several chronic infections (chronic otitis media, cystic fibrosis, infection due...... to permanent tissue fillers and chronic wounds) both as to distribution (such as where in the wound bed) and organization (monospecies or multispecies microcolonies). We correlate these biofilm observations to observations of commensal biofilms (dental and intestine) and biofilms in natural ecosystems (soil......). The observations of the chronic biofilm infections point toward a trend of low bacterial diversity and sovereign monospecies biofilm aggregates even though the infection in which they reside are multispecies. In contrast to this, commensal and natural biofilm aggregates contain multiple species that are believed...

  12. Nocardia brasiliensis induces an immunosuppressive microenvironment that favors chronic infection in BALB/c mice.

    Science.gov (United States)

    Rosas-Taraco, Adrian G; Perez-Liñan, Amira R; Bocanegra-Ibarias, Paola; Perez-Rivera, Luz I; Salinas-Carmona, Mario C

    2012-07-01

    Nocardia brasiliensis is an intracellular microorganism and the most common etiologic agent of actinomycetoma in the Americas. Several intracellular pathogens induce an immunosuppressive microenvironment through increases in CD4+ Foxp3+ regulatory T cells (Treg), thus downregulating other T-cell subpopulations and assuring survival in the host. In this study, we determined whether N. brasiliensis modulates T-lymphocyte responses and their related cytokine profiles in a murine experimental model. We also examined the relationship between N. brasiliensis immunomodulation and pathogenesis and bacterial survival. In early infection, Th17/Tc17 cells were increased at day 3 (P 1 log) was also observed (P brasiliensis modulates the immune system to induce an immunosuppressive microenvironment that benefits its survival during the chronic stage of infection.

  13. EXPERIMENTAL-INFECTION IN MICE WITH BACILLUS-LICHENIFORMIS

    DEFF Research Database (Denmark)

    Agerholm, J.S.; Jensen, H.E.; Jensen, N.E.

    1995-01-01

    The pathogenicity of Bacillus licheniformis was assessed in normal and immunodepressed BALB/c mice. The animals were challenged intravenously with 4 x 10(7) colony forming units of B, licheniformis (ATCC 14580) and both normal and immunodepressed mice were susceptible. However, the infection...... was more severe in the immunosuppressed animals. In normal mice, lesions were restricted to the liver and kidneys, while lesions also occurred in other organs of immunodepressed mice. By crossed immunoelectrophoresis it was shown that antigens of B. licheniformis are potent immunogens, and the bacteria...

  14. Antibody hyporesponsiveness in resistant BALB/cJ mice intracorneally infected with Pseudomonas aeruginosa.

    Science.gov (United States)

    Berk, R S; Preston, M; Montgomery, I N; Hazlett, L D; Tse, H Y

    Six- to eight-week-old BALB/cJ (and BALB/cPi) mice were found able to restore corneal clarity within 3 to 4 weeks after intracorneal infection with Pseudomonas aeruginosa strain 19660. However, enzyme-linked immunosorbent assay (ELISA) for serum immunoglobulins directed specifically against P. aeruginosa indicated that the mice were initially non- or hypo-responsive for IgG and IgA over the 4-week holding period. Low IgM titers could be detected 1 week after infection, but tended to decrease with time. When the mice were re-infected by using the contralateral control eye, then the serum IgG levels began to gradually increase as the time interval following the secondary infection increased from 1 to 3 weeks. Re-infected mice did not show a significantly increased rate of corneal clarity restoration with time, when compared to the corneas of mice receiving only a primary infection despite the presence of serum antibodies specific to P. aeruginosa. When congenic mice of the BALB/c background carrying the DBA/2N Idh/Pep-3 locus found on chromosome 1 were intracorneally infected, they tended to restore corneal clarity at approximately the same rate as the BALB/cJ mice. However, the congenic mice mounted a faster and substantially greater magnitude of serum IgM and IgG response during the primary infection than BALB/cJ mice receiving either a primary and/or secondary infection. IgG subclass studies with the congenic mice indicated that serum IgG1, and IgG2a to a lesser extent, were the primary immunoglobulins produced and no major shift in subclass was noted with time during the primary infection.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Chronic Toxoplasma gondii in Nurr1-null heterozygous mice exacerbates elevated open field activity.

    Science.gov (United States)

    Eells, Jeffrey B; Varela-Stokes, Andrea; Guo-Ross, Shirley X; Kummari, Evangel; Smith, Holly M; Cox, Erin; Lindsay, David S

    2015-01-01

    Latent infection with Toxoplasma gondii is common in humans (approximately 30% of the global population) and is a significant risk factor for schizophrenia. Since prevalence of T. gondii infection is far greater than prevalence of schizophrenia (0.5-1%), genetic risk factors are likely also necessary to contribute to schizophrenia. To test this concept in an animal model, Nurr1-null heterozygous (+/-) mice and wild-type (+/+) mice were evaluate using an emergence test, activity in an open field and with a novel object, response to bobcat urine and prepulse inhibition of the acoustic startle response (PPI) prior to and 6 weeks after infection with T. gondii. In the emergence test, T. gondii infection significantly decreased the amount of time spent in the cylinder. Toxoplasma gondii infection significantly elevated open field activity in both +/+ and +/- mice but this increase was significantly exacerbated in +/- mice. T. gondii infection reduced PPI in male +/- mice but this was not statistically significant. Aversion to bobcat urine was abolished by T. gondii infection in +/+ mice. In female +/- mice, aversion to bobcat urine remained after T. gondii infection while the male +/- mice showed no aversion to bobcat urine. Antibody titers of infected mice were a critical variable associated with changes in open field activity, such that an inverted U shaped relationship existed between antibody titers and the percent change in open field activity with a significant increase in activity at low and medium antibody titers but no effect at high antibody titers. These data demonstrate that the Nurr1 +/- genotype predisposes mice to T. gondii-induced alterations in behaviors that involve dopamine neurotransmission and are associated with symptoms of schizophrenia. We propose that these alterations in murine behavior were due to further exacerbation of the altered dopamine neurotransmission in Nurr1 +/- mice.

  16. Chronic Toxoplasma gondii in Nurr1-null heterozygous mice exacerbates elevated open field activity.

    Directory of Open Access Journals (Sweden)

    Jeffrey B Eells

    Full Text Available Latent infection with Toxoplasma gondii is common in humans (approximately 30% of the global population and is a significant risk factor for schizophrenia. Since prevalence of T. gondii infection is far greater than prevalence of schizophrenia (0.5-1%, genetic risk factors are likely also necessary to contribute to schizophrenia. To test this concept in an animal model, Nurr1-null heterozygous (+/- mice and wild-type (+/+ mice were evaluate using an emergence test, activity in an open field and with a novel object, response to bobcat urine and prepulse inhibition of the acoustic startle response (PPI prior to and 6 weeks after infection with T. gondii. In the emergence test, T. gondii infection significantly decreased the amount of time spent in the cylinder. Toxoplasma gondii infection significantly elevated open field activity in both +/+ and +/- mice but this increase was significantly exacerbated in +/- mice. T. gondii infection reduced PPI in male +/- mice but this was not statistically significant. Aversion to bobcat urine was abolished by T. gondii infection in +/+ mice. In female +/- mice, aversion to bobcat urine remained after T. gondii infection while the male +/- mice showed no aversion to bobcat urine. Antibody titers of infected mice were a critical variable associated with changes in open field activity, such that an inverted U shaped relationship existed between antibody titers and the percent change in open field activity with a significant increase in activity at low and medium antibody titers but no effect at high antibody titers. These data demonstrate that the Nurr1 +/- genotype predisposes mice to T. gondii-induced alterations in behaviors that involve dopamine neurotransmission and are associated with symptoms of schizophrenia. We propose that these alterations in murine behavior were due to further exacerbation of the altered dopamine neurotransmission in Nurr1 +/- mice.

  17. Complement C3 deficiency attenuates chronic hypoxia-induced pulmonary hypertension in mice.

    Directory of Open Access Journals (Sweden)

    Eileen M Bauer

    Full Text Available Evidence suggests a role of both innate and adaptive immunity in the development of pulmonary arterial hypertension. The complement system is a key sentry of the innate immune system and bridges innate and adaptive immunity. To date there are no studies addressing a role for the complement system in pulmonary arterial hypertension.Immunofluorescent staining revealed significant C3d deposition in lung sections from IPAH patients and C57Bl6/J wild-type mice exposed to three weeks of chronic hypoxia to induce pulmonary hypertension. Right ventricular systolic pressure and right ventricular hypertrophy were increased in hypoxic vs. normoxic wild-type mice, which were attenuated in C3-/- hypoxic mice. Likewise, pulmonary vascular remodeling was attenuated in the C3-/- mice compared to wild-type mice as determined by the number of muscularized peripheral arterioles and morphometric analysis of vessel wall thickness. The loss of C3 attenuated the increase in interleukin-6 and intracellular adhesion molecule-1 expression in response to chronic hypoxia, but not endothelin-1 levels. In wild-type mice, but not C3-/- mice, chronic hypoxia led to platelet activation as assessed by bleeding time, and flow cytometry of platelets to determine cell surface P-selectin expression. In addition, tissue factor expression and fibrin deposition were increased in the lungs of WT mice in response to chronic hypoxia. These pro-thrombotic effects of hypoxia were abrogated in C3-/- mice.Herein, we provide compelling genetic evidence that the complement system plays a pathophysiologic role in the development of PAH in mice, promoting pulmonary vascular remodeling and a pro-thrombotic phenotype. In addition we demonstrate C3d deposition in IPAH patients suggesting that complement activation plays a role in the development of PAH in humans.

  18. Perfluorocarbon emulsion therapy attenuates pneumococcal infection in sickle cell mice.

    Science.gov (United States)

    Helmi, Nawal; Andrew, Peter W; Pandya, Hitesh C

    2015-05-15

    Impaired immunity and tissue hypoxia-ischemia are strongly linked with Streptococcus pneumoniae pathogenesis in patients with sickle cell anemia. Perfluorocarbon emulsions (PFCEs) have high O2-dissolving capacity and can alleviate tissue hypoxia. Here, we evaluate the effects of intravenous PFCE therapy in transgenic sickle cell (HbSS) mice infected with S. pneumoniae. HbSS and C57BL/6 (control) mice intravenously infected with S. pneumoniae were treated intravenously with PFCE or phosphate-buffered saline (PBS) and then managed in either air/O2 (FiO2 proportion, 50%; hereafter referred to as the PFCE-O2 and PBS-O2 groups) or air only (hereafter, the PFCE-air and PBS-air groups) gas mixtures. Lungs were processed for leukocyte and bacterial counts and cytokine measurements. HbSS mice developed severe pneumococcal infection significantly faster than C57BL/6 mice (Kaplan-Maier analysis, P < .05). PFCE-O2-treated HbSS mice had significantly better survival at 72 hours than HBSS mice treated with PFCE-air, PBS-O2, or PBS-air (P < .05). PFCE-O2-treated HbSS mice also had significantly lower pulmonary leukocyte counts, lower interleukin 1β and interferon γ levels, and higher interleukin 10 levels than PFCE-air-treated HbSS mice. Clearance of S. pneumoniae from lungs of HbSS mice or C57BL/6 mice was not altered by PFCE treatment. Improved survival of PFCE-O₂-treated HbSS mice infected with S. pneumoniae is associated with altered pulmonary inflammation but not enhanced bacterial clearance. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. Extraneural manifestations of prion infection in GPI-anchorless transgenic mice

    International Nuclear Information System (INIS)

    Lee, Andrew M.; Paulsson, Johan F.; Cruite, Justin; Andaya, Abegail A.; Trifilo, Matthew J.; Oldstone, Michael B.A.

    2011-01-01

    Earlier studies indicated that transgenic (tg) mice engineered to express prion protein (PrP) lacking the glycophosphatidylinositol (GPI -/- ) membrane anchor formed abnormal proteinase-resistant prion (PrPsc) amyloid deposits in their brains and hearts when infected with the RML strain of murine scrapie. In contrast, RML scrapie infection of normal mice with a GPI-anchored PrP did not deposit amyloid with PrPsc in the brain or the heart. Here we report that scrapie-infected GPI -/- PrP tg mice also deposit PrP and transmissible infectious material in the gut, kidneys, and islets of Langerhans. Similar to previously reported amyloid deposits in the brain and heart, amyloid deposits were found in the gut; however, no amyloid deposited in the islets. By high-resolution electron microscopy, we show PrP is located primarily in α cells and also β cells. Islets contain abundant insulin and there is no abnormality in glucose metabolism in infected GPI -/- PrP tg mice.

  20. Effects of testosterone on blood leukocytes in plasmodium berghei-infected mice.

    Science.gov (United States)

    Kamis, A B; Ibrahim, J B

    1989-01-01

    Gonadectomized male mice aged 5 weeks were given 5 mg testosterone propionate daily for 14 days. The treatment significantly decreased the number of blood leukocytes. The number of all individual types of leukocytes except basophils in vehicle-treated gonadectomized mice was increased. Testosterone-treated mice consistently had a lower number of leukocytes after being infected with Plasmodium berghei than did vehicle-treated mice. The results suggest that testosterone suppresses the production of leukocytes and that testosterone-treated mice become more susceptible to parasite infection.

  1. Porphyromonas gingivalis infection induced reproductive abnormalities in mice

    Directory of Open Access Journals (Sweden)

    Ke-min WEI

    2016-09-01

    Full Text Available Objective  To establish a pregnant mouse model infected with Porphyromonas gingivalis (P.g, and investigate the relationship of P.g infection to prematurity and associated birth abnormalities. Methods  Fifty two female mice were randomly divided into P.g infection group (n=26 and control group (n=26. Mice in P.g infection group were anesthetized, the pulp cavity of the first molar was opened and directly injected with W83 strain P.g, and the tooth was then filled. Six weeks after infection, the mice were mated with males and the formation of vagina plug was recorded as 0d. The P.g extracted from the granulation tissue in tooth root was cultivated. The pregnant days and the connatal body weight of infant mouse were recorded, the serum and placental tissue were collected to assess the systemic and local conditions during pregnancy. Results  After periodontal P.g infection, the TNF-α, IL-17, IL -6 and IL -1βlevels in peripheral blood sera increased significantly. The average gestation was shorter in P.g infection group (18.25d than in control group (20.45d, P<0.01, and the connatal body weight of infant mouse was also less in the former than in the latter (P<0.01. Immunohistochemistry and PCR revealed the existence of P.g in placenta tissue. P.g infection caused premature rupture of membranes, placental abruption, degeneration and necrosis of trophoblastic and endothelial cells; significantly increased the number of neutrophils and macrophages in placenta tissues, and increased the expression of local TNF-αand COX-2 inflammatory factors at the same time. In P.g infection group, the expressions of CD-31 in endothelial cells of placenta tissues and the apoptotic factor caspase-3 decreased, and the DNA oxidative damage index 8-OHdG increased. Conclusions  P.g infection in female mice may cause premature birth and lower connatal body weight of infant mouse, and increase the expression of serous and local inflammatory factors in the placenta

  2. Diagnosis and understanding of chronic biofilm infections

    DEFF Research Database (Denmark)

    Thomsen, Trine Rolighed

    2016-01-01

    Title: Diagnosis and understanding of chronic biofilm infections. Name: Trine Rolighed Thomsen Aalborg University and Danish Technological Institute, Denmark Recent evidence suggests that the microbial community, its spatial distribution and activity play an important role in the prolongation......, anaerobic or unculturable bacteria living in biofilms. Thus, diagnosis of chronic infections is challenged by lack of appropriate sampling strategies and by limitations in microbiological testing methods. The purpose of this study was to improve sampling and diagnosis of chronic infections, especially...... considering the biofilm issue. Systematic and optimized sampling of various specimen types was performed. Extended culture, optimized DNA extraction, quantitative PCR, cloning, next generation sequencing and PNA FISH were applied on different types of specimens for optimized diagnosis. For further...

  3. Helicobacter sp. MIT 01-6451 infection during fetal and neonatal life in laboratory mice.

    Science.gov (United States)

    Yamanaka, Hitoki; Nakanishi, Tai; Takagi, Toshikazu; Ohsawa, Makiko; Kubo, Noriaki; Yamamoto, Naoto; Takemoto, Takahira; Ohsawa, Kazutaka

    2015-01-01

    Helicobacter sp. MIT 01-6451 has been detected in SPF mice kept in Japan. To characterize strain MIT 01-6451, its infection route during fetal and neonatal life and effects on pregnancy were investigated using immunocompetent and immunodeficient mouse strains (BALB/c, C57BL/6, and SCID). MIT 01-6451 was detected in the uterus, vagina, and mammary glands of 50% of infected SCID mice, whereas these tissues were all negative in immunocompetent mice. No fetal infections with MIT 01-6451 were detected at 16-18 days after pregnancy in any mouse strain. In newborn mice, MIT 01-6451 was detected in intestinal tissue of C57BL/6 and SCID mice at 9-11 days after birth, but not in BALB/c mice. The IgA and IgG titers to MIT 01-6451 in sera of C57BL/6 female mice were significantly lower than those of BALB/c mice. Although no significant differences in the number of newborns per litter were observed between MIT 01-6451-infected and MIT 01-6451-free dams, the birth rate was lower in infected SCID mice than in control SCID mice. The present results indicated that MIT 01-6451 infects newborn mice after birth rather than by vertical transmission to the fetus via the placenta and that MIT 01-6451 infection shows opportunistically negative effects on the birth rate. In addition, the maternal immune response may affect infection of newborn mice with MIT 01-6451 through breast milk.

  4. Chronic psychosocial stress disturbs long-bone growth in adolescent mice

    Directory of Open Access Journals (Sweden)

    Sandra Foertsch

    2017-12-01

    Full Text Available Although a strong association between psychiatric and somatic disorders is generally accepted, little is known regarding the interrelationship between mental and skeletal health. Although depressive disorders have been shown to be strongly associated with osteoporosis and increased fracture risk, evidence from post-traumatic stress disorder (PTSD patients is less consistent. Therefore, the present study investigated the influence of chronic psychosocial stress on bone using a well-established murine model for PTSD. C57BL/6N mice (7 weeks old were subjected to chronic subordinate colony housing (CSC for 19 days, whereas control mice were singly housed. Anxiety-related behavior was assessed in the open-field/novel-object test, after which the mice were euthanized to assess endocrine and bone parameters. CSC mice exhibited increased anxiety-related behavior in the open-field/novel-object test, increased adrenal and decreased thymus weights, and unaffected plasma morning corticosterone. Microcomputed tomography and histomorphometrical analyses revealed significantly reduced tibia and femur lengths, increased growth-plate thickness and reduced mineral deposition at the growth plate, suggesting disturbed endochondral ossification during long-bone growth. This was associated with reduced Runx2 expression in hypertrophic chondrocytes in the growth plate. Trabecular thicknesses and bone mineral density were significantly increased in CSC compared to singly housed mice. Tyrosine hydroxylase expression was increased in bone marrow cells located at the growth plates of CSC mice, implying that local adrenergic signaling might be involved in the effects of CSC on the skeletal phenotype. In conclusion, chronic psychosocial stress negatively impacts endochondral ossification in the growth plate, affecting both longitudinal and appositional bone growth in adolescent mice.

  5. Primary peak and chronic malaria infection levels are correlated in experimentally infected great reed warblers.

    Science.gov (United States)

    Asghar, Muhammad; Westerdahl, Helena; Zehtindjiev, Pavel; Ilieva, Mihaela; Hasselquist, Dennis; Bensch, Staffan

    2012-09-01

    Malaria parasites often manage to maintain an infection for several months or years in their vertebrate hosts. In humans, rodents and birds, most of the fitness costs associated with malaria infections are in the short initial primary (high parasitaemia) phase of the infection, whereas the chronic phase (low parasitaemia) is more benign to the host. In wild birds, malaria parasites have mainly been studied during the chronic phase of the infection. This is because the initial primary phase of infection is short in duration and infected birds with severe disease symptoms tend to hide in sheltered places and are thus rarely caught and sampled. We therefore wanted to investigate the relationship between the parasitaemia during the primary and chronic phases of the infection using an experimental infection approach. We found a significant positive correlation between parasitaemia in the primary peak and the subsequent chronic phase of infection when we experimentally infected great reed warblers (Acrocephalus arundinaceus) with Plasmodium ashfordi. The reason for this association remains to be understood, but might arise from individual variation in exoerythrocytic parasite reservoirs in hosts, parasite antigenic diversity and/or host genetics. Our results suggest that the chronic phase parasitaemia can be used to qualitatively infer the parasitaemia of the preceding and more severe primary phase, which is a very important finding for studies of avian malaria in wild populations.

  6. Histopathological analysis of Salmonella chronic carriage in the mouse hepatopancreatobiliary system.

    Directory of Open Access Journals (Sweden)

    Geoffrey Gonzalez-Escobedo

    Full Text Available Salmonella Typhi asymptomatic chronic carriage represents a challenge for the diagnosis and prevention of typhoid fever in endemic areas. Such carriers are thought to be reservoirs for further spread of the disease. Gallbladder carriage has been demonstrated to be mediated by biofilm formation on gallstones and by intracellular persistence in the gallbladder epithelium of mice. In addition, both gallstones and chronic carriage have been associated with chronic inflammation and the development of gallbladder carcinoma. However, the pathogenic relationship between typhoid carriage and the development of pre-malignant and/or malignant lesions in the hepatopancreatobiliary system as well as the host-pathogen interactions occurring during chronic carriage remains unclear. In this study, we monitored the histopathological features of chronic carriage up to 1 year post-infection. Chronic cholecystitis and hepatitis ranging from mild to severe were present in infected mice regardless of the presence of gallstones. Biliary epithelial hyperplasia was observed more commonly in the gallbladder of mice with gallstones (uninfected or infected. However, pre-malignant lesions, atypical hyperplasia and metaplasia of the gallbladder and exocrine pancreas, respectively, were only associated with chronic Salmonella carriage. This study has implications regarding the role of Salmonella chronic infection and inflammation in the development of pre-malignant lesions in the epithelium of the gallbladder and pancreas that could lead to oncogenesis.

  7. Novel mouse model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis

    DEFF Research Database (Denmark)

    Hoffmann, Nadine; Rasmussen, Thomas Bovbjerg; Jensen, Peter Østrup

    2005-01-01

    (NH57388C) from the mucoid isolate (NH57388A) and a nonmucoid isolate (NH57388B) deficient in AHL were almost cleared from the lungs of the mice. This model, in which P. aeruginosa is protected against the defense system of the lung by alginate, is similar to the clinical situation. Therefore...... pulmonary mouse model without artificial embedding. The model is based on a stable mucoid CF sputum isolate (NH57388A) with hyperproduction of alginate due to a deletion in mucA and functional N-acylhomoserine lactone (AHL)-based quorum-sensing systems. Chronic lung infection could be established in both CF...

  8. BDNF-Deficient Mice Show Reduced Psychosis-Related Behaviors Following Chronic Methamphetamine.

    Science.gov (United States)

    Manning, Elizabeth E; Halberstadt, Adam L; van den Buuse, Maarten

    2016-04-01

    One of the most devastating consequences of methamphetamine abuse is increased risk of psychosis. Brain-derived neurotrophic factor has been implicated in both psychosis and neuronal responses to methamphetamine. We therefore examined persistent psychosis-like behavioral effects of methamphetamine in brain-derived neurotrophic factor heterozygous mice. Mice were chronically treated with methamphetamine from 6 to 9 weeks of age, and locomotor hyperactivity to an acute D-amphetamine challenge was tested in photocell cages after a 2-week withdrawal period. Methamphetamine-treated wild-type mice, but not brain-derived neurotrophic factor heterozygous mice, showed locomotor sensitization to acute 3mg/kg D-amphetamine. Qualitative analysis of exploration revealed tolerance to D-amphetamine effects on entropy in methamphetamine-treated brain-derived neurotrophic factor heterozygous mice, but not wild-type mice. Chronic methamphetamine exposure induces contrasting profiles of behavioral changes in wild-type and brain-derived neurotrophic factor heterozygous mice, with attenuation of behaviors relevant to psychosis in methamphetamine-treated brain-derived neurotrophic factor heterozygous mice. This suggests that brain-derived neurotrophic factor signalling changes may contribute to development of psychosis in methamphetamine users. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  9. Phyllanthus species for chronic hepatitis B virus infection

    DEFF Research Database (Denmark)

    Yun, Xia; Luo, Hui; Liu, Jian Ping

    2011-01-01

    Phyllanthus species for patients with chronic hepatitis B virus (HBV) infection have been assessed in clinical trials, but no consensus regarding their usefulness exists.......Phyllanthus species for patients with chronic hepatitis B virus (HBV) infection have been assessed in clinical trials, but no consensus regarding their usefulness exists....

  10. Comparing the bacterial diversity of acute and chronic dental root canal infections.

    Directory of Open Access Journals (Sweden)

    Adriana L Santos

    Full Text Available This study performed barcoded multiplex pyrosequencing with a 454 FLX instrument to compare the microbiota of dental root canal infections associated with acute (symptomatic or chronic (asymptomatic apical periodontitis. Analysis of samples from 9 acute abscesses and 8 chronic infections yielded partial 16S rRNA gene sequences that were taxonomically classified into 916 bacterial species-level operational taxonomic units (OTUs (at 3% divergence belonging to 67 genera and 13 phyla. The most abundant phyla in acute infections were Firmicutes (52%, Fusobacteria (17% and Bacteroidetes (13%, while in chronic infections the dominant were Firmicutes (59%, Bacteroidetes (14% and Actinobacteria (10%. Members of Fusobacteria were much more prevalent in acute (89% than in chronic cases (50%. The most abundant/prevalent genera in acute infections were Fusobacterium and Parvimonas. Twenty genera were exclusively detected in acute infections and 18 in chronic infections. Only 18% (n = 165 of the OTUs at 3% divergence were shared by acute and chronic infections. Diversity and richness estimators revealed that acute infections were significantly more diverse than chronic infections. Although a high interindividual variation in bacterial communities was observed, many samples tended to group together according to the type of infection (acute or chronic. This study is one of the most comprehensive in-deep comparisons of the microbiota associated with acute and chronic dental root canal infections and highlights the role of diverse polymicrobial communities as the unit of pathogenicity in acute infections. The overall diversity of endodontic infections as revealed by the pyrosequencing technique was much higher than previously reported for endodontic infections.

  11. EcoHIV infection of mice establishes latent viral reservoirs in T cells and active viral reservoirs in macrophages that are sufficient for induction of neurocognitive impairment.

    Science.gov (United States)

    Gu, Chao-Jiang; Borjabad, Alejandra; Hadas, Eran; Kelschenbach, Jennifer; Kim, Boe-Hyun; Chao, Wei; Arancio, Ottavio; Suh, Jin; Polsky, Bruce; McMillan, JoEllyn; Edagwa, Benson; Gendelman, Howard E; Potash, Mary Jane; Volsky, David J

    2018-06-01

    Suppression of HIV replication by antiretroviral therapy (ART) or host immunity can prevent AIDS but not other HIV-associated conditions including neurocognitive impairment (HIV-NCI). Pathogenesis in HIV-suppressed individuals has been attributed to reservoirs of latent-inducible virus in resting CD4+ T cells. Macrophages are persistently infected with HIV but their role as HIV reservoirs in vivo has not been fully explored. Here we show that infection of conventional mice with chimeric HIV, EcoHIV, reproduces physiological conditions for development of disease in people on ART including immunocompetence, stable suppression of HIV replication, persistence of integrated, replication-competent HIV in T cells and macrophages, and manifestation of learning and memory deficits in behavioral tests, termed here murine HIV-NCI. EcoHIV established latent reservoirs in CD4+ T lymphocytes in chronically-infected mice but could be induced by epigenetic modulators ex vivo and in mice. In contrast, macrophages expressed EcoHIV constitutively in mice for up to 16 months; murine leukemia virus (MLV), the donor of gp80 envelope in EcoHIV, did not infect macrophages. Both EcoHIV and MLV were found in brain tissue of infected mice but only EcoHIV induced NCI. Murine HIV-NCI was prevented by antiretroviral prophylaxis but once established neither persistent EcoHIV infection in mice nor NCI could be reversed by long-acting antiretroviral therapy. EcoHIV-infected, athymic mice were more permissive to virus replication in macrophages than were wild-type mice, suffered cognitive dysfunction, as well as increased numbers of monocytes and macrophages infiltrating the brain. Our results suggest an important role of HIV expressing macrophages in HIV neuropathogenesis in hosts with suppressed HIV replication.

  12. Chronic consumption of distilled sugarcane spirit induces anxiolytic-like effects in mice.

    Science.gov (United States)

    Sena, Maria Clecia P; Nunes, Fabíola C; Salvadori, Mirian G S Stiebbe; Carvalho, Cleyton Charles D; Morais, Liana Clebia S L; Braga, Valdir A

    2011-01-01

    Chronic ethanol consumption is a major public health problem throughout the world. We investigated the anxiolytic-like effects and the possible ever injury induced by the chronic consumption of ethanol or sugarcane spirit in mice. Adult mice were exposed to a two-bottle free-choice paradigm for 6 weeks. The mice in Group A (n = 16) had access to sugarcane spirit + distilled water, the mice in Group B (n = 15) had access to ethanol + distilled water, and the mice in Group C (control, n = 14) had access to distilled water + distilled water. The ethanol content in the beverages offered to Groups A and B was 2% for the first week, 5% for the second week and 10% for the remaining four weeks. At the end of the experimental period, the mice were evaluated using the elevated-plus maze and the hole-board test to assess their anxiety-related behaviors. We also determined the serum aspartate aminotransferase and alanine aminotransferase levels. In the elevated-plus maze, the time spent in the open arms was increased in the mice exposed to chronic ethanol (32 ± 8 vs. 7 ± 2 s, n = 9) or sugarcane spirit (36 ± 9 vs. 7 ± 2 s, n = 9) compared to the controls. In the hole-board test, the mice exposed to ethanol or sugarcane spirit displayed increases in their head-dipping frequency (16 ± 1 for the control group, 27 ± 2 for the ethanol group, and 31 ± 3 for the sugarcane-spirit group; n = 9 for each group). In addition, the mice exposed to sugarcane spirit displayed an increase in the aspartate aminotransferase / alanine aminotransferase ratio compared to the ethanol group (1.29 ± 0.17 for the control group and 2.67 ± 0.17 for the sugarcane spirit group; n = 8 for each group). The chronic consumption of sugarcane-spirit produces liver injury and anxiolytic-like effects and the possible liver injury in mice.

  13. Chronic consumption of distilled sugarcane spirit induces anxiolytic-like effects in mice

    Directory of Open Access Journals (Sweden)

    Maria Clecia P. Sena

    2011-01-01

    Full Text Available OBJECTIVE: Chronic ethanol consumption is a major public health problem throughout the world. We investigated the anxiolytic-like effects and the possible ever injury induced by the chronic consumption of ethanol or sugarcane spirit in mice. METHOD: Adult mice were exposed to a two-bottle free-choice paradigm for 6 weeks. The mice in Group A (n = 16 had access to sugarcane spirit + distilled water, the mice in Group B (n = 15 had access to ethanol + distilled water, and the mice in Group C (control, n = 14 had access to distilled water + distilled water. The ethanol content in the beverages offered to Groups A and B was 2% for the first week, 5% for the second week and 10% for the remaining four weeks. At the end of the experimental period, the mice were evaluated using the elevated-plus maze and the hole-board test to assess their anxiety-related behaviors. We also determined the serum aspartate aminotransferase and alanine aminotransferase levels. RESULTS: In the elevated-plus maze, the time spent in the open arms was increased in the mice exposed to chronic ethanol (32 + 8 vs. 7 + 2 s, n = 9 or sugarcane spirit (36 + 9 vs. 7 + 2 s, n = 9 compared to the controls. In the hole-board test, the mice exposed to ethanol or sugarcane spirit displayed increases in their head-dipping frequency (16 + 1 for the control group, 27 + 2 for the ethanol group, and 31 + 3 for the sugarcane-spirit group; n = 9 for each group. In addition, the mice exposed to sugarcane spirit displayed an increase in the aspartate aminotransferase / alanine aminotransferase ratio compared to the ethanol group (1.29 + 0.17 for the control group and 2.67 + 0.17 for the sugarcane spirit group; n = 8 for each group. CONCLUSION: The chronic consumption of sugarcane-spirit produces liver injury and anxiolytic-like effects and the possible liver injury in mice.

  14. MicroRNA-155 knockout mice are susceptible to Mycobacterium tuberculosis infection.

    Science.gov (United States)

    Iwai, Hiroki; Funatogawa, Keiji; Matsumura, Kazunori; Kato-Miyazawa, Masako; Kirikae, Fumiko; Kiga, Kotaro; Sasakawa, Chihiro; Miyoshi-Akiyama, Tohru; Kirikae, Teruo

    2015-05-01

    MicroRNAs (miRNAs) are short, conserved, non-coding RNA molecules that repress translation, followed by the decay of miRNA-targeted mRNAs that encode molecules involved in cell differentiation, development, immunity and apoptosis. At least six miRNAs, including microRNA-155 (miR-155), were up-regulated when born marrow-derived macrophages from C57BL/6 mice were infected with Mycobacterium tuberculosis Erdman. C57BL/6 mice intravenously infected with Erdman showed up-regulation of miR-155 in livers and lungs. Following infection, miR-155-deficient C57BL/6 mice died significantly earlier and had significantly higher numbers of CFU in lungs than wild-type mice. Moreover, fewer CD4(+) T cells, but higher numbers of monocytes and neutrophils, were present in the lungs of Erdman-infected miR-155 knockout (miR-155(-/-)) than of wild-type mice. These findings indicated that miR-155 plays a critical role in immune responses to M. tuberculosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. CISH controls bacterial burden early after infection with Mycobacterium tuberculosis in mice.

    Science.gov (United States)

    Carow, Berit; Gao, Yu; Terán, Graciela; Yang, Xuexian O; Dong, Chen; Yoshimura, Akihiko; Rottenberg, Martin E

    2017-12-01

    CISH gene has been associated with increased susceptibility to human tuberculosis. We found that cish -/- mice had higher M. tuberculosis load in spleens and lungs up to 2.5 weeks after infection but not later compared to controls. Cish mRNA levels were increased in lungs at early and late time points after M. tuberculosis infection. In relation, the titers of inos and tnf mRNA in lungs were reduced early after infection of cish -/- mice. The transfer of cish -/- and control T cells conferred rag1 -/- mice similar protection to infection with M. tuberculosis. Macrophages showed increased cish mRNA levels after M. tuberculosis infection in vitro. However, mycobacterial uptake and growth in cish -/- and control macrophages was similar. Thus, we here show that CISH mediates control of M. tuberculosis in mice early after infection via regulation of innate immune mechanisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Middle Ear Infection (Chronic Otitis Media) and Hearing Loss

    Science.gov (United States)

    ... ENT Doctor Near You Middle Ear Infection (Chronic Otitis Media) and Hearing Loss Middle Ear Infection (Chronic ... relations staff at newsroom@entnet.org . What is otitis media? Otitis media refers to inflammation of the ...

  17. Immune regulation in Chandipura virus infection: characterization of CD4+ T regulatory cells from infected mice

    Directory of Open Access Journals (Sweden)

    Shahir Prajakta

    2011-05-01

    Full Text Available Abstract Back ground Chandipura virus produces acute infection in mice. During infection drastic reduction of CD4+, CD8+ and CD19 + cell was noticed. Depletion of lymphocytes also noticed in spleen. The reduction may be due to the regulatory mechanism of immune system to prevent the bystander host tissue injury. There are several mechanisms like generation of regulatory cells, activation induced cell death (ACID etc were indicated to control the activation and maintain cellular homeostasis. Role of regulatory cells in homeostasis has been described in several viral diseases. This study was undertaken to characterize CD4+T regulatory cells from the infected mice. Method In this study we purified the CD4+ T cells from Chandipura virus infected susceptible Balb/c mice. CD4+ T regulatory cells were identified by expression of cell surface markers CD25, CD127 and CTLA-4 and intracellular markers Foxp3, IL-10 and TGF-beta. Antigen specificity and ability to suppress the proliferation of other lymphocytes were studied in vitro by purified CD4+CD25+T regulatory cells from infected mice. The proliferation was calculated by proliferation module of Flow Jo software. Expression of death receptors on regulatory cells were studied by flowcytometer. Results The CD4+ T cells isolated from infected mice expressed characteristic markers of regulatory phenotype at all post infective hours tested. The CD4+ T regulatory cells were proliferated when stimulated with Chandipura virus antigen. The regulatory cells did not suppress the proliferation of splenocytes stimulated with anti CD3 antibody when co cultured with them. Interesting observation was, while purification of CD4+ T cells by negative selection, the population of cells negative for CD4 also co purified along with CD4+ T cell. Flow cytometry analysis and light microscopy revealed that CD4 negative cells were of different size and shape (atypical compared to the normal lymphocytes. Greater percentage of

  18. Clearance of Giardia muris infection in mice deficient in natural killer cells.

    OpenAIRE

    Heyworth, M F; Kung, J E; Eriksson, E C

    1986-01-01

    Immunocompetent C57BL/6J mice and beige mice (which are deficient in natural killer cells) were infected with Giardia muris. Both types of mice cleared G. muris infection at similar rates. This observation suggests that clearance of G. muris parasites from the mouse intestine is not mediated by natural killer cells.

  19. Activity of nucleic acid polymers in rodent models of HBV infection.

    Science.gov (United States)

    Schöneweis, Katrin; Motter, Neil; Roppert, Pia L; Lu, Mengji; Wang, Baoju; Roehl, Ingo; Glebe, Dieter; Yang, Dongliang; Morrey, John D; Roggendorf, Michael; Vaillant, Andrew

    2018-01-01

    Nucleic acid polymers (NAPs) block the release of HBsAg from infected hepatocytes. These compounds have been previously shown to have the unique ability to eliminate serum surface antigen in DHBV-infected Pekin ducks and achieve multilog reduction of HBsAg or HBsAg loss in patients with chronic HBV infection and HBV/HDV coinfection. In ducks and humans, the blockage of HBsAg release by NAPs occurs by the selective targeting of the assembly and/or secretion of subviral particles (SVPs). The clinically active NAP species REP 2055 and REP 2139 were investigated in other relevant animal models of HBV infection including woodchucks chronically infected with WHV, HBV transgenic mice and HBV infected SCID-Hu mice. The liver accumulation of REP 2139 in woodchucks following subcutaneous administration was examined and was found to be similar to that observed in mice and ducks. However, in woodchucks, NAP treatment was associated with only mild (36-79% relative to baseline) reductions in WHsAg (4/10 animals) after 3-5 weeks of treatment without changes in serum WHV DNA. In HBV infected SCID-Hu mice, REP 2055 treatment was not associated with any reduction of HBsAg, HBeAg or HBV DNA in the serum after 28 days of treatment. In HBV transgenic mice, no reductions in serum HBsAg were observed with REP 2139 with up to 12 weeks of treatment. In conclusion, the antiviral effects of NAPs in DHBV infected ducks and patients with chronic HBV infection were weak or absent in woodchuck and mouse models despite similar liver accumulation of NAPs in all these species, suggesting that the mechanisms of SVP assembly and or secretion present in rodent models differs from that in DHBV and chronic HBV infections. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  20. Increased susceptibility to Yersinia enterocolitica Infection of Tff2 deficient mice.

    Science.gov (United States)

    Shah, Aftab A; Mihalj, Martina; Ratkay, Ivana; Lubka-Pathak, Maria; Balogh, Peter; Klingel, Karin; Bohn, Erwin; Blin, Nikolaus; Baus-Loncar, Mirela

    2012-01-01

    TFF2 is one of the members of the trefoil factor family, known for its role in protection of gastrointestinal epithelia upon injury; however, recent studies suggest that TFF2 could also play an important role in the immune system. In the present study Tff2 deficient and wild type mice were infected by Y. enterocolitica which resulted in a lethal outcome in all Tff2 deficient mice, but not in WT animals. Yersinia invaded Peyer's patches more efficiently as shown by high bacterial titers in the KO mice while wild type mice displayed lower titers and a visible bacterial accumulation in the intestine. Bacterial accumulation in Peyer's patches of Tff2 deficient mice was accompanied by increased recruitment of macrophages. While an increased level of MAC-1 positive cells was observed in the spleens of both Tff2 deficient and WT mice at third day post infection, bacterial dissemination to liver, lung and kidneys was observed only in Tff2 knock-out mice. Analysis of the cellular composition of spleen did not reveal any substantial alteration to WT animals, suggesting possible disregulation of hemopoietic cells involved in immune response to Y. enterocolitica. These new data indicate that Tff2 plays an important role in immune response by protecting the organism from consequences of infection and that Tff2 knock-out mice react adversely to bacterial infections, in this case specifically to Y. enterocolitica. Copyright © 2012 S. Karger AG, Basel.

  1. Late effects of chronic low dose-rate γ-rays irradiation on mice

    International Nuclear Information System (INIS)

    Tanaka, Satoshi; Sasagawa, Sumiko; Ichinohe, Kazuaki; Matsumoto, Tsuneya; Otsu, Hiroshi; Sato, Fumiaki

    2002-01-01

    To evaluate late biological effects of chronic low dose-rate radiation, we are conducting two experiments. Experiment 1 - Late effects of chronic low dose-rate g-rays irradiation on SPF mice, using life-span and pathological changes as parameters. Continuous irradiation with g-rays for 400 days was performed using 137 Cs γ-rays at dose-rates of 20 mGy/day, 1 mGy/day and 0.05 mGy/day with accumulated doses equivalent to 8,000 mGy, 400 mGy and 20 mGy, respectively. All mice were kept until they died a natural death. As of 2002 March 31, 3,999 of the total 4,000 mice have died. Preliminary analyses of data show that 20 mGy/day suggested a shortened life span in both sexes. Partial results show that the most common lethal neoplasms in the pooled data of non-irradiated control and irradiated male mice, in order of frequency, were neoplasms of the lymphohematopoietic system, liver, and lung. In female mice, neoplasms of the lymphohematopoietic system, soft tissue, and endocrine system were common. Experiment 2 - Effects on the progeny of chronic low dose-rate g-ray irradiated SPF mice: pilot study, was started in 1999 and is currently in progress. (author)

  2. Detection of prion infectivity in fat tissues of scrapie-infected mice.

    Directory of Open Access Journals (Sweden)

    Brent Race

    2008-12-01

    Full Text Available Distribution of prion infectivity in organs and tissues is important in understanding prion disease pathogenesis and designing strategies to prevent prion infection in animals and humans. Transmission of prion disease from cattle to humans resulted in banning human consumption of ruminant nervous system and certain other tissues. In the present study, we surveyed tissue distribution of prion infectivity in mice with prion disease. We show for the first time detection of infectivity in white and brown fat. Since high amounts of ruminant fat are consumed by humans and also incorporated into animal feed, fat-containing tissues may pose a previously unappreciated hazard for spread of prion infection.

  3. Parasitic infection improves survival from septic peritonitis by enhancing mast cell responses to bacteria in mice.

    Directory of Open Access Journals (Sweden)

    Rachel E Sutherland

    Full Text Available Mammals are serially infected with a variety of microorganisms, including bacteria and parasites. Each infection reprograms the immune system's responses to re-exposure and potentially alters responses to first-time infection by different microorganisms. To examine whether infection with a metazoan parasite modulates host responses to subsequent bacterial infection, mice were infected with the hookworm-like intestinal nematode Nippostrongylus brasiliensis, followed in 2-4 weeks by peritoneal injection of the pathogenic bacterium Klebsiella pneumoniae. Survival from Klebsiella peritonitis two weeks after parasite infection was better in Nippostrongylus-infected animals than in unparasitized mice, with Nippostrongylus-infected mice having fewer peritoneal bacteria, more neutrophils, and higher levels of protective interleukin 6. The improved survival of Nippostrongylus-infected mice depends on IL-4 because the survival benefit is lost in mice lacking IL-4. Because mast cells protect mice from Klebsiella peritonitis, we examined responses in mast cell-deficient Kit(W-sh/Kit(W-sh mice, in which parasitosis failed to improve survival from Klebsiella peritonitis. However, adoptive transfer of cultured mast cells to Kit(W-sh/Kit(W-sh mice restored survival benefits of parasitosis. These results show that recent infection with Nippostrongylus brasiliensis protects mice from Klebsiella peritonitis by modulating mast cell contributions to host defense, and suggest more generally that parasitosis can yield survival advantages to a bacterially infected host.

  4. Middle Ear Infection (Chronic Otitis Media) and Hearing Loss

    Science.gov (United States)

    ... Marketplace Find an ENT Doctor Near You Middle Ear Infection (Chronic Otitis Media) and Hearing Loss Middle Ear Infection (Chronic Otitis ... relations staff at newsroom@entnet.org . What is otitis media? Otitis media refers to inflammation of the middle ...

  5. Immune regulation in chronic hepatitis C virus infection

    DEFF Research Database (Denmark)

    Hartling, Hans Jakob; Ballegaard, Vibe Cecilie; Nielsen, Nick Schou

    2016-01-01

    The immunological result of infection with Hepatitis C virus (HCV) depends on the delicate balance between a vigorous immune response that may clear the infection, but with a risk of unspecific inflammation and, or a less inflammatory response that leads to chronic infection. In general, exhaustion...... and impairment of cytotoxic function of HCV-specific T cells and NK cells are found in patients with chronic HCV infection. In contrast, an increase in immune regulatory functions is found primarily in form of increased IL-10 production possibly due to increased level and function of anti-inflammatory Tregs...

  6. Effects of acute and chronic psychological stress on platelet aggregation in mice.

    Science.gov (United States)

    Matsuhisa, Fumikazu; Kitamura, Nobuo; Satoh, Eiki

    2014-03-01

    Although psychological stress has long been known to alter cardiovascular function, there have been few studies on the effect of psychological stress on platelets, which play a pivotal role in cardiovascular disease. In the present study, we investigated the effects of acute and chronic psychological stress on the aggregation of platelets and platelet cytosolic free calcium concentration ([Ca(2+)]i). Mice were subjected to both transportation stress (exposure to novel environment, psychological stress) and restraint stress (psychological stress) for 2 h (acute stress) or 3 weeks (2 h/day) (chronic stress). In addition, adrenalectomized mice were subjected to similar chronic stress (both transportation and restraint stress for 3 weeks). The aggregation of platelets from mice and [Ca(2+)]i was determined by light transmission assay and fura-2 fluorescence assay, respectively. Although acute stress had no effect on agonist-induced platelet aggregation, chronic stress enhanced the ability of the platelet agonists thrombin and ADP to stimulate platelet aggregation. However, chronic stress failed to enhance agonist-induced increase in [Ca(2+)]i. Adrenalectomy blocked chronic stress-induced enhancement of platelet aggregation. These results suggest that chronic, but not acute, psychological stress enhances agonist-stimulated platelet aggregation independently of [Ca(2+)]i increase, and the enhancement may be mediated by stress hormones secreted from the adrenal glands.

  7. Virus Infections on Prion Diseased Mice Exacerbate Inflammatory Microglial Response

    Science.gov (United States)

    Lins, Nara; Mourão, Luiz; Trévia, Nonata; Passos, Aline; Farias, José Augusto; Assunção, Jarila; Bento-Torres, João; Consentino Kronka Sosthenes, Marcia; Diniz, José Antonio Picanço; Vasconcelos, Pedro Fernando da Costa

    2016-01-01

    We investigated possible interaction between an arbovirus infection and the ME7 induced mice prion disease. C57BL/6, females, 6-week-old, were submitted to a bilateral intrahippocampal injection of ME7 prion strain (ME7) or normal brain homogenate (NBH). After injections, animals were organized into two groups: NBH (n = 26) and ME7 (n = 29). At 15th week after injections (wpi), animals were challenged intranasally with a suspension of Piry arbovirus 0.001% or with NBH. Behavioral changes in ME7 animals appeared in burrowing activity at 14 wpi. Hyperactivity on open field test, errors on rod bridge, and time reduction in inverted screen were detected at 15th, 19th, and 20th wpi respectively. Burrowing was more sensitive to earlier hippocampus dysfunction. However, Piry-infection did not significantly affect the already ongoing burrowing decline in the ME7-treated mice. After behavioral tests, brains were processed for IBA1, protease-resistant form of PrP, and Piry virus antigens. Although virus infection in isolation did not change the number of microglia in CA1, virus infection in prion diseased mice (at 17th wpi) induced changes in number and morphology of microglia in a laminar-dependent way. We suggest that virus infection exacerbates microglial inflammatory response to a greater degree in prion-infected mice, and this is not necessarily correlated with hippocampal-dependent behavioral deficits. PMID:28003864

  8. NLRP3 Controls the Development of Gastrointestinal CD11b+ Dendritic Cells in the Steady State and during Chronic Bacterial Infection

    Directory of Open Access Journals (Sweden)

    Isabelle C. Arnold

    2017-12-01

    Full Text Available The gastric lamina propria is largely uncharted immunological territory. Here we describe the evolution and composition of the gastric, small intestinal, and colonic lamina propria mononuclear phagocyte system during the steady state and infection with the gastric pathogen Helicobacter pylori. We show that monocytes, CX3CR1hi macrophages, and CD11b+ dendritic cells are recruited to the infected stomach in a CCR2-dependent manner. All three populations, but not BATF3-dependent CD103+ DCs, sample red fluorescent protein (RFP+ Helicobacter pylori (H. pylori. Mice reconstituted with human hematopoietic stem cells recapitulate several features of the myeloid cell-H. pylori interaction. The differentiation in and/or recruitment to gastrointestinal, lung, and lymphoid tissues of CD11b+ DCs requires NLRP3, but not apoptosis-associated speck-like protein containing a carboxy-terminal CARD (ASC or caspase-1, during steady-state and chronic infection. NLRP3−/− mice fail to generate Treg responses to H. pylori and control the infection more effectively than wild-type mice. The results demonstrate a non-canonical inflammasome-independent function of NLRP3 in DC development and immune regulation.

  9. Pretreatment of Mice with Oligonucleotide prop5 Protects Them from Influenza Virus Infections

    Directory of Open Access Journals (Sweden)

    Kang Li

    2014-02-01

    Full Text Available Influenza A virus is a successful parasite and requires host factors to complete its life cycle. Prop5 is an antisense oligonucleotide, targeting programmed cell death protein 5 (PDCD5. In this study, we tested the antiviral activity of prop5 against mouse-adapted A/FM/1/47 strain of influenza A virus in a mouse model. Prop5 intranasally administered the mice at dosages of 10 and 20 mg/kg/d at 24 h and 30 min before infection, provided 80% and 100% survival rates and prolonged mean survival days in comparison with influenza virus-infected mice (both p < 0.01. Moreover, viral titres in mice pretreated with prop5, at dose of 10 and 20 mg/kg/d, had declined significantly on day two, four, and six post-infection compared with the yields in infected mice (p < 0.05 or p < 0.01; lung index in mice pretreated with prop5 (20 mg/kg/d had been inhibited on day six post-infection (p < 0.05. Western blotting and immunohistochemistry showed that prop5 could down-regulate the PDCD5 protein expression levels in lung tissues of infected mice. These data indicate that antisense oligonucleotide prop5 is a promising drug for prophylaxis and control influenza virus infections and provides an insight into the host-pathogen interaction.

  10. Chandipura Virus infection in mice: the role of toll like receptor 4 in pathogenesis

    Directory of Open Access Journals (Sweden)

    Anukumar Balakrishnan

    2012-05-01

    Full Text Available Abstract Background The susceptibility of mice and humans to Chandipura virus infection is age-dependent. Upon experimental infection, mice secrete significant amounts of proinflammatory cytokines. Similarly, children who recover from natural infection with the virus show significant amounts of TNF-α production, suggesting that innate immunity plays a major role in the response to Chandipura virus. Toll-like receptors (TLR are key host molecules involved in innate immune responses in infections. Therefore, the aim of this study was to examine the role of TLR in the response to Chandipura virus infection. Methods The mouse monocyte-macrophage cell line, RAW 264.7, and C3H/HeJ mice were used as models. Micro array techniques were used to identify the type of TLR involved in the response to infection. The results were validated by examining TLR expression using flow cytometry and by measuring the levels of proinflammatory cytokines and nitric oxide (NO in the culture supernatants using bead assays and the Griess method, respectively. The pathogenic role of Toll-like receptor 4 (TLR4 was studied in a TLR4 mutant strain of mice -C3H/HeJ and the results compared with those from wild-type mice- C3H/CaJ. The pathogenic effects of NO were studied by treating experimentally infected mice with the NO inhibitor, aminoguanidine (AG. Results The micro array results showed that TLR4 was regulated after Chandipura virus infection. At high multiplicities of infection (10 MOI, RAW cells up- regulated cell surface expression of TLR4 and secreted significant amounts of TNF-α, MCP-1, IL-10 and IL-12 and NO. The survival rate of C3H/HeJ mice was higher than those of wild-type C3H/CaJ mice. The survived C3H/HeJ mice secreted significant quantity of MCP-1 and IFN-γ cytokines and cleared virus from brain. Similarly, the survival rate of AG-treated mice was higher than those of the untreated controls. Conclusions Chandipura virus regulates TLR4, which leads to the

  11. Differential pulmonic NK and NKT cell responses in Schistosoma japonicum-infected mice.

    Science.gov (United States)

    Cha, Hefei; Qin, Wenjuan; Yang, Quan; Xie, Hongyan; Qu, Jiale; Wang, Mei; Chen, Daixiong; Wang, Fang; Dong, Nuo; Chen, Longhua; Huang, Jun

    2017-02-01

    Natural killer cells (NK cells) and natural killer T cells (NKT cells) play a role in anti-infection, anti-tumor, transplantation immunity, and autoimmune regulation. However, the role of NK and NKT cells during Schistosoma japonicum (S. japonicum) infection has not been widely reported, especially regarding lung infections. The aim of this study was to research the NK and NKT cell response to S. japonicum infection in the lungs of mice. Using immunofluorescent histological analysis, NK and NKT cells were found near pulmonary granulomas. Moreover, flow cytometry revealed that the percentage and number of pulmonic NK cells in S. japonicum-infected mice were significantly increased (P cell number of NKT cells were decreased compared to those of normal mice (P NKT cells was increased after infection (P NKT cells (P cells (P NKT cells significantly increased (P NKT cells (P NKT cell activation during S. japonicum infection.

  12. TLR3 deficiency renders astrocytes permissive to herpes simplex virus infection and facilitates establishment of CNS infection in mice

    DEFF Research Database (Denmark)

    Reinert, Line; Harder, Louis Andreas; Holm, Christian

    2012-01-01

    Herpes simplex viruses (HSVs) are highly prevalent neurotropic viruses. While they can replicate lytically in cells of the epithelial lineage, causing lesions on mucocutaneous surfaces, HSVs also establish latent infections in neurons, which act as reservoirs of virus for subsequent reactivation......, it is not known what cell type mediates the role of TLR3 in the immunological control of HSV, and it is not known whether TLR3 sensing occurs prior to or after CNS entry. Here, we show that in mice TLR3 provides early control of HSV-2 infection immediately after entry into the CNS by mediating type I IFN...... responses in astrocytes. Tlr3-/- mice were hypersusceptible to HSV-2 infection in the CNS after vaginal inoculation. HSV-2 exhibited broader neurotropism in Tlr3-/- mice than it did in WT mice, with astrocytes being most abundantly infected. Tlr3-/- mice did not exhibit a global defect in innate immune...

  13. Chronic nicotine differentially alters spontaneous recovery of contextual fear in male and female mice.

    Science.gov (United States)

    Tumolo, Jessica M; Kutlu, Munir Gunes; Gould, Thomas J

    2018-04-02

    Post-traumatic stress disorder (PTSD) is a devastating disorder with symptoms such as flashbacks, hyperarousal, and avoidance of reminders of the traumatic event. Exposure therapy, which attempts to extinguish fear responses, is a commonly used treatment for PTSD but relapse following successful exposure therapy is a frequent problem. In rodents, spontaneous recovery (SR), where extinguished fear responses resurface following extinction treatment, is used as a model of fear relapse. Previous studies from our lab showed that chronic nicotine impaired fear extinction and acute nicotine enhanced SR of contextual fear in adult male mice. In addition, we showed that acute nicotine's effects were specific to SR as acute nicotine did not affect recall of contextual fear conditioning in the absence of extinction. However, effects of chronic nicotine administration on SR are not known. Therefore, in the present study, we investigated if chronic nicotine administration altered SR or recall of contextual fear in adult male and female C57BL/6J mice. Our results showed that chronic nicotine significantly enhanced SR in female mice and significantly decreased SR in males. Chronic nicotine had no effect on recall of contextual fear in males or females. Female sham mice also had significantly less baseline SR than male sham mice. Overall, these results demonstrate sex differences in SR of fear memories and that chronic nicotine modulates these effects on SR but nicotine does not alter recall of contextual fear. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Agmatine attenuates chronic unpredictable mild stress induced behavioral alteration in mice.

    Science.gov (United States)

    Taksande, Brijesh G; Faldu, Dharmesh S; Dixit, Madhura P; Sakaria, Jay N; Aglawe, Manish M; Umekar, Milind J; Kotagale, Nandkishor R

    2013-11-15

    Chronic stress exposure and resulting dysregulation of the hypothalamic pituitary adrenal axis develops susceptibility to variety of neurological and psychiatric disorders. Agmatine, a putative neurotransmitter has been reported to be released in response to various stressful stimuli to maintain the homeostasis. Present study investigated the role of agmatine on chronic unpredictable mild stress (CUMS) induced behavioral and biochemical alteration in mice. Exposure of mice to CUMS protocol for 28 days resulted in diminished performance in sucrose preference test, splash test, forced swim test and marked elevation in plasma corticosterone levels. Chronic agmatine (5 and 10 mg/kg, ip, once daily) treatment started on day-15 and continued till the end of the CUMS protocol significantly increased sucrose preference, improved self-care and motivational behavior in the splash test and decreased duration of immobility in the forced swim test. Agmatine treatment also normalized the elevated corticosterone levels and prevented the body weight changes in chronically stressed animals. The pharmacological effect of agmatine was comparable to selective serotonin reuptake inhibitor, fluoxetine (10mg/kg, ip). Results of present study clearly demonstrated the anti-depressant like effect of agmatine in chronic unpredictable mild stress induced depression in mice. Thus the development of drugs based on brain agmatinergic modulation may represent a new potential approach for the treatment of stress related mood disorders like depression. © 2013 Published by Elsevier B.V.

  15. Zika virus infection confers protection against West Nile virus challenge in mice.

    Science.gov (United States)

    Vázquez-Calvo, Ángela; Blázquez, Ana-Belén; Escribano-Romero, Estela; Merino-Ramos, Teresa; Saiz, Juan-Carlos; Martín-Acebes, Miguel A; Jiménez de Oya, Nereida

    2017-09-20

    Flaviviruses are RNA viruses that constitute a worrisome threat to global human and animal health. Zika virus (ZIKV), which was initially reported to cause a mild disease, recently spread in the Americas, infecting millions of people. During this recent epidemic, ZIKV infection has been linked to serious neurological diseases and birth defects, specifically Guillain-Barrè syndrome (GBS) and microcephaly. Because information about ZIKV immunity remains scarce, we assessed the humoral response of immunocompetent mice to infection with three viral strains of diverse geographical origin (Africa, Asia and America). No infected animals showed any sign of disease or died after infection. However, specific neutralizing antibodies were elicited in all infected mice. Considering the rapid expansion of ZIKV throughout the American continent and its co-circulation with other medically relevant flaviviruses, such as West Nile virus (WNV), the induction of protective immunity between ZIKV and WNV was analyzed. Remarkably, protection after challenge with WNV was observed in mice previously infected with ZIKV, as survival rates were significantly higher than in control mice. Moreover, previous ZIKV infection enhanced the humoral immune response against WNV. These findings may be relevant in geographical areas where both ZIKV and WNV co-circulate, as well as for the future development of broad-spectrum flavivirus vaccines.

  16. Th2 Regulation of Viral Myocarditis in Mice: Different Roles for TLR3 versus TRIF in Progression to Chronic Disease

    Directory of Open Access Journals (Sweden)

    Eric D. Abston

    2012-01-01

    Full Text Available Viral infections are able to induce autoimmune inflammation in the heart. Here, we investigated the role of virus-activated Toll-like receptor (TLR3 and its adaptor TRIF on the development of autoimmune coxsackievirus B3 (CVB3 myocarditis in mice. Although TLR3- or TRIF-deficient mice developed similarly worse acute CVB3 myocarditis and viral replication compared to control mice, disease was significantly worse in TRIF compared to TLR3-deficient mice. Interestingly, TLR3-deficient mice developed an interleukin (IL-4-dominant T helper (Th2 response during acute CVB3 myocarditis with elevated markers of alternative activation, while TRIF-deficient mice elevated the Th2-associated cytokine IL-33. Treatment of TLR3-deficient mice with recombinant IL-33 improved heart function indicating that elevated IL-33 in the context of a classic Th2-driven response protects against autoimmune heart disease. We show for the first time that TLR3 versus TRIF deficiency results in different Th2 responses that uniquely influence the progression to chronic myocarditis.

  17. [Infected knee prostheses. Part 2: chronic late infections].

    Science.gov (United States)

    Herrmann, P; Thoele, P; Heppert, V

    2013-06-01

    Treatment of late and chronic infections, which require the replacement of all the infected implant material. All infections lasting more than 4 weeks that have been proven to be bacterial and/or obvious signs of infection. Unsuitable for anesthesia, high acute infection with sepsis and risk for bacteremia with danger to life, large soft tissue damage where plastic surgery coverage is not possible. Arthrotomy, synovectomy, removal of all foreign bodies including all residue of polymethylmethacrylate (PMMA), jet lavage, spacer, drainage, wound closure or temporary closure using vacuum sealing. Bed rest with a leg brace and drainage until daily drainage volume is exchange of the spacer. In the literature, the success rate for both the one-stage or the two-stage procedure is about 80-95%. In our very nonhomogeneous collective the overall rate of success is about 81%.

  18. Chronic Posttraumatic Epilepsy following Neocortical Undercut Lesion in Mice.

    Directory of Open Access Journals (Sweden)

    Xingjie Ping

    Full Text Available Posttraumatic epilepsy (PTE usually develops in a small percentage of patients of traumatic brain injury after a varying latent period. Modeling this chronic neurological condition in rodents is time consuming and inefficient, which constitutes a significant obstacle in studying its mechanism and discovering novel therapeutics for its prevention and treatment. Partially isolated neocortex, or undercut, is known to induce cortical hyperexcitability and epileptiform activity in vitro, and has been used extensively for studying the neurophysiological mechanism of posttraumatic epileptogenesis. However, whether the undercut lesion in rodents causes chronic epileptic seizures has not been systematically characterized. Here we used a miniature telemetry system to continuously monitor electroencephalography (EEG in adult C57BL mice for up to 3 months after undercut surgery. We found that 50% of animals developed spontaneous seizures between 16-50 days after injury. The mean seizure duration was 8.9±3.6 seconds, and the average seizure frequency was 0.17±0.17 times per day. There was no progression in seizure frequency and duration over the recording period. Video monitoring revealed behavioral arrests and clonic limb movement during seizure attacks. A pentylenetetrazol (PTZ test further showed increased seizure susceptibility in the undercut mice. We conclude that undercut lesion in mice is a model of chronic PTE that involves spontaneous epileptic seizures.

  19. Targeted photodynamic therapy of established soft-tissue infections in mice

    Science.gov (United States)

    Gad, Faten; Zahra, Touqir; Hasan, Tayyaba; Hamblin, Michael R.

    2004-06-01

    The worldwide rise in antibiotic resistance necessitates the development of novel antimicrobial strategies. Although many workers have used photodynamic therapy (PDT) to kill bacteria in vitro, the use of this approach has seldom been reported in vivo in animal models of infection. We have previously described the first use of PDT to treat excisional wound infections by Gram-negative bacteria in living mice. However these infected wound models used a short time after infection (30 min) before PDT. We now report on the use of PDT to treat an established soft-tissue infection in mice. We used Staphylococcus aureus stably transformed with a Photorhabdus luminescens lux operon (luxABCDE) that was genetically modified to be functional in Gram-positive bacteria. These engineered bacteria emitted bioluminescence allowing the progress of the infection to be monitored in both space and time with a lowlight imaging charged couple device (CCD) camera. One million cells were injected into one or both thigh muscles of mice that had previously been rendered neutropenic by cyclophosphamide administration. Twenty-four hours later the bacteria had multiplied more than one hundred-fold, and poly-L-lysine chlorin(e6) conjugate or free chlorin(e6) was injected into one area of infected muscle and imaged with the CCD camera. Thirty-minutes later red light from a diode laser was delivered as a surface spot or by interstitial fiber into the infection. There was a lightdose dependent loss of bioluminescence (to resistant soft-tissue infections.

  20. Visual and Motor Deficits in Grown-up Mice with Congenital Zika Virus Infection

    Directory of Open Access Journals (Sweden)

    Liyuan Cui

    2017-06-01

    Full Text Available Human infants with congenital Zika virus (ZIKV infection exhibit a range of symptoms including microcephaly, intracranial calcifications, macular atrophy and arthrogryposis. More importantly, prognosis data have lagged far behind the recent outbreak of ZIKV in 2015. In this work, we allow congenitally ZIKV-infected mice to grow into puberty. These mice exhibited motor incoordination and visual dysfunctions, which can be accounted by anatomical defects in the retina and cerebellar cortex. In contrary, anxiety level of the ZIKV-infected mice is normal. The spectrum of anatomical and behavioral deficits is consistent across different mice. Our data provided evidence that may help predict the public health burden in terms of prognosis of ZIKV-related congenital brain malformations in an animal model. Our study provided behavioral evaluation for the prognosis of congenital ZIKV infection and provides a platform for screening and evaluation of drugs candidates and treatment aiming at improving regeneration of infected neurons to prevent sequelae caused by ZIKV infection of fetus.

  1. Chronic exposure to low frequency noise at moderate levels causes impaired balance in mice.

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    Haruka Tamura

    Full Text Available We are routinely exposed to low frequency noise (LFN; below 0.5 kHz at moderate levels of 60-70 dB sound pressure level (SPL generated from various sources in occupational and daily environments. LFN has been reported to affect balance in humans. However, there is limited information about the influence of chronic exposure to LFN at moderate levels for balance. In this study, we investigated whether chronic exposure to LFN at a moderate level of 70 dB SPL affects the vestibule, which is one of the organs responsible for balance in mice. Wild-type ICR mice were exposed for 1 month to LFN (0.1 kHz and high frequency noise (HFN; 16 kHz at 70 dB SPL at a distance of approximately 10-20 cm. Behavior analyses including rotarod, beam-crossing and footprint analyses showed impairments of balance in LFN-exposed mice but not in non-exposed mice or HFN-exposed mice. Immunohistochemical analysis showed a decreased number of vestibular hair cells and increased levels of oxidative stress in LFN-exposed mice compared to those in non-exposed mice. Our results suggest that chronic exposure to LFN at moderate levels causes impaired balance involving morphological impairments of the vestibule with enhanced levels of oxidative stress. Thus, the results of this study indicate the importance of considering the risk of chronic exposure to LFN at a moderate level for imbalance.

  2. Impaired Latent Inhibition in GDNF-Deficient Mice Exposed to Chronic Stress

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    Mona Buhusi

    2017-10-01

    Full Text Available Increased reactivity to stress is maladaptive and linked to abnormal behaviors and psychopathology. Chronic unpredictable stress (CUS alters catecholaminergic neurotransmission and remodels neuronal circuits involved in learning, attention and decision making. Glial-derived neurotrophic factor (GDNF is essential for the physiology and survival of dopaminergic neurons in substantia nigra and of noradrenergic neurons in the locus coeruleus. Up-regulation of GDNF expression during stress is linked to resilience; on the other hand, the inability to up-regulate GDNF in response to stress, as a result of either genetic or epigenetic modifications, induces behavioral alterations. For example, GDNF-deficient mice exposed to chronic stress exhibit alterations of executive function, such as increased temporal discounting. Here we investigated the effects of CUS on latent inhibition (LI, a measure of selective attention and learning, in GDNF-heterozygous (HET mice and their wild-type (WT littermate controls. No differences in LI were found between GDNF HET and WT mice under baseline experimental conditions. However, following CUS, GDNF-deficient mice failed to express LI. Moreover, stressed GDNF-HET mice, but not their WT controls, showed decreased neuronal activation (number of c-Fos positive neurons in the nucleus accumbens shell and increased activation in the nucleus accumbens core, both key regions in the expression of LI. Our results add LI to the list of behaviors affected by chronic stress and support a role for GDNF deficits in stress-induced pathological behaviors relevant to schizophrenia and other psychiatric disorders.

  3. Aspirin attenuates spontaneous recurrent seizures in the chronically epileptic mice.

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    Zhu, Kun; Hu, Ming; Yuan, Bo; Liu, Jian-Xin; Liu, Yong

    2017-08-01

    Neuroinflammatory processes are pathologic hallmarks of both experimental and human epilepsy, and could be implicated in the neuronal hyperexcitability. Aspirin represents one of the non-selective nonsteroidal anti-inflammatory drugs with fewer side effects in long-term application. This study was carried out to assess the anti-epileptic effects of aspirin when administered during the chronic stage of temporal lobe epilepsy [TLE] in mice. The alteration of hippocampal neurogenesis was also examined for raising a possible mechanism underlying the protective effect of anti-inflammatory treatment in the TLE. Two months after pilocarpine-induced status epilepticus, the chronically epileptic mice were treated with aspirin (20 mg, 60 mg or 80 mg/kg) once a day for 10 weeks. Spontaneous recurrent seizures were monitored by video camera for 2 weeks. To evaluate the profile of hippocampal neurogenesis, the newly generated cells in the dentate gyrus were labeled by the proliferation marker BrdU. The newborn neurons that extended axons to CA3 area were visualized by cholera toxin B subunit retrograde tracing. Administration of aspirin with a dosage of 60 mg or 80 mg/kg initiated at 2 months after pilocarpine-induced status epilepticus significantly reduced the frequency and duration of spontaneous recurrent seizures. Aspirin treatment also increased the number of newborn neurons with anatomic integration through improving the survival of the newly generated cells. Aspirin treatment during the chronic stage of TLE could attenuate the spontaneous recurrent seizures in mice. Promotion of hippocampal neurogenesis and inhibition of COX-PGE2 pathway might partly contribute to this anti-epileptic effect. Highlights • Aspirin attenuates spontaneous recurrent seizures of chronically epileptic mice • Aspirin increases neurogenesis of chronically epileptic hippocampus by improving the survival of newly generated cells • Promotion of hippocampal neurogenesis and inhibition

  4. Alteration in the endogenous intestinal flora of swiss webster mice by experimental Angiostrongylus costaricensis infection

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    Vandack Nobre

    2004-11-01

    Full Text Available The association between worm infections and bacterial diseases has only recently been emphasized. This study examined the effect of experimental Angiostrongylus costaricensis infection on endogenous intestinal flora of Swiss Webster mice. Eight mice aging six weeks were selected for this experiment. Four were infected with A. costaricensis and the other four were used as controls. Twenty eight days after the worm infection, all mice in both groups were sacrificed and samples of the contents of the ileum and colon were obtained and cultured for aerobic and anaerobic bacteria. In the mice infected with A. costaricensis there was a significant increase in the number of bacteria of the endogenous intestinal flora, accompanied by a decrease in the number of Peptostreptococcus spp. This alteration in the intestinal flora of mice infected by the nematode may help to understand some bacterial infections described in humans.

  5. Airway inflammation in nonobstructive and obstructive chronic bronchitis with chronic haemophilus influenzae airway infection. Comparison with noninfected patients with chronic obstructive pulmonary disease

    NARCIS (Netherlands)

    Bresser, P.; Out, T. A.; van Alphen, L.; Jansen, H. M.; Lutter, R.

    2000-01-01

    Nonencapsulated Haemophilus influenzae often causes chronic infections of the lower respiratory tract in both nonobstructive and obstructive chronic bronchitis. We assessed airway inflammation in clinically stable, chronically H. influenzae-infected patients with nonobstructive (CB-HI, n = 10) and

  6. Respiratory and intraperitoneal infection of mice with encephalomyocarditis cirus

    International Nuclear Information System (INIS)

    Bogaerts, W.J.C.; Durville-van der Oord, B.J.

    1975-01-01

    The relationships governing host resistance to viraliinfection were evaluated in mice following respiratory or peritoneal infection with three strains of encephalomyocarditis virus, which were antigenically similar but differed in virulence. The contribution of non-specific resistance to the overall defense of the host was assessed in mice that had received 450 R of X-radiation prior to viral infection. Survival time correlated with the degree of attenuation of the virus strains and was not influenced by sublethal X-irradiation and route of inoculation, provided that the viral dose was expressed in LD 50 units

  7. Chronic Gastritis and its Association with H. Pylori Infection.

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    Fatema, J; Khan, A H; Uddin, M J; Rahman, M H; Saha, M; Safwath, S A; Alam, M J; Mamun, M A

    2015-10-01

    This cross sectional study was designed to see association of chronic gastritis including its type with H. pylori infection. Consecutive patients undergoing endoscopic examination having histopathological evidence of chronic gastritis were enrolled in the study and was done in Sylhet MAG Osmani Medical College from July 2011 to June 2012. Biopsies were taken from antrum, body and fundus in all patients. Histopathological examinations were done using H-E stain and for detection of H. pylori, rapid urease test, anti-H.pylori antibody test and histopathological test with modified Giemsa stain were done. Patients having results positive in at least two methods were considered infected by H. pylori. Total 80 dyspeptic patients having chronic gastritis were evaluated. Out of them 67(83.8%) had H. pylori infection and 13(16.2%) were H. pylori negative. Among all patients 57(71.2%) had pangastritis and 23(28.8%) had antral gastritis with female and male predominance respectively. H. pylori infection was present in 49(86.0%) cases of pangastritis and 18(78.3%) cases of antral gastritis. H. pylori infection was a little higher among males (34, 50.7%) females (33, 49.3%). H. pylori infection is the predominant cause of chronic gastritis and pangastritis is the major type.

  8. Prion protein protects mice from lethal infection with influenza A viruses.

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    Junji Chida

    2018-05-01

    Full Text Available The cellular prion protein, designated PrPC, is a membrane glycoprotein expressed abundantly in brains and to a lesser extent in other tissues. Conformational conversion of PrPC into the amyloidogenic isoform is a key pathogenic event in prion diseases. However, the physiological functions of PrPC remain largely unknown, particularly in non-neuronal tissues. Here, we show that PrPC is expressed in lung epithelial cells, including alveolar type 1 and 2 cells and bronchiolar Clara cells. Compared with wild-type (WT mice, PrPC-null mice (Prnp0/0 were highly susceptible to influenza A viruses (IAVs, with higher mortality. Infected Prnp0/0 lungs were severely injured, with higher inflammation and higher apoptosis of epithelial cells, and contained higher reactive oxygen species (ROS than control WT lungs. Treatment with a ROS scavenger or an inhibitor of xanthine oxidase (XO, a major ROS-generating enzyme in IAV-infected lungs, rescued Prnp0/0 mice from the lethal infection with IAV. Moreover, Prnp0/0 mice transgenic for PrP with a deletion of the Cu-binding octapeptide repeat (OR region, Tg(PrPΔOR/Prnp0/0 mice, were also highly susceptible to IAV infection. These results indicate that PrPC has a protective role against lethal infection with IAVs through the Cu-binding OR region by reducing ROS in infected lungs. Cu content and the activity of anti-oxidant enzyme Cu/Zn-dependent superoxide dismutase, SOD1, were lower in Prnp0/0 and Tg(PrPΔOR/Prnp0/0 lungs than in WT lungs. It is thus conceivable that PrPC functions to maintain Cu content and regulate SOD1 through the OR region in lungs, thereby reducing ROS in IAV-infected lungs and eventually protecting them from lethal infection with IAVs. Our current results highlight the role of PrPC in protection against IAV infection, and suggest that PrPC might be a novel target molecule for anti-influenza therapeutics.

  9. Extensive immune-mediated hippocampal damage in mice surviving infection with neuroadapted Sindbis virus

    International Nuclear Information System (INIS)

    Kimura, Takashi; Griffin, Diane E.

    2003-01-01

    Viral infections of the central nervous system and immune responses to these infections cause a variety of neurological diseases. Infection of weanling mice with Sindbis virus causes acute nonfatal encephalomyelitis followed by clearance of infectious virus, but persistence of viral RNA. Infection with a neuroadapted strain of Sindbis virus (NSV) causes fatal encephalomyelitis, but passive transfer of immune serum after infection protects from fatal disease and infectious virus is cleared. To determine whether persistent NSV RNA is associated with neurological damage, we examined the brains of recovered mice and found progressive loss of the hippocampal gyrus, adjacent white matter, and deep cerebral cortex associated with mononuclear cell infiltration. Mice deficient in CD4 + T cells showed less tissue loss, while mice lacking CD8 + T cells showed lesions comparable to those in immunocompetent mice. Mice deficient in both CD4 + and CD8 + T cells developed severe tissue loss similar to immunocompetent mice and this was associated with extensive infiltration of macrophages. The number of CD4 + cells and macrophage/microglial cells, but not CD8 + cells, infiltrating the hippocampal gyrus was correlated with the number of terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling positive pyramidal neurons. These results suggest that CD4 + T cells can promote progressive neuronal death and tissue injury, despite clearance of infectious virus

  10. Interferon production and immune response induction in pathogenic rabies virus-infected mice

    Energy Technology Data Exchange (ETDEWEB)

    Marcovistz, R; Leal, E C; De Souza Matos, D C [Departamento de Immunologia, Instituto Oswaldo Cruz, Caixa Postal 926, 21045 Rio de Janeiro (Brazil); Tsiang, H [Service Rage, Istitut Pasteur, Paris (France)

    1994-08-01

    Pathogenic parental rabies virus strain CVS (challenge virus standard) and its apathogenic variant RV194-2 were shown to differ in their ability to induce interferon (IFN) and immune response of the host. After intracerebral inoculation. IFN and antibody production was higher in the RV194-2 virus-infected mice than in the CVS infection. The enhancement of 2-5A synthetase activity, an IFN-mediated enzyme marker, showed biochemical evidence that IFN is active in both apathogenic and pathogenic infections. On the other hand, spontaneous proliferation in vitro of thymocytes and splenocytes from CVS virus-infected mice was strongly inhibited in contrast to the RV194-2 infection. In the CVS infection, the thymocyte proliferation However, in the RV194-2 infection, the thymocyte proliferation was higher than of the splenocytes. These results suggest a better performance of T-cell response to the RV194-2 infection. This fact can be critical for an enhancement of antibody production in the apathogenic infection and subsequent virus clearance from the brain of RV194-2 virus-infected mice. (author) 1 fig., 3 tabs., 32 refs.

  11. Testing in mice the hypothesis that melanin is protective in malaria infections.

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    Michael Waisberg

    Full Text Available Malaria has had the largest impact of any infectious disease on shaping the human genome, exerting enormous selective pressure on genes that improve survival in severe malaria infections. Modern humans originated in Africa and lost skin melanization as they migrated to temperate regions of the globe. Although it is well documented that loss of melanization improved cutaneous Vitamin D synthesis, melanin plays an evolutionary ancient role in insect immunity to malaria and in some instances melanin has been implicated to play an immunoregulatory role in vertebrates. Thus, we tested the hypothesis that melanization may be protective in malaria infections using mouse models. Congenic C57BL/6 mice that differed only in the gene encoding tyrosinase, a key enzyme in the synthesis of melanin, showed no difference in the clinical course of infection by Plasmodium yoelii 17XL, that causes severe anemia, Plasmodium berghei ANKA, that causes severe cerebral malaria or Plasmodium chabaudi AS that causes uncomplicated chronic disease. Moreover, neither genetic deficiencies in vitamin D synthesis nor vitamin D supplementation had an effect on survival in cerebral malaria. Taken together, these results indicate that neither melanin nor vitamin D production improve survival in severe malaria.

  12. Increased anxiety, voluntary alcohol consumption and ethanol-induced place preference in mice following chronic psychosocial stress.

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    Bahi, Amine

    2013-07-01

    Stress exposure is known to be a risk factor for alcohol use and anxiety disorders. Comorbid chronic stress and alcohol dependence may lead to a complicated and potentially severe treatment profile. To gain an understanding of the interaction between chronic psychosocial stress and drug exposure, we studied the effects of concomitant chronic stress exposure on alcohol reward using two-bottle choice and ethanol-conditioned place preference (CPP). The study consisted of exposure of the chronic subordinate colony (CSC) mice "intruders" to an aggressive "resident" mouse for 19 consecutive days. Control mice were single housed (SHC). Ethanol consumption using two-bottle choice paradigm and ethanol CPP acquisition was assessed at the end of this time period. As expected, CSC exposure increased anxiety-like behavior and reduced weight gain as compared to SHC controls. Importantly, in the two-bottle choice procedure, CSC mice showed higher alcohol intake than SHC. When testing their response to ethanol-induced CPP, CSC mice achieved higher preference for the ethanol-paired chamber. In fact, CSC exposure increased ethanol-CPP acquisition. Taken together, these data demonstrate the long-term consequences of chronic psychosocial stress on alcohol intake in male mice, suggesting chronic stress as a risk factor for developing alcohol consumption and/or anxiety disorders.

  13. Trypanosoma Infection Favors Brucella Elimination via IL-12/IFNγ-Dependent Pathways

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    Arnaud Machelart

    2017-07-01

    Full Text Available This study develops an original co-infection model in mice using Brucella melitensis, the most frequent cause of human brucellosis, and Trypanosoma brucei, the agent of African trypanosomiasis. Although the immunosuppressive effects of T. brucei in natural hosts and mice models are well established, we observed that the injection of T. brucei in mice chronically infected with B. melitensis induces a drastic reduction in the number of B. melitensis in the spleen, the main reservoir of the infection. Similar results are obtained with Brucella abortus- and Brucella suis-infected mice and B. melitensis-infected mice co-infected with Trypanosoma cruzi, demonstrating that this phenomenon is not due to antigenic cross-reactivity. Comparison of co-infected wild-type and genetically deficient mice showed that Brucella elimination required functional IL-12p35/IFNγ signaling pathways and the presence of CD4+ T cells. However, the impact of wild type and an attenuated mutant of T. brucei on B. melitensis were similar, suggesting that a chronic intense inflammatory reaction is not required to eliminate B. melitensis. Finally, we also tested the impact of T. brucei infection on the course of Mycobacterium tuberculosis infection. Although T. brucei strongly increases the frequency of IFNγ+CD4+ T cells, it does not ameliorate the control of M. tuberculosis infection, suggesting that it is not controlled by the same effector mechanisms as Brucella. Thus, whereas T. brucei infections are commonly viewed as immunosuppressive and pathogenic, our data suggest that these parasites can specifically affect the immune control of Brucella infection, with benefits for the host.

  14. Extrahepatic manifestations associated with Chronic Hepatitis C Virus Infection

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    A. Flores-Chávez

    Full Text Available Summary Chronic hepatitis C virus (HCV infection has been associated with both organ-specific and systemic autoimmune diseases, with cryoglobulinemia being the most frequent associated disease. Experimental, virologic, and clinical evidence have demon-strated a close association between HCV infection and some systemic autoimmune diseases, especially Sjögren’s syndrome, but also rheumatoid arthritis and lupus. A higher prevalence of hematological processes has also been described in patients with HCV infection, including cytopenias and lymphoproliferative disorders (B-cell lymphoma. In addition, patients with chronic HCV infection have a higher frequency of other extrahepatic manifestations including endocrine, metabolic and cardiovascular disorders that may worse the prognosis of patients, along with neuropsychiatric manifestations and general symptoms that have a significant influence on the quality of life of the patient. Direct-acting antiviral therapies (DAAs that have recently begun to be used are providing the opportunity to effectively cure chronic HCV infection and reduce the burden of both hepatic and extrahepatic complications.

  15. Visual and Motor Deficits in Grown-up Mice with Congenital Zika Virus Infection.

    Science.gov (United States)

    Cui, Liyuan; Zou, Peng; Chen, Er; Yao, Hao; Zheng, Hao; Wang, Qian; Zhu, Jing-Ning; Jiang, Shibo; Lu, Lu; Zhang, Jiayi

    2017-06-01

    Human infants with congenital Zika virus (ZIKV) infection exhibit a range of symptoms including microcephaly, intracranial calcifications, macular atrophy and arthrogryposis. More importantly, prognosis data have lagged far behind the recent outbreak of ZIKV in 2015. In this work, we allow congenitally ZIKV-infected mice to grow into puberty. These mice exhibited motor incoordination and visual dysfunctions, which can be accounted by anatomical defects in the retina and cerebellar cortex. In contrary, anxiety level of the ZIKV-infected mice is normal. The spectrum of anatomical and behavioral deficits is consistent across different mice. Our data provided evidence that may help predict the public health burden in terms of prognosis of ZIKV-related congenital brain malformations in an animal model. Our study provided behavioral evaluation for the prognosis of congenital ZIKV infection and provides a platform for screening and evaluation of drugs candidates and treatment aiming at improving regeneration of infected neurons to prevent sequelae caused by ZIKV infection of fetus. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Efficacy of protocols for induction of chronic hyperthyroidism in male and female mice.

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    Engels, Kathrin; Rakov, Helena; Zwanziger, Denise; Hönes, Georg Sebastian; Rehders, Maren; Brix, Klaudia; Köhrle, Josef; Möller, Lars Christian; Führer, Dagmar

    2016-10-01

    Protocols for induction of hyperthyroidism in mice are highly variable and mostly involve short-term thyroid hormone (TH) treatment. In addition, little is known about a possible influence of sex on experimental TH manipulation. Here we analyzed the efficacy of intraperitoneal vs. oral levothyroxine (T4) administration to induce chronic hyperthyroidism in male and female mice and asked which T4 dosing intervals are required to achieve stable organ thyrotoxicosis. T4 was administered intraperitoneally or orally over a period of 6/7 weeks. Assessment included monitoring of body weight, TH serum concentrations, and serial quantitative TH target gene expression analysis in liver and heart. Our results show that both intraperitoneal and oral T4 treatment are reliable methods for induction of chronic hyperthyroidism in mice. Thereby T4 injection intervals should not exceed 48 h and oral levothyroxine should be administered continuously during experiments and up to sacrifice to ensure a hyperthyroid organ state. Furthermore, we found a sex-dependent variation in levothyroxine-induced TH serum state, with significantly higher T4 concentrations in female mice, while expression of investigated classical TH responsive genes in liver and heart did not vary with animal's sex. In summary, our study shows that common approaches for rendering rodents thyrotoxic can also be used for induction of chronic hyperthyroidism in male and female mice. Thereby T4 dosing intervals are critical as are read-out parameters to verify a chronic thyrotoxic organ state.

  17. Chronic inhibition of dopamine β-hydroxylase facilitates behavioral responses to cocaine in mice.

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    Meriem Gaval-Cruz

    Full Text Available The anti-alcoholism medication, disulfiram (Antabuse, decreases cocaine use in humans regardless of concurrent alcohol consumption and facilitates cocaine sensitization in rats, but the functional targets are unknown. Disulfiram inhibits dopamine β-hydroxylase (DBH, the enzyme that converts dopamine (DA to norepinephrine (NE in noradrenergic neurons. The goal of this study was to test the effects of chronic genetic or pharmacological DBH inhibition on behavioral responses to cocaine using DBH knockout (Dbh -/- mice, disulfiram, and the selective DBH inhibitor, nepicastat. Locomotor activity was measured in control (Dbh +/- and Dbh -/- mice during a 5 day regimen of saline+saline, disulfiram+saline, nepicastat+saline, saline+cocaine, disulfiram+cocaine, or nepicastat+cocaine. After a 10 day withdrawal period, all groups were administered cocaine, and locomotor activity and stereotypy were measured. Drug-naïve Dbh -/- mice were hypersensitive to cocaine-induced locomotion and resembled cocaine-sensitized Dbh +/- mice. Chronic disulfiram administration facilitated cocaine-induced locomotion in some mice and induced stereotypy in others during the development of sensitization, while cocaine-induced stereotypy was evident in all nepicastat-treated mice. Cocaine-induced stereotypy was profoundly increased in the disulfiram+cocaine, nepicastat+cocaine, and nepicastat+saline groups upon cocaine challenge after withdrawal in Dbh +/- mice. Disulfiram or nepicastat treatment had no effect on behavioral responses to cocaine in Dbh -/- mice. These results demonstrate that chronic DBH inhibition facilitates behavioral responses to cocaine, although different methods of inhibition (genetic vs. non-selective inhibitor vs. selective inhibitor enhance qualitatively different cocaine-induced behaviors.

  18. Chronic Inhibition of Dopamine β-Hydroxylase Facilitates Behavioral Responses to Cocaine in Mice

    Science.gov (United States)

    Gaval-Cruz, Meriem; Liles, Larry Cameron; Iuvone, Paul Michael; Weinshenker, David

    2012-01-01

    The anti-alcoholism medication, disulfiram (Antabuse), decreases cocaine use in humans regardless of concurrent alcohol consumption and facilitates cocaine sensitization in rats, but the functional targets are unknown. Disulfiram inhibits dopamine β-hydroxylase (DBH), the enzyme that converts dopamine (DA) to norepinephrine (NE) in noradrenergic neurons. The goal of this study was to test the effects of chronic genetic or pharmacological DBH inhibition on behavioral responses to cocaine using DBH knockout (Dbh −/−) mice, disulfiram, and the selective DBH inhibitor, nepicastat. Locomotor activity was measured in control (Dbh +/−) and Dbh −/− mice during a 5 day regimen of saline+saline, disulfiram+saline, nepicastat+saline, saline+cocaine, disulfiram+cocaine, or nepicastat+cocaine. After a 10 day withdrawal period, all groups were administered cocaine, and locomotor activity and stereotypy were measured. Drug-naïve Dbh −/− mice were hypersensitive to cocaine-induced locomotion and resembled cocaine-sensitized Dbh +/− mice. Chronic disulfiram administration facilitated cocaine-induced locomotion in some mice and induced stereotypy in others during the development of sensitization, while cocaine-induced stereotypy was evident in all nepicastat-treated mice. Cocaine-induced stereotypy was profoundly increased in the disulfiram+cocaine, nepicastat+cocaine, and nepicastat+saline groups upon cocaine challenge after withdrawal in Dbh +/− mice. Disulfiram or nepicastat treatment had no effect on behavioral responses to cocaine in Dbh −/− mice. These results demonstrate that chronic DBH inhibition facilitates behavioral responses to cocaine, although different methods of inhibition (genetic vs. non-selective inhibitor vs. selective inhibitor) enhance qualitatively different cocaine-induced behaviors. PMID:23209785

  19. Chronic psychosocial stress causes delayed extinction and exacerbates reinstatement of ethanol-induced conditioned place preference in mice.

    Science.gov (United States)

    Bahi, Amine; Dreyer, Jean-Luc

    2014-01-01

    We have shown previously, using an animal model of voluntary ethanol intake and ethanol-conditioned place preference (EtOH-CPP), that exposure to chronic psychosocial stress induces increased ethanol intake and EtOH-CPP acquisition in mice. Here, we examined the impact of chronic subordinate colony (CSC) exposure on EtOH-CPP extinction, as well as ethanol-induced reinstatement of CPP. Mice were conditioned with saline or 1.5 g/kg ethanol and were tested in the EtOH-CPP model. In the first experiment, the mice were subjected to 19 days of chronic stress, and EtOH-CPP extinction was assessed during seven daily trials without ethanol injection. In the second experiment and after the EtOH-CPP test, the mice were subjected to 7 days of extinction trials before the 19 days of chronic stress. Drug-induced EtOH-CPP reinstatement was induced by a priming injection of 0.5 g/kg ethanol. Compared to the single-housed colony mice, CSC mice exhibited increased anxiety-like behavior in the elevated plus maze (EPM) and the open field tests. Interestingly, the CSC mice showed delayed EtOH-CPP extinction. More importantly, CSC mice showed increased alcohol-induced reinstatement of the EtOH-CPP behavior. Taken together, this study indicates that chronic psychosocial stress can have long-term effects on EtOH-CPP extinction as well as drug-induced reinstatement behavior and may provide a suitable model to study the latent effects of chronic psychosocial stress on extinction and relapse to drug abuse.

  20. Chronic hepatitis caused by persistent parvovirus B19 infection

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    Mogensen Trine H

    2010-08-01

    Full Text Available Abstract Background Human infection with parvovirus B19 may lead to a diverse spectrum of clinical manifestations, including benign erythema infectiosum in children, transient aplastic crisis in patients with haemolytic anaemia, and congenital hydrops foetalis. These different diseases represent direct consequences of the ability of parvovirus B19 to target the erythroid cell lineage. However, accumulating evidence suggests that this virus can also infect other cell types resulting in diverse clinical manifestations, of which the pathogenesis remains to be fully elucidated. This has prompted important questions regarding the tropism of the virus and its possible involvement in a broad range of infectious and autoimmune medical conditions. Case Presentation Here, we present an unusual case of persistent parvovirus B19 infection as a cause of chronic hepatitis. This patient had persistent parvovirus B19 viraemia over a period of more than four years and displayed signs of chronic hepatitis evidenced by fluctuating elevated levels of ALAT and a liver biopsy demonstrating chronic hepatitis. Other known causes of hepatitis and liver damage were excluded. In addition, the patient was evaluated for immunodeficiency, since she had lymphopenia both prior to and following clearance of parvovirus B19 infection. Conclusions In this case report, we describe the current knowledge on the natural history and pathogenesis of parvovirus B19 infection, and discuss the existing evidence of parvovirus B19 as a cause of acute and chronic hepatitis. We suggest that parvovirus B19 was the direct cause of this patient's chronic hepatitis, and that she had an idiopathic lymphopenia, which may have predisposed her to persistent infection, rather than bone marrow depression secondary to infection. In addition, we propose that her liver involvement may have represented a viral reservoir. Finally, we suggest that clinicians should be aware of parvovirus B19 as an unusual

  1. Epigallocatechin gallate ameliorates chronic fatigue syndrome in mice: behavioral and biochemical evidence.

    Science.gov (United States)

    Sachdeva, Anand Kamal; Kuhad, Anurag; Tiwari, Vinod; Chopra, Kanwaljit

    2009-12-28

    Three decades after the coining of the term chronic fatigue syndrome, the diagnosis of this illness is still symptom based and the aetiology remains elusive. Chronic fatigue syndrome pathogenesis seems to be multifactorial and the possible involvement of immune system is supported. The present study was designed to evaluate the effects of the epigallocatechin gallate in a mouse model of immunologically induced chronic fatigue. On 19th day, after lipopolysaccharide/Brucella abortus administration, the mice showed significant increase in immobility period, post swim fatigue and thermal hyperalgesia. Behavioral deficits were coupled with enhanced oxidative-nitrosative stress as evident by increased lipid peroxidation, nitrite levels and decreased endogenous antioxidant enzymes (superoxide dismutase, reduced glutathione and catalase) and inflammation (increased levels of tumor necrosis factor-alpha and tissue growth factor-beta). Chronic treatment with epigallocatechin gallate restored these behavioral and biochemical alterations in mice. The present study points out towards the beneficial effect of epigallocatechin gallate in the amelioration of chronic fatigue syndrome and thus may provide a new, effective and powerful strategy to treat chronic fatigue syndrome.

  2. Protection of mice against Giardia muris infection.

    Science.gov (United States)

    Roberts-Thomson, I C; Mitchell, G F

    1979-01-01

    Strains of mice showing relatively rapid (BALB/c) and defective (C3H/He) spontaneous elimination of Giardia muris displayed marked differences in the degree of resistance to infection induced by prior injection of trophozoites in Freund complete adjuvant. PMID:468385

  3. Cost of Illness of Chronic Hepatitis B Infection in Vietnam

    NARCIS (Netherlands)

    Tu, Hong Anh T.; Woerdenbag, Herman J.; Riewpaiboon, Arthorn; Kane, Sumit; Le, Diep M.; Postma, Maarten J.; Li, Shu Chuen

    2012-01-01

    To estimate the total financial burden of chronic hepatitis B virus (HBV) infection for Vietnam by quantifying the direct medical, the direct nonmedical, and indirect costs among patients with various stages of chronic HBV infection. Direct medical cost data were retrieved retrospectively from

  4. Mice with ablated adult brain neurogenesis are not impaired in antidepressant response to chronic fluoxetine.

    Science.gov (United States)

    Jedynak, Paulina; Kos, Tomasz; Sandi, Carmen; Kaczmarek, Leszek; Filipkowski, Robert K

    2014-09-01

    The neurogenesis hypothesis of major depression has two main facets. One states that the illness results from decreased neurogenesis while the other claims that the very functioning of antidepressants depends on increased neurogenesis. In order to verify the latter, we have used cyclin D2 knockout mice (cD2 KO mice), known to have virtually no adult brain neurogenesis, and we demonstrate that these mice successfully respond to chronic fluoxetine. After unpredictable chronic mild stress, mutant mice showed depression-like behavior in forced swim test, which was eliminated with chronic fluoxetine treatment, despite its lack of impact on adult hippocampal neurogenesis in cD2 KO mice. Our results suggest that new neurons are not indispensable for the action of antidepressants such as fluoxetine. Using forced swim test and tail suspension test, we also did not observe depression-like behavior in control cD2 KO mice, which argues against the link between decreased adult brain neurogenesis and major depression. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Interleukin-18 protects mice from Enterovirus 71 infection.

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    Li, Zheng; Wang, Hongbin; Chen, Yihui; Niu, Junling; Guo, Qiuhong; Leng, Qibin; Huang, Zhong; Deng, Zhirui; Meng, Guangxun

    2017-08-01

    Previous study has demonstrated that the NLRP3 inflammasome is essential for protecting murine host against Enterovirus 71 (EV71) infection. However, the underlying mechanism remained unknown. Here we discovered that the pleiotropic cytokine interleukin-18 (IL-18), an NLRP3 inflammasome-dependent effector protein, exhibits a protective capability against EV71 challenge. Deficiency of IL-18 in mice exacerbated EV71 infection, which was reflected by increased viral replication, elevated production of interferons (IFN-β, IFN-γ), proinflammatory cytokines (TNF-α, IL-6) and chemokine CCL2,as well as decreased survival of experimental animals. Conversely, administration of recombinant IL-18 considerably restrained EV71 infection in IL-18 deficient mice. Thus, our results revealed a protective role for IL-18 against EV71 challenge, and indicated a novel therapeutic application for IL-18 in EV71 associated hand, foot, and mouth disease (HFMD). Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Dual role of Fcγ receptors in host defense and disease in Borrelia burgdorferi-infected mice

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    Alexia Anne Belperron

    2014-06-01

    Full Text Available Arthritis in mice infected with the Lyme disease spirochete, Borrelia burgdorferi, results from the influx of innate immune cells responding to the pathogen in the joint and is influenced in part by mouse genetics. Production of inflammatory cytokines by innate immune cells in vitro is largely mediated by Toll-like receptor (TLR interaction with Borrelia lipoproteins, yet surprisingly mice deficient in TLR2 or the TLR signaling molecule MyD88 still develop arthritis comparable to that seen in wild type mice after B. burgdorferi infection. These findings suggest that other, MyD88-independent inflammatory pathways can contribute to arthritis expression. Clearance of B. burgdorferi is dependent on the production of specific antibody and phagocytosis of the organism. As Fc receptors (FcγR are important for IgG-mediated clearance of immune complexes and opsonized particles by phagocytes, we examined the role that FcγR play in host defense and disease in B. burgdorferi-infected mice. B. burgdorferi-infected mice deficient in the Fc receptor common gamma chain (FcεRγ-/- mice harbored ~10 fold more spirochetes than similarly infected wild type mice, and this was associated with a transient increase in arthritis severity. While the elevated pathogen burdens seen in B. burgdorferi-infected MyD88-/- mice were not affected by concomitant deficiency in FcγR, arthritis was reduced in FcεRγ-/-MyD88-/- mice in comparison to wild type or single knockout mice. Gene expression analysis from infected joints demonstrated that absence of both MyD88 and FcγR lowers mRNA levels of proteins involved in inflammation, including Cxcl1 (KC, Xcr1 (Gpr5, IL-1beta, and C reactive protein. Taken together, our results demonstrate a role for FcγR-mediated immunity in limiting pathogen burden and arthritis in mice during the acute phase of B. burgdorferi infection, and further suggest that this pathway contributes to the arthritis that develops in B. burgdorferi-infected

  7. Ultra-low dose of Mycobacterium tuberculosis aerosol creates partial infection in mice.

    Science.gov (United States)

    Saini, Divey; Hopkins, Gregory W; Seay, Sarah A; Chen, Ching-Ju; Perley, Casey C; Click, Eva M; Frothingham, Richard

    2012-03-01

    A murine low dose (LD) aerosol model is commonly used to test tuberculosis vaccines. Doses of 50-400 CFU (24h lung CFU) infect 100% of exposed mice. The LD model measures progression from infection to disease based on organ CFU at defined time points. To mimic natural exposure, we exposed mice to an ultra-low dose (ULD) aerosol. We estimated the presented dose by sampling the aerosol. Female C57BL/6 mice were exposed to Mycobacterium tuberculosis H37Rv aerosol at 1.0, 1.1, 1.6, 5.4, and 11 CFU presented dose, infecting 27%, 36%, 36%, 100%, and 95% of mice, respectively. These data are compatible with a stochastic infection event (Poisson distribution, weighted R(2)=0.97) or with a dose-response relationship (sigmoid distribution, weighted R(2)=0.97). Based on the later assumption, the ID50 was 1.6CFU presented dose (95% confidence interval, 1.2-2.1). We compared organ CFU after ULD and LD aerosols (5.4 vs. 395CFU presented dose). Lung burden was 30-fold lower in the ULD model at 4 weeks (3.4 vs. 4.8 logs, pLD aerosols had greater within-group CFU variability. Exposure to ULD aerosols leads to infection in a subset of mice, and to persistently low organ CFU. The ULD aerosol model may resemble human pulmonary tuberculosis more closely than the standard LD model, and may be used to identify host or bacterial factors that modulate the initial infection event. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Axl is not an indispensable factor for Zika virus infection in mice.

    Science.gov (United States)

    Wang, Zhao-Yang; Wang, Zai; Zhen, Zi-Da; Feng, Kai-Hao; Guo, Jing; Gao, Na; Fan, Dong-Ying; Han, Dai-Shu; Wang, Pei-Gang; An, Jing

    2017-08-01

    Recently, Zika virus (ZIKV) outbreak has been associated with a sharp increase in cases of Guillain-Barré syndrome and severe fetal abnormalities. However, the mechanism underlying the interaction of ZIKV with host cells is not yet clear. Axl, a receptor tyrosine kinase, is postulated as a receptor for ZIKV entry; however, its in vivo role during ZIKV infection and its impact on the outcome of the disease have not been fully characterized and evaluated. Moreover, there are contradictory results on its involvement in ZIKV infection. Here we utilized Axl-deficient mice (Axl-/-) and their littermates (Axl+/-) to study the in vivo role of Axl in ZIKV infection. Our results showed that both Axl+/- and Axl-/- suckling mice supported the replication of ZIKV and presented clinical manifestations. No significant difference has been found between Axl-deficient mice and their littermates in terms of the survival rate, clinical manifestations, viral load, ZIKV distribution and histopathological changes in major organs. These results therefore indicate that Axl is not an indispensable factor for ZIKV infection in mice.

  9. Naïve B cells reduce fungal dissemination in Cryptococcus neoformans infected Rag1-/- mice.

    Science.gov (United States)

    Dufaud, Chad; Rivera, Johanna; Rohatgi, Soma; Pirofski, Liise-Anne

    2018-01-01

    IgM and B-1 cell deficient mice exhibit early C. neoformans dissemination from lungs to brain, but a definitive role for B cells in conferring resistance to C. neoformans dissemination has not been established. To address this question, we developed an intranasal (i.n.) C. neoformans infection model in B and T cell deficient Rag1 -/- mice and found they also exhibit earlier fungal dissemination and higher brain CFU than wild-type C57Bl/6 (wild-type) mice. To probe the effect of B cells on fungal dissemination, Rag1 -/- mice were given splenic (intravenously) or peritoneal (intraperitoneally) B cells from wild-type mice and infected i.n. with C. neoformans 7 d later. Mice that received B cells had lung histopathology resembling wild type mice 14 d post-infection, and B-1, not B-2 or T cells in their lungs, and serum and lung IgM and IgG 21 d post-infection. Lung CFU were comparable in wild-type, Rag1 -/-, and Rag1 -/- mice that received B cells 21 d post-infection, but brain CFU were significantly lower in mice that received B cells than Rag1 -/- mice that did not. To determine if natural antibody can promote immunity in our model, we measured alveolar macrophage phagocytosis of C. neoformans in Rag1 -/- mice treated with naive wild-type IgM-sufficient or sIgM -/- IgM-deficient sera before infection. Compared to IgM-deficient sera, IgM-sufficient sera significantly increased phagocytosis. Our data establish B cells are able to reduce early C. neoformans dissemination in mice and suggest natural IgM may be a key mediator of early antifungal immunity in the lungs.

  10. Chronic social isolation and chronic variable stress during early development induce later elevated ethanol intake in adult C57BL/6J mice.

    Science.gov (United States)

    Lopez, Marcelo F; Doremus-Fitzwater, Tamara L; Becker, Howard C

    2011-06-01

    Experience with stress situations during early development can have long-lasting effects on stress- and anxiety-related behaviors. Importantly, this can also favor drug self-administration. These studies examined the effects of chronic social isolation and/or variable stress experiences during early development on subsequent voluntary ethanol intake in adult male and female C57BL/6J mice. The experiments were conducted to evaluate the effect of chronic isolation between weaning and adulthood (Experiment 1), chronic isolation during adulthood (Experiment 2), and chronic variable stress (CVS) alone or in combination with chronic social isolation between weaning and adulthood (Experiment 3) on subsequent voluntary ethanol intake. Mice were born in our facility and were separated into two housing conditions: isolate housed (one mouse/cage) or group housed (four mice/cage) according to sex. Separate groups were isolated for 40 days starting either at time of weaning postnatal day 21 (PD 21) (early isolation, Experiments 1 and 3) or at adulthood (PD 60: late isolation, Experiment 2). The effects of housing condition on subsequent ethanol intake were assessed starting at around PD 65 in Experiments 1 and 3 or PD 105 days in Experiment 2. In Experiment 3, starting at PD 32, isolate-housed and group-housed mice were either subjected to CVS or left undisturbed. CVS groups experienced random presentations of mild stressors for 14 days, including exposure to an unfamiliar open field, restraint, physical shaking, and forced swim, among others. All mice were tested for ethanol intake for 14 days using a two-bottle choice (ethanol 15% vol/vol vs. water) for a 2-h limited access procedure. Early social isolation resulted in greater ethanol intake compared with the corresponding group-housed mice (Experiment 1). In contrast, social isolation during adulthood (late isolation) did not increase subsequent ethanol intake compared with the corresponding group-housed mice (Experiment 2

  11. Experimental infection of Balb/c nude mice with Hepatitis E virus

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    Zhu Jianguo

    2009-06-01

    Full Text Available Abstract Background Several animal species can reportedly act as reservoirs for Hepatitis E virus (HEV, a zoonotic pathogen. HEV and antibody to the virus have been detected in a variety of animals including rodents. Pig and rat models for HEV have been established for HEV, but a nude mouse has not yet been developed. Methods Balb/c nude mice were inoculated with swine HEV, both orally and via intravenous injection to insure infection. Negative control and experimental contact-exposed groups of mice were also included in the study. The liver, spleen, kidney, jejunum, ileum, cecum and colon of each mouse from all three groups were collected for reverse transcription nested polymerase chain reaction (RT-nPCR detection, indirect immunofluorescence observation and histopathologic examination. The sera from nude mice were tested for anti-HEV IgG by enzyme linked immunosorbent assay (ELISA. Activities of liver enzymes, including alanine aminotransferase (ALT, aspartate aminotransferase (AST and alkaline phosphatase (ALP, as well as total bilirubin (TBIL were also measured in the sera of the nude mice. Results HEV antigens and HEV RNA were detected in liver, spleen, kidney, jejunum, ileum and colon both by indirect immunofluorescence and by RT-nPCR in all of the inoculated and in one of the contact-exposed nude mice. Histopathological changes were observed in the liver and spleen of these mice. Infected mice showed increased levels of AST, ALP, and anti-HEV IgG in sera. The livers of contact-exposed mice showed obvious histopathological damage. Conclusion Nude mice could be readily infected by HEV isolated from pigs. The nude mouse may therefore be a useful animal model for studying the pathogenesis of HEV.

  12. Tears from children with chronic hepatitis B virus (HBV) infection are infectious vehicles of HBV transmission: experimental transmission of HBV by tears, using mice with chimeric human livers.

    Science.gov (United States)

    Komatsu, Haruki; Inui, Ayano; Sogo, Tsuyoshi; Tateno, Akihiko; Shimokawa, Reiko; Fujisawa, Tomoo

    2012-08-15

    Body fluids such as saliva, urine, sweat, and tears from hepatitis B virus (HBV) carriers are potential sources of HBV transmission. Thirty-nine children and 8 adults who were chronically infected with HBV were enrolled. Real-time polymerase chain reaction was used for the quantification of HBV DNA. HBV DNA was detected in 73.7% of urine samples (14 of 19), 86.8% of saliva samples (33 of 38), 100% of tear samples (11 of 11), and 100% of sweat samples (9 of 9). Mean HBV DNA levels (±SD) in urine, saliva, tears, and sweat were 4.3 ± 1.1 log copies/mL, 5.9 ± 1.2 log copies/mL, 6.2 ± 0.7 log copies/mL, and 5.2 ± 0.6 log copies/mL, respectively. A statistically significant correlation was observed between the HBV DNA level in serum specimens and HBV DNA levels in saliva and tear specimens (r = 0.88; P Tear specimens from a child were injected intravenously into 2 human hepatocyte-transplanted chimeric mice. One week after inoculation, both chimeric mice had serum positive for HBV DNA. The levels of HBV DNA in tear specimens from young children were high. Tears were confirmed to be infectious, using chimeric mice. Strict precautions should be taken against direct contact with body fluids from HBV carriers with high-level viremia.

  13. Ag85-focused T-cell immune response controls Mycobacterium avium chronic infection.

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    Bruno Cerqueira-Rodrigues

    Full Text Available CD4+ T cells are essential players for the control of mycobacterial infections. Several mycobacterial antigens have been identified for eliciting a relevant CD4+ T cell mediated-immune response, and numerous studies explored this issue in the context of Mycobacterium tuberculosis infection. Antigen 85 (Ag85, a highly conserved protein across Mycobacterium species, is secreted at the early phase of M. tuberculosis infection leading to the proliferation of Ag85-specific CD4+ T cells. However, in the context of Mycobacterium avium infection, little is known about the expression of this antigen and the elicited immune response. In the current work, we investigated if a T cell receptor (TCR repertoire mostly, but not exclusively, directed at Ag85 is sufficient to mount a protective immune response against M. avium. We show that P25 mice, whose majority of T cells express a transgenic TCR specific for Ag85, control M. avium infection at the same level as wild type (WT mice up to 20 weeks post-infection (wpi. During M. avium infection, Ag85 antigen is easily detected in the liver of 20 wpi mice by immunohistochemistry. In spite of the propensity of P25 CD4+ T cells to produce higher amounts of interferon-gamma (IFNγ upon ex vivo stimulation, no differences in serum IFNγ levels are detected in P25 compared to WT mice, nor enhanced immunopathology is detected in P25 mice. These results indicate that a T cell response dominated by Ag85-specific T cells is appropriate to control M. avium infection with no signs of immunopathology.

  14. Early immune response in susceptible and resistant mice strains with chronic Pseudomonas aeruginosa lung infection determines the type of T-helper cell response

    DEFF Research Database (Denmark)

    Moser, C; Hougen, H P; Song, Z

    1999-01-01

    Most cystic fibrosis (CF) patients become chronically infected with Pseudomonas aeruginosa in the lungs. The infection is characterized by a pronounced antibody response and a persistant inflammation dominated by polymorphonuclear neutrophils. Moreover a high antibody response correlates with a p...

  15. Mycobacterium tuberculosis Universal Stress Protein Rv2623 Regulates Bacillary Growth by ATP Binding: Requirement for Establishing Chronic Persistent Infection

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    Drumm, J.; Mi, K; Bilder, P; Sun, M; Lim, J; Bielefeldt-Ohmann, H; Basaraba, R; So, M; Zhu, G; et. al.

    2009-01-01

    Tuberculous latency and reactivation play a significant role in the pathogenesis of tuberculosis, yet the mechanisms that regulate these processes remain unclear. The Mycobacterium tuberculosisuniversal stress protein (USP) homolog, rv2623, is among the most highly induced genes when the tubercle bacillus is subjected to hypoxia and nitrosative stress, conditions thought to promote latency. Induction of rv2623 also occurs when M. tuberculosis encounters conditions associated with growth arrest, such as the intracellular milieu of macrophages and in the lungs of mice with chronic tuberculosis. Therefore, we tested the hypothesis that Rv2623 regulates tuberculosis latency. We observed that an Rv2623-deficient mutant fails to establish chronic tuberculous infection in guinea pigs and mice, exhibiting a hypervirulence phenotype associated with increased bacterial burden and mortality. Consistent with this in vivo growth-regulatory role, constitutive overexpression of rv2623 attenuates mycobacterial growth in vitro. Biochemical analysis of purified Rv2623 suggested that this mycobacterial USP binds ATP, and the 2.9-A-resolution crystal structure revealed that Rv2623 engages ATP in a novel nucleotide-binding pocket. Structure-guided mutagenesis yielded Rv2623 mutants with reduced ATP-binding capacity. Analysis of mycobacteria overexpressing these mutants revealed that the in vitro growth-inhibitory property of Rv2623 correlates with its ability to bind ATP. Together, the results indicate that i M. tuberculosis Rv2623 regulates mycobacterial growth in vitro and in vivo, and ii Rv2623 is required for the entry of the tubercle bacillus into the chronic phase of infection in the host; in addition, iii Rv2623 binds ATP; and iv the growth-regulatory attribute of this USP is dependent on its ATP-binding activity. We propose that Rv2623 may function as an ATP-dependent signaling intermediate in a pathway that promotes persistent infection.

  16. A DNA Vaccine Protects Human Immune Cells against Zika Virus Infection in Humanized Mice

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    Guohua Yi

    2017-11-01

    Full Text Available A DNA vaccine encoding prM and E protein has been shown to induce protection against Zika virus (ZIKV infection in mice and monkeys. However, its effectiveness in humans remains undefined. Moreover, identification of which immune cell types are specifically infected in humans is unclear. We show that human myeloid cells and B cells are primary targets of ZIKV in humanized mice. We also show that a DNA vaccine encoding full length prM and E protein protects humanized mice from ZIKV infection. Following administration of the DNA vaccine, humanized DRAG mice developed antibodies targeting ZIKV as measured by ELISA and neutralization assays. Moreover, following ZIKV challenge, vaccinated animals presented virtually no detectable virus in human cells and in serum, whereas unvaccinated animals displayed robust infection, as measured by qRT-PCR. Our results utilizing humanized mice show potential efficacy for a targeted DNA vaccine against ZIKV in humans.

  17. Inhibition of Cyclooxygenase-2 Prevents Chronic and Recurrent Cystitis

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    Thomas J. Hannan

    2014-11-01

    Full Text Available The spread of multidrug-resistant microorganisms globally has created an urgent need for novel therapeutic strategies to combat urinary tract infections (UTIs. Immunomodulatory therapy may provide benefit, as treatment of mice with dexamethasone during acute UTI improved outcome by reducing the development of chronic cystitis, which predisposes to recurrent infection. Here we discovered soluble biomarkers engaged in myeloid cell development and chemotaxis that were predictive of future UTI recurrence when elevated in the sera of young women with UTI. Translation of these findings revealed that temperance of the neutrophil response early during UTI, and specifically disruption of bladder epithelial transmigration of neutrophils by inhibition of cyclooxygenase-2, protected mice against chronic and recurrent cystitis. Further, proteomics identified bladder epithelial remodeling consequent to chronic infection that enhances sensitivity to neutrophil damage. Thus, cyclooxygenase-2 expression during acute UTI is a critical molecular trigger determining disease outcome and drugs targeting cyclooxygenase-2 could prevent recurrent UTI.

  18. Intra-uterine experimental infection by Ureaplasma diversum induces TNF-α mediated womb inflammation in mice

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    Jamile R. Silva

    2016-01-01

    Full Text Available Ureaplasma diversum is an opportunistic pathogen associated with uterine inflammation, impaired embryo implantation, infertility, abortions, premature birth of calves and neonatal pneumonia in cattle. It has been suggested that the intra-uterine infection by Ureaplasma diversum can cause vascular changes that hinder the success of pregnancy. Thus, the aim of this study was to evaluate the changes of intrauterine site of A/J mice in estrus or proestrus phase inoculated with Ureaplasma diversum. The infection was monitored at 24, 48 and 72 hours by the PCR methodology to detect the Ureaplasma in the inoculation site and the profile of circulating blood cells. Morphological changes, intensity of inflammation and the production of cytokines were compared. The infected mice showed local inflammation through the production of IFN-γ and TNF-α. Ureaplasma diversum infections in the reproductive tract of studied mice seemed to be associated with the production of pro-inflammatory cytokines in uterine parenchyma. The levels of TNF-α of infected mice were dependent on the bacterial load of inoculated Ureaplasma. Uterine experimental infections by Ureaplasma diversum have not been mentioned yet and herein we presented the first report of an intrauterine infection model in mice.

  19. Intra-uterine experimental infection by Ureaplasma diversum induces TNF-α mediated womb inflammation in mice.

    Science.gov (United States)

    Silva, Jamile R; Ferreira, Lício F A A; Oliveira, Percíllia V S; Nunes, Ivanéia V; Pereira, Ítalo S; Timenetsky, Jorge; Marques, Lucas M; Figueiredo, Tiana B; Silva, Robson A A

    2016-01-01

    Ureaplasma diversum is an opportunistic pathogen associated with uterine inflammation, impaired embryo implantation, infertility, abortions, premature birth of calves and neonatal pneumonia in cattle. It has been suggested that the intra-uterine infection by Ureaplasma diversum can cause vascular changes that hinder the success of pregnancy. Thus, the aim of this study was to evaluate the changes of intrauterine site of A/J mice in estrus or proestrus phase inoculated with Ureaplasma diversum. The infection was monitored at 24, 48 and 72 hours by the PCR methodology to detect the Ureaplasma in the inoculation site and the profile of circulating blood cells. Morphological changes, intensity of inflammation and the production of cytokines were compared. The infected mice showed local inflammation through the production of IFN-γ and TNF-α. Ureaplasma diversum infections in the reproductive tract of studied mice seemed to be associated with the production of pro-inflammatory cytokines in uterine parenchyma. The levels of TNF-α of infected mice were dependent on the bacterial load of inoculated Ureaplasma. Uterine experimental infections by Ureaplasma diversum have not been mentioned yet and herein we presented the first report of an intrauterine infection model in mice.

  20. Chronic hepatitis B virus infection in Asian countries.

    Science.gov (United States)

    Merican, I; Guan, R; Amarapuka, D; Alexander, M J; Chutaputti, A; Chien, R N; Hasnian, S S; Leung, N; Lesmana, L; Phiet, P H; Sjalfoellah Noer, H M; Sollano, J; Sun, H S; Xu, D Z

    2000-12-01

    Of the estimated 50 million new cases of hepatitis B virus (HBV) infection diagnosed annually, 5-10% of adults and up to 90% of infants will become chronically infected, 75% of these in Asia where hepatitis B is the leading cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC). In Indonesia, 4.6% of the population was positive for HBsAg in 1994 and of these, 21% were positive for HBeAg and 73% for anti-HBe; 44% and 45% of Indonesian patients with cirrhosis and HCC, respectively, were HBsAg positive. In the Philippines, there appear to be two types of age-specific HBsAg prevalence, suggesting different modes of transmission. In Thailand, 8-10% of males and 6-8% of females are HBsAg positive, with HBsAg also found in 30% of patients with cirrhosis and 50-75% of those with HCC. In Taiwan, 75-80% of patients with chronic liver disease are HBsAg positive, and HBsAg is found in 34% and 72% of patients with cirrhosis and HCC, respectively. In China, 73% of patients with chronic hepatitis and 78% and 71% of those with cirrhosis and HCC, respectively, are HBsAg positive. In Singapore, the prevalence of HBsAg has dropped since the introduction of HBV vaccination and the HBsAg seroprevalence of unvaccinated individuals over 5 years of age is 4.5%. In Malaysia, 5.24% of healthy volunteers, with a mean age of 34 years, were positive for HBsAg in 1997. In the highly endemic countries in Asia, the majority of infections are contracted postnatally or perinatally. Three phases of chronic HBV infection are recognized: phase 1 patients are HBeAg positive with high levels of virus in the serum and minimal hepatic inflammation; phase 2 patients have intermittent or continuous hepatitis of varying degrees of severity; phase 3 is the inactive phase during which viral concentrations are low and there is minimal inflammatory activity in the liver. In general, patients who clear HBeAg have a better prognosis than patients who remain HBeAg-positive for prolonged periods of

  1. Phage inhibit pathogen dissemination by targeting bacterial migrants in a chronic infection model

    DEFF Research Database (Denmark)

    Darch, Sophie E.; Kragh, Kasper N.; Abbott, Evelyn A.

    2017-01-01

    The microbial communities inhabiting chronic infections are often composed of spatially organized micrometer-sized, highly dense aggregates. It has recently been hypothesized that aggregates are responsible for the high tolerance of chronic infections to host immune functions and antimicrobial...... production; however, seeding of new aggregates by dispersed migrants was inhibited. We propose a model in which aggregates provide a mechanism that allows P. aeruginosa to tolerate phage therapy during chronic infection without the need for genetic mutation. IMPORTANCE Bacteria in chronic infections often...... reside in communities composed of micrometer-sized, highly dense aggregates. A primary challenge for studying aggregates has been the lack of laboratory systems that promote natural aggregate formation in relevant environments. Here, we developed a growth medium that mimics chronic lung infection...

  2. The role of fluoxetine on macrophage function in chronic pain (Experimental study in Balb/c mice

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    Dwi Pudjonarko

    2015-11-01

    Full Text Available Chronic pain raises stress conditions such as depression that can lower the cellular immunity. Fluoxetine is an antidepressant  used as an adjuvant in pain management but no one has been linked it with the body immune system. The objectives of this research were to proof the benefits of fluoxetine in  preventing degradation of macrophage function in chronic pain by measuring the macrophage phagocytic index , macrophage NO levels and the liver bacterial count in BALB/c mice infected with Listeria Monocytogenes.A Post Test - Only Control Group Design was conducted using 28 male mice strain BALB /c, age 8-10 weeks. The control group (C, mice got the same standard feed as the other groups. Chronic pain group (P, mice were injected with 20μL intraplantar CFA on day-1. Pain + fluoxetine early group (PFE were treated with P + fluoxetine 5 mg / kg ip day-1, the 4th, the 7th and the 10th, while the Pain + fluoxetine late group (PFL were treated with P + fluoxetine 5 mg / kg ip on day 7th and 10th. All mice were injected with 104 live Listeria monocytogenes iv on day 8th. Termination was performed on day 13th. Differences within groups  were analyzed using  One-way ANOVA and Kruskall Wallis, whereas the correlation of variables were analyzed using  Pearson's product moment. The experimental results showed that The macrophage phagocytic index and NO macrophage level (pg/mL in PFE group(2,24±1,013; 0,24±0,239 was higher than than P group (1,68±0,920; 0,21±0,263 and there was no different in the macrophage phagocytic index of PFE group compared to C group (p=0,583; p=0,805. In PFL group (4,32±1,459; 0,54±0,294 the macrophage phagocytic index as well as NO macrophage level (pg/mL was higher than P group (1,68±0,920; 0,21±0,263 with p=0,002; p=0,017. P group Bacterial count (log cfu/gram (2,30±0,849 was significantly higher than C group(1,15±0,223 (p=0,007, while PFE group bacterial count (1,96±0,653 and PFL group bacterial count (1,84±0

  3. Amide side chain amphiphilic polymers disrupt surface established bacterial bio-films and protect mice from chronic Acinetobacter baumannii infection.

    Science.gov (United States)

    Uppu, Divakara S S M; Samaddar, Sandip; Ghosh, Chandradhish; Paramanandham, Krishnamoorthy; Shome, Bibek R; Haldar, Jayanta

    2016-01-01

    Bacterial biofilms represent the root-cause of chronic or persistent infections in humans. Gram-negative bacterial infections due to nosocomial and opportunistic pathogens such as Acinetobacter baumannii are more difficult to treat because of their inherent and rapidly acquiring resistance to antibiotics. Due to biofilm formation, A. baumannii has been noted for its apparent ability to survive on artificial surfaces for an extended period of time, therefore allowing it to persist in the hospital environment. Here we report, maleic anhydride based novel cationic polymers appended with amide side chains that disrupt surface established multi-drug resistant A. baumannii biofilms. More importantly, these polymers significantly (p polymers also show potent antibacterial efficacy against methicillin resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococci (VRE) and multi-drug resistant clinical isolates of A. baumannii with minimal toxicity to mammalian cells. We observe that optimal hydrophobicity dependent on the side chain chemical structure of these polymers dictate the selective toxicity to bacteria. Polymers interact with the bacterial cell membranes by causing membrane depolarization, permeabilization and energy depletion. Bacteria develop rapid resistance to erythromycin and colistin whereas no detectable development of resistance occurs against these polymers even after several passages. These results suggest the potential use of these polymeric biomaterials in disinfecting biomedical device surfaces after the infection has become established and also for the topical treatment of chronic bacterial infections. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Zika virus infection in immunocompetent pregnant mice causes fetal damage and placental pathology in the absence of fetal infection

    Science.gov (United States)

    Kummer, Lawrence W.; Lanthier, Paula; Kim, In-Jeong; Kuki, Atsuo; Thomas, Stephen J.

    2018-01-01

    Zika virus (ZIKV) infection during human pregnancy may cause diverse and serious congenital defects in the developing fetus. Previous efforts to generate animal models of human ZIKV infection and clinical symptoms often involved manipulating mice to impair their Type I interferon (IFN) signaling, thereby allowing enhanced infection and vertical transmission of virus to the embryo. Here, we show that even pregnant mice competent to generate Type I IFN responses that can limit ZIKV infection nonetheless develop profound placental pathology and high frequency of fetal demise. We consistently found that maternal ZIKV exposure led to placental pathology and that ZIKV RNA levels measured in maternal, placental or embryonic tissues were not predictive of the pathological effects seen in the embryos. Placental pathology included trophoblast hyperplasia in the labyrinth, trophoblast giant cell necrosis in the junctional zone, and loss of embryonic vessels. Our findings suggest that, in this context of limited infection, placental pathology rather than embryonic/fetal viral infection may be a stronger contributor to adverse pregnancy outcomes in mice. Our finding demonstrates that in immunocompetent mice, direct viral infection of the embryo is not essential for fetal demise. Our immunologically unmanipulated pregnancy mouse model provides a consistent and easily measurable congenital abnormality readout to assess fetal outcome, and may serve as an additional model to test prophylactic and therapeutic interventions to protect the fetus during pregnancy, and for studying the mechanisms of ZIKV congenital immunopathogenesis. PMID:29634758

  5. Vaccination against lymphocytic choriomeningitis virus infection in MHC class II-deficient mice

    DEFF Research Database (Denmark)

    Holst, Peter Johannes; Christensen, Jan Pravsgaard; Thomsen, Allan Randrup

    2011-01-01

    response could be elicited in MHC class II-deficient mice by vaccination with adenovirus encoding lymphocytic choriomeningitis virus (LCMV) glycoprotein tethered to MHC class II-associated invariant chain. Moreover, the response induced conferred significant cytolytic CD8(+) T cell-mediated protection...... against challenge with a high dose of the invasive clone 13 strain of LCMV. In contrast, vaccination with adenovirus encoding unlinked LCMV glycoprotein induced weak virus control in the absence of CD4(+) T cells, and mice may die of increased immunopathology associated with incomplete protection. Acute...... mortality was not observed in any vaccinated mice following infection with the less-invasive Traub strain. However, LCMV Traub infection caused accelerated late mortality in unvaccinated MHC class II-deficient mice; in this case, we observed a strong trend toward delayed mortality in vaccinated mice...

  6. Lymphocyte proliferation in Peyer's patches of Giardia muris-infected mice.

    OpenAIRE

    Hill, D R

    1990-01-01

    Gastrointestinal immune events in giardiasis are important in controlling infection. In this study, Peyer's patch lymphocytes from mice infected with Giardia muris developed specific, proliferative responses to G. muris antigen. This proliferation correlated with clearance of infection. Further understanding of the gut immune response will be helpful in developing immunoprophylactic strategies in the control of giardiasis.

  7. Critical Role of Airway Macrophages in Modulating Disease Severity during Influenza Virus Infection of Mice

    Science.gov (United States)

    Tate, Michelle D.; Pickett, Danielle L.; van Rooijen, Nico; Brooks, Andrew G.; Reading, Patrick C.

    2010-01-01

    Airway macrophages provide a first line of host defense against a range of airborne pathogens, including influenza virus. In this study, we show that influenza viruses differ markedly in their abilities to infect murine macrophages in vitro and that infection of macrophages is nonproductive and no infectious virus is released. Virus strain BJx109 (H3N2) infected macrophages with high efficiency and was associated with mild disease following intranasal infection of mice. In contrast, virus strain PR8 (H1N1) was poor in its ability to infect macrophages and highly virulent for mice. Depletion of airway macrophages by clodronate-loaded liposomes led to the development of severe viral pneumonia in BJx109-infected mice but did not modulate disease severity in PR8-infected mice. The severe disease observed in macrophage-depleted mice infected with BJx109 was associated with exacerbated virus replication in the airways, leading to severe airway inflammation, pulmonary edema, and vascular leakage, indicative of lung injury. Thymic atrophy, lymphopenia, and dysregulated cytokine and chemokine production were additional systemic manifestations associated with severe disease. Thus, airway macrophages play a critical role in limiting lung injury and associated disease caused by BJx109. Furthermore, the inability of PR8 to infect airway macrophages may be a critical factor contributing to its virulence for mice. PMID:20504924

  8. Acute HBV infection in humanized chimeric mice has multiphasic viral kinetics.

    Science.gov (United States)

    Ishida, Yuji; Chung, Tje Lin; Imamura, Michio; Hiraga, Nobuhiko; Sen, Suranjana; Yokomichi, Hiroshi; Tateno, Chise; Canini, Laetitia; Perelson, Alan S; Uprichard, Susan L; Dahari, Harel; Chayama, Kazuaki

    2018-03-23

    Chimeric uPA/SCID mice reconstituted with humanized livers are useful for studying HBV infection in the absence of an adaptive immune response. However, the detailed characterization of HBV infection kinetics necessary to enable in-depth mechanistic studies in this novel in vivo HBV infection model is lacking. To characterize HBV kinetics post-inoculation (p.i.) to steady state, 42 mice were inoculated with HBV. Serum HBV DNA was frequently measured from 1 minute to 63 days p.i. Total intrahepatic HBV DNA, HBV cccDNA, and HBV RNA was measured in a subset of mice at 2, 4, 6, 10, and 13 weeks p.i. HBV half-life (t 1/2 ) was estimated using a linear mixed-effects model. During the first 6 h p.i. serum HBV declined in repopulated uPA/SCID mice with a t 1/2 =62 min [95%CI=59-67min]. Thereafter, viral decline slowed followed by a 2 day lower plateau. Subsequent viral amplification was multiphasic with an initial mean doubling time of t 2 =8±3 h followed by an interim plateau before prolonged amplification (t 2 =2±0.5 days) to a final HBV steady state of 9.3±0.3 log copies/ml. Serum HBV and intrahepatic HBV DNA were positively correlated (R 2 =0.98). HBV infection in uPA/SCID chimeric mice is highly dynamic despite the absence of an adaptive immune response. The serum HBV t 1/2 in humanized uPA/SCID mice was estimated to be ∼1 h regardless of inoculum size. The HBV acute infection kinetics presented here is an important step in characterizing this experimental model system so that it can be effectively used to elucidate the dynamics of the HBV lifecycle and thus possibly reveal effective antiviral drug targets. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

  9. Chronic Co-species Housing Mice and Rats Increased the Competitiveness of Male Mice.

    Science.gov (United States)

    Liu, Ying-Juan; Li, Lai-Fu; Zhang, Yao-Hua; Guo, Hui-Fen; Xia, Min; Zhang, Meng-Wei; Jing, Xiao-Yuan; Zhang, Jing-Hua; Zhang, Jian-Xu

    2017-03-01

    Rats are predators of mice in nature. Nevertheless, it is a common practice to house mice and rats in a same room in some laboratories. In this study, we investigated the behavioral and physiological responsively of mice in long-term co-species housing conditions. Twenty-four male mice were randomly assigned to their original raising room (control) or a rat room (co-species-housed) for more than 6 weeks. In the open-field and light-dark box tests, the behaviors of the co-species-housed mice and controls were not different. In a 2-choice test of paired urine odors [rabbit urine (as a novel odor) vs. rat urine, cat urine (as a natural predator-scent) vs. rabbit urine, and cat urine vs. rat urine], the co-species-housed mice were more ready to investigate the rat urine odor compared with the controls and may have adapted to it. In an encounter test, the rat-room-exposed mice exhibited increased aggression levels, and their urines were more attractive to females. Correspondingly, the levels of major urinary proteins were increased in the co-species-housed mouse urine, along with some volatile pheromones. The serum testosterone levels were also enhanced in the co-species-housed mice, whereas the corticosterone levels were not different. The norepinephrine, dopamine, and 5-HT levels in the right hippocampus and striatum were not different between the 2. Our findings indicate that chronic co-species housing results in adaptation in male mice; furthermore, it appears that long-term rat-odor stimuli enhance the competitiveness of mice, which suggests that appropriate predator-odor stimuli may be important to the fitness of prey animals. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Mechanism of infectivity of a murine leukemia virus in adult mice

    International Nuclear Information System (INIS)

    Levy, R.L.; Barrington, M.H.; Lerner, R.A.; Dixon, F.J.

    1976-01-01

    Infection of adult BALB/c mice with murine leukemia virus (MuLV) induces typical thymic lymphomas. Expression of virus was measured by using a radioimmunoassay for murine P-30, a virion core protein. Nineteen days after injection of MuLV-S into adult mice, there were 0.3μg P-30/ml of serum. X-irradiation permitted the early expression of high levels of viremia, when given before or after MuLV-S administration, and it also hastened the development of lymphomas. Seventeen to 21 days after injection of MuLV-S into x-irradiated (600 rads) adult mice, there were 2.7 μg of P-30/ml of serum. The virus produced by infected adult mice was infectious and oncogenic when given to newborn mice. Several lines of evidence are presented that suggest the mechanism by which x-irradiation permits early expession of virion proteins and lymphomas is not immunosuppression

  11. Characterization of Lethal Zika Virus Infection in AG129 Mice.

    Directory of Open Access Journals (Sweden)

    Matthew T Aliota

    2016-04-01

    Full Text Available Mosquito-borne Zika virus (ZIKV typically causes a mild and self-limiting illness known as Zika fever, which often is accompanied by maculopapular rash, headache, and myalgia. During the current outbreak in South America, ZIKV infection during pregnancy has been hypothesized to cause microcephaly and other diseases. The detection of ZIKV in fetal brain tissue supports this hypothesis. Because human infections with ZIKV historically have remained sporadic and, until recently, have been limited to small-scale epidemics, neither the disease caused by ZIKV nor the molecular determinants of virulence and/or pathogenicity have been well characterized. Here, we describe a small animal model for wild-type ZIKV of the Asian lineage.Using mice deficient in interferon α/β and Ɣ receptors (AG129 mice, we report that these animals were highly susceptible to ZIKV infection and disease, succumbing within seven to eight days. Rapid viremic dissemination was observed in visceral organs and brain; but only was associated with severe pathologies in the brain and muscle. Finally, these results were consistent across challenge routes, age of mice, and inoculum doses. These data represent a mouse model for ZIKV that is not dependent on adapting ZIKV to intracerebral passage in mice.Foot pad injection of AG129 mice with ZIKV represents a biologically relevant model for studying ZIKV infection and disease development following wild-type virus inoculation without the requirement for adaptation of the virus or intracerebral delivery of the virus. This newly developed Zika disease model can be exploited to identify determinants of ZIKV virulence and reveal molecular mechanisms that control the virus-host interaction, providing a framework for rational design of acute phase therapeutics and for vaccine efficacy testing.

  12. The antiviral effectiveness of butylated hydroxytoluene on herpes cutaneous infections in hairless mice

    International Nuclear Information System (INIS)

    Keith, A.D.; Arruda, D.; Snipes, W.; Frost, P.

    1982-01-01

    Hairless mice, cutaneously infected with herpes simplex virus type 1 (HSV-1), were treated topically with butylated hydroxytoluene (BHT). The effectiveness of BHT in shortening the duration of infections was assayed under three conditions. In the first experiments, mice undergoing primary infections with no prior immunity to HSV-1 were utilized. These animals tended to develop deep lesions that were not typical of recurrent HSV-1 infections in humans. A second set of experiments utilized mice that had recovered from a primary infection and that were immunosuppressed by γ irradiation. Immunosuppression was essential for the full development of lesions upon reinfection. The lesions in these animals remained more localized with less tendency to spread into deep tissues. A third set of experiments utilized animals that were subcutaneously inoculated with human serum γ-globulin 24 hr prior to infection. Lesions on these animals also remained localized and did not penetrate into deep tissues. Under all three conditions, BHT was found to be effective in reducing the clearance time of HSV-1 cutaneous lesions when applied topically to the infected area

  13. High infection control rate and function after routine one-stage exchange for chronically infected TKA.

    Science.gov (United States)

    Jenny, Jean-Yves; Barbe, Bruno; Gaudias, Jeannot; Boeri, Cyril; Argenson, Jean-Noël

    2013-01-01

    Many surgeons consider two-stage exchange the gold standard for treating chronic infection after TKA. One-stage exchange is an alternative for infection control and might provide better knee function, but the rates of infection control and levels of function are unclear. We asked whether a one-stage exchange protocol would lead to infection control rates and knee function similar to those after two-stage exchange. We followed all 47 patients with chronically infected TKAs treated with one-stage exchange between July 2004 and February 2007. We monitored for recurrence of infection and obtained Knee Society Scores. We followed patients a minimum of 3 years or until death or infection recurrence. Three of the 47 patients (6%) experienced a persistence or recurrence of the index infection with the same pathogen isolated. Three patients (6%) had control of the index infection but between 6 and 17 months experienced an infection with another pathogen. The 3-year survival rates were 87% for being free of any infection and 91% for being healed of the index infection. Twenty-five of the 45 patients (56%) had a Knee Society Score of more than 150 points. While routine one-stage exchange was not associated with a higher rate of infection recurrence failure, knee function was not improved compared to that of historical patients having two-stage exchange. One stage-exchange may be a reasonable alternative in chronically infected TKA as a more convenient approach for patients without the risks of two operations and hospitalizations and for reducing costs. The ideal one stage-exchange candidate should be identified in future studies.

  14. Dysfunction of mitochondrial dynamics in the brains of scrapie-infected mice

    International Nuclear Information System (INIS)

    Choi, Hong-Seok; Choi, Yeong-Gon; Shin, Hae-Young; Oh, Jae-Min; Park, Jeong-Ho; Kim, Jae-Il; Carp, Richard I.; Choi, Eun-Kyoung; Kim, Yong-Sun

    2014-01-01

    Highlights: • Mfn1 and Fis1 are significantly increased in the hippocampal region of the ME7 prion-infected brain, whereas Dlp1 is significantly decreased in the infected brain. • Dlp1 is significantly decreased in the cytosolic fraction of the hippocampus in the infected brain. • Neuronal mitochondria in the prion-infected brains are enlarged and swollen compared to those of control brains. • There are significantly fewer mitochondria in the ME7-infected brain compared to the number in control brain. - Abstract: Mitochondrial dysfunction is a common and prominent feature of many neurodegenerative diseases, including prion diseases; it is induced by oxidative stress in scrapie-infected animal models. In previous studies, we found swelling and dysfunction of mitochondria in the brains of scrapie-infected mice compared to brains of controls, but the mechanisms underlying mitochondrial dysfunction remain unclear. To examine whether the dysregulation of mitochondrial proteins is related to the mitochondrial dysfunction associated with prion disease, we investigated the expression patterns of mitochondrial fusion and fission proteins in the brains of ME7 prion-infected mice. Immunoblot analysis revealed that Mfn1 was up-regulated in both whole brain and specific brain regions, including the cerebral cortex and hippocampus, of ME7-infected mice compared to controls. Additionally, expression levels of Fis1 and Mfn2 were elevated in the hippocampus and the striatum, respectively, of the ME7-infected brain. In contrast, Dlp1 expression was significantly reduced in the hippocampus in the ME7-infected brain, particularly in the cytosolic fraction. Finally, we observed abnormal mitochondrial enlargement and histopathological change in the hippocampus of the ME7-infected brain. These observations suggest that the mitochondrial dysfunction, which is presumably caused by the dysregulation of mitochondrial fusion and fission proteins, may contribute to the

  15. Dysfunction of mitochondrial dynamics in the brains of scrapie-infected mice

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Hong-Seok [Department of Microbiology, College of Medicine, Hallym University, 1 Okcheon-dong, Chuncheon, Gangwon-do 200-702 (Korea, Republic of); Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060 (Korea, Republic of); Choi, Yeong-Gon; Shin, Hae-Young; Oh, Jae-Min [Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060 (Korea, Republic of); Park, Jeong-Ho [Department of Microbiology, College of Medicine, Hallym University, 1 Okcheon-dong, Chuncheon, Gangwon-do 200-702 (Korea, Republic of); Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060 (Korea, Republic of); Kim, Jae-Il [Department of Food Science and Nutrition, Pukyong National University, 599-1 Daeyeon-3-dong, Nam-gu, Busan 608-737 (Korea, Republic of); Carp, Richard I. [New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314 (United States); Choi, Eun-Kyoung, E-mail: ekchoi@hallym.ac.kr [Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060 (Korea, Republic of); Kim, Yong-Sun, E-mail: yskim@hallym.ac.kr [Department of Microbiology, College of Medicine, Hallym University, 1 Okcheon-dong, Chuncheon, Gangwon-do 200-702 (Korea, Republic of); Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060 (Korea, Republic of)

    2014-05-30

    Highlights: • Mfn1 and Fis1 are significantly increased in the hippocampal region of the ME7 prion-infected brain, whereas Dlp1 is significantly decreased in the infected brain. • Dlp1 is significantly decreased in the cytosolic fraction of the hippocampus in the infected brain. • Neuronal mitochondria in the prion-infected brains are enlarged and swollen compared to those of control brains. • There are significantly fewer mitochondria in the ME7-infected brain compared to the number in control brain. - Abstract: Mitochondrial dysfunction is a common and prominent feature of many neurodegenerative diseases, including prion diseases; it is induced by oxidative stress in scrapie-infected animal models. In previous studies, we found swelling and dysfunction of mitochondria in the brains of scrapie-infected mice compared to brains of controls, but the mechanisms underlying mitochondrial dysfunction remain unclear. To examine whether the dysregulation of mitochondrial proteins is related to the mitochondrial dysfunction associated with prion disease, we investigated the expression patterns of mitochondrial fusion and fission proteins in the brains of ME7 prion-infected mice. Immunoblot analysis revealed that Mfn1 was up-regulated in both whole brain and specific brain regions, including the cerebral cortex and hippocampus, of ME7-infected mice compared to controls. Additionally, expression levels of Fis1 and Mfn2 were elevated in the hippocampus and the striatum, respectively, of the ME7-infected brain. In contrast, Dlp1 expression was significantly reduced in the hippocampus in the ME7-infected brain, particularly in the cytosolic fraction. Finally, we observed abnormal mitochondrial enlargement and histopathological change in the hippocampus of the ME7-infected brain. These observations suggest that the mitochondrial dysfunction, which is presumably caused by the dysregulation of mitochondrial fusion and fission proteins, may contribute to the

  16. [Calbindin and parvalbumin distribution in spinal cord of normal and rabies-infected mice].

    Science.gov (United States)

    Monroy-Gómez, Jeison; Torres-Fernández, Orlando

    2013-01-01

    Rabies is a fatal infectious disease of the nervous system; however, the knowledge about the pathogenic neural mechanisms in rabies is scarce. In addition, there are few studies of rabies pathology of the spinal cord. To study the distribution of calcium binding proteins calbindin and parvalbumin and assessing the effect of rabies virus infection on their expression in the spinal cord of mice. MATERIALES Y METHODS: Mice were inoculated with rabies virus, by intracerebral or intramuscular route. The spinal cord was extracted to perform some crosscuts which were treated by immunohistochemistry with monoclonal antibodies to reveal the presence of the two proteins in normal and rabies infected mice. We did qualitative and quantitative analyses of the immunoreactivity of the two proteins. Calbindin and parvalbumin showed differential distribution in Rexed laminae. Rabies infection produced a decrease in the expression of calbindin. On the contrary, the infection caused an increased expression of parvalbumin. The effect of rabies infection on the two proteins expression was similar when comparing both routes of inoculation. The differential effect of rabies virus infection on the expression of calbindin and parvalbumin in the spinal cord of mice was similar to that previously reported for brain areas. This result suggests uniformity in the response to rabies infection throughout the central nervous system. This is an important contribution to the understanding of the pathogenesis of rabies.

  17. Chronic high fat diet induces cardiac hypertrophy and fibrosis in mice.

    Science.gov (United States)

    Wang, Zhi; Li, Liaoliao; Zhao, Huijuan; Peng, Shuling; Zuo, Zhiyi

    2015-08-01

    Obesity can cause pathological changes in organs. We determined the effects of chronic high fat diet (HFD) and intermittent fasting, a paradigm providing organ protection, on mouse heart. Seven-week old CD1 male mice were randomly assigned to control, HFD and intermittent fasting groups. Control mice had free access to regular diet (RD). RD was provided every other day to mice in the intermittent fasting group. Mice in HFD group had free access to HFD. Their left ventricles were harvested 11 months after they had been on these diet regimens. HFD increased cardiomyocyte cross-section area and fibrosis. HFD decreased active caspase 3, an apoptosis marker, and the ratio of microtubule-associated protein 1A/1B-light chain 3 (LC3) II/LC3I, an autophagy marker. HFD increased the phospho-glycogen synthase kinase-3β (GSK-3β) at Ser9, a sign of GSK-3β inhibition. Nuclear GATA binding protein 4 and yes-associated protein, two GSK-3β targeting transcription factors that can induce hypertrophy-related gene expression, were increased in HFD-fed mice. Mice on intermittent fasting did not have these changes except for the increased active caspase 3 and decreased ratio of LC3II/LC3I. These results suggest that chronic HFD induces myocardial hypertrophy and fibrosis, which may be mediated by GSK-3β inhibition. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Bystander chronic infection negatively impacts development of CD8+ T cell memory

    Science.gov (United States)

    Stelekati, Erietta; Shin, Haina; Doering, Travis A.; Dolfi, Douglas V.; Ziegler, Carly G.; Beiting, Daniel P.; Dawson, Lucas; Liboon, Jennifer; Wolski, David; Ali, Mohammed-Alkhatim A.; Katsikis, Peter D.; Shen, Hao; Roos, David S.; Haining, W. Nicholas; Lauer, Georg M.; Wherry, E. John

    2014-01-01

    Summary Epidemiological evidence suggests that chronic infections impair immune responses to unrelated pathogens and vaccines. The underlying mechanisms, however, are unclear and distinguishing effects on priming versus development of immunological memory has been challenging. We investigated whether bystander chronic infections impact differentiation of memory CD8+ T cells, the hallmark of protective immunity against intracellular pathogens. Chronic bystander infections impaired development of memory CD8+ T cells in several mouse models and humans. These effects were independent of initial priming and were associated with chronic inflammatory signatures. Chronic inflammation negatively impacted the number of bystander CD8+ T cells and their memory development. Distinct underlying mechanisms of altered survival and differentiation were revealed with the latter regulated by the transcription factors T-bet and Blimp-1. Thus, exposure to prolonged bystander inflammation impairs the effector to memory transition. These data have relevance for immunity and vaccination during persisting infections and chronic inflammation. PMID:24837104

  19. Adrenocortical and behavioural response to chronic restraint stress in neurokinin-1 receptor knockout mice.

    Science.gov (United States)

    Delgado-Morales, Raúl; del Río, Eva; Gómez-Román, Almudena; Bisagno, Verónica; Nadal, Roser; de Felipe, Carmen; Armario, Antonio

    2012-02-01

    Brain substance P and its receptor (neurokinin-1, NK1) have a widespread brain distribution and are involved in an important number of behavioural and physiological responses to emotional stimuli. However, the role of NK1 receptors in the consequences of exposure to chronic stress has not been explored. The present study focused on the role of these receptors in the hypothalamic-pituitary-adrenal (HPA) response to daily repeated restraint stress (evaluated by plasma corticosterone levels), as well as on the effect of this procedure on anxiety-like behaviour, spatial learning and memory in the Morris water maze (MWM), a hippocampus-dependent task. Adult null mutant NK1-/- mice, with a C57BL/6J background, and the corresponding wild-type mice showed similar resting corticosterone levels and, also, did not differ in corticosterone response to a first restraint. Nevertheless, adaptation to the repeated stressor was faster in NK1-/- mice. Chronic restraint modestly increased anxiety-like behaviour in the light-dark test, irrespective of genotype. Throughout the days of the MWM trials, NK1-/- mice showed a similar learning rate to that of wild-type mice, but had lower levels of thigmotaxis and showed a better retention in the probe trial. Chronic restraint stress did not affect these variables in either genotype. These results indicate that deletion of the NK1 receptor does not alter behavioural susceptibility to chronic repeated stress in mice, but accelerates adaptation of the HPA axis. In addition, deletion may result in lower levels of thigmotaxis and improved short-term spatial memory, perhaps reflecting a better learning strategy in the MWM. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. [Comorbidities as risk factors of chronic kidney disease in HIV-infected persons].

    Science.gov (United States)

    Marchewka, Zofia; Szymczak, Aleksandra; Knysz, Brygida

    2015-12-16

    Significant survival prolongation in HIV-infected patients due to effective antiretroviral therapy is connected with increasing prevalence of chronic non-infective diseases in this population, among them chronic kidney disease. The pathogenesis of kidney disease in the setting of HIV includes conditions specific for HIV infection: direct effect of the virus, stage of immunodeficiency and drug toxicity. Chronic comorbidities, such as diabetes mellitus, hypertension, and hyperlipidemia, are additional significant risk factors of kidney disease. In HIV-infected individuals some distinct features of these conditions are observed, which are partly related to the virus and antiretroviral therapy. The article summarizes the effect of comorbidities on kidney function in HIV-infected persons.

  1. Evolution of sarcoma 180 (ascitic tumor in mice infected with Schistosoma mansoni

    Directory of Open Access Journals (Sweden)

    Fausto Edmundo Lima Pereira

    1986-03-01

    Full Text Available Mice infected with 60 cercariae of Schistosoma mansoni were more resistant to the sarcoma 180 ascites tumor. Tumor inoculation was performed 50 days after schistosoma infection and the animals were observed and weighed at 48 hours intervals for development and progression of malignancy. In infected mice the weight gain (ascites formation started later and was shorter than in uninfected Controls. Also, the number of tumor cells into the peritoneal cavity 72h after tumor implantation was shorter in infected group than incontrols. This in creased resistance against a transplantable tumor probably is related to the effect of endotoxin on tumoricidal activity of macrophages activated by the infection. The immunodepression induced by Schistosoma mansoni infection enhances the proliferation of endogenous bacteria increasing the amount of endotoxin absorbed from the gut.

  2. A lung segmental model of chronic Pseudomonas infection in sheep.

    Directory of Open Access Journals (Sweden)

    David Collie

    Full Text Available Chronic lung infection with Pseudomonas aeruginosa is a major contributor to morbidity, mortality and premature death in cystic fibrosis. A new paradigm for managing such infections is needed, as are relevant and translatable animal models to identify and test concepts. We sought to improve on limitations associated with existing models of infection in small animals through developing a lung segmental model of chronic Pseudomonas infection in sheep.Using local lung instillation of P. aeruginosa suspended in agar beads we were able to demonstrate that such infection led to the development of a suppurative, necrotising and pyogranulomatous pneumonia centred on the instilled beads. No overt evidence of organ or systemic compromise was apparent in any animal during the course of infection. Infection persisted in the lungs of individual animals for as long as 66 days after initial instillation. Quantitative microbiology applied to bronchoalveolar lavage fluid derived from infected segments proved an insensitive index of the presence of significant infection in lung tissue (>10(4 cfu/g.The agar bead model of chronic P. aeruginosa lung infection in sheep is a relevant platform to investigate both the pathobiology of such infections as well as novel approaches to their diagnosis and therapy. Particular ethical benefits relate to the model in terms of refining existing approaches by compromising a smaller proportion of the lung with infection and facilitating longitudinal assessment by bronchoscopy, and also potentially reducing animal numbers through facilitating within-animal comparisons of differential therapeutic approaches.

  3. A lung segmental model of chronic Pseudomonas infection in sheep.

    Science.gov (United States)

    Collie, David; Govan, John; Wright, Steven; Thornton, Elisabeth; Tennant, Peter; Smith, Sionagh; Doherty, Catherine; McLachlan, Gerry

    2013-01-01

    Chronic lung infection with Pseudomonas aeruginosa is a major contributor to morbidity, mortality and premature death in cystic fibrosis. A new paradigm for managing such infections is needed, as are relevant and translatable animal models to identify and test concepts. We sought to improve on limitations associated with existing models of infection in small animals through developing a lung segmental model of chronic Pseudomonas infection in sheep. Using local lung instillation of P. aeruginosa suspended in agar beads we were able to demonstrate that such infection led to the development of a suppurative, necrotising and pyogranulomatous pneumonia centred on the instilled beads. No overt evidence of organ or systemic compromise was apparent in any animal during the course of infection. Infection persisted in the lungs of individual animals for as long as 66 days after initial instillation. Quantitative microbiology applied to bronchoalveolar lavage fluid derived from infected segments proved an insensitive index of the presence of significant infection in lung tissue (>10(4) cfu/g). The agar bead model of chronic P. aeruginosa lung infection in sheep is a relevant platform to investigate both the pathobiology of such infections as well as novel approaches to their diagnosis and therapy. Particular ethical benefits relate to the model in terms of refining existing approaches by compromising a smaller proportion of the lung with infection and facilitating longitudinal assessment by bronchoscopy, and also potentially reducing animal numbers through facilitating within-animal comparisons of differential therapeutic approaches.

  4. Increased Susceptibility of Humanized NSG Mice to Panton-Valentine Leukocidin and Staphylococcus aureus Skin Infection.

    Directory of Open Access Journals (Sweden)

    Ching Wen Tseng

    Full Text Available Staphylococcus aureus is a leading cause of skin and soft-tissue infections worldwide. Mice are the most commonly used animals for modeling human staphylococcal infections. However a supra-physiologic S. aureus inoculum is required to establish gross murine skin pathology. Moreover, many staphylococcal factors, including Panton-Valentine leukocidin (PVL elaborated by community-associated methicillin-resistant S. aureus (CA-MRSA, exhibit selective human tropism and cannot be adequately studied in mice. To overcome these deficiencies, we investigated S. aureus infection in non-obese diabetic (NOD/severe combined immune deficiency (SCID/IL2rγnull (NSG mice engrafted with human CD34+ umbilical cord blood cells. These "humanized" NSG mice require one to two log lower inoculum to induce consistent skin lesions compared with control mice, and exhibit larger cutaneous lesions upon infection with PVL+ versus isogenic PVL- S. aureus. Neutrophils appear important for PVL pathology as adoptive transfer of human neutrophils alone to NSG mice was sufficient to induce dermonecrosis following challenge with PVL+ S. aureus but not PVL- S. aureus. PMX53, a human C5aR inhibitor, blocked PVL-induced cellular cytotoxicity in vitro and reduced the size difference of lesions induced by the PVL+ and PVL- S. aureus, but PMX53 also reduced recruitment of neutrophils and exacerbated the infection. Overall, our findings establish humanized mice as an important translational tool for the study of S. aureus infection and provide strong evidence that PVL is a human virulence factor.

  5. Taenia crassiceps Infection Attenuates Multiple Low-Dose Streptozotocin-Induced Diabetes

    Directory of Open Access Journals (Sweden)

    Arlett Espinoza-Jiménez

    2010-01-01

    Full Text Available Taenia crassiceps, like other helminths, can exert regulatory effects on the immune system of its host. This study investigates the effect of chronic T. crassiceps infection on the outcome of Multiple Low Dose Streptozotocin-Induced Diabetes (MLDS. Healthy or previously T. crassiceps-infected mice received MLDS and type 1 diabetes (T1D symptoms were evaluated for 6 weeks following the induction of MLDS. T. crassiceps-infected mice displayed lower blood glucose levels throughout the study. A significantly lower percentage of T. crassiceps-infected mice (40% developed T1D compared to the uninfected group (100%. Insulitis was remarkably absent in T. crassiceps-infected mice, which had normal pancreatic insulin content, whereas uninfected mice showed a dramatic reduction in pancreatic insulin. Infected mice that received MLDS did not show an increase in their regulatory T cell population, however, they had a greater number of alternatively activated macrophages, higher levels of the cytokine IL-4, and lower levels of TNF-α. Therefore, infection with T. crassiceps causes an immunomodulation that modifies the incidence and development of MLDS-induced autoimmune diabetes.

  6. The Acute Phase of Trypanosoma cruzi Infection Is Attenuated in 5-Lipoxygenase-Deficient Mice

    Directory of Open Access Journals (Sweden)

    Adriana M. C. Canavaci

    2014-01-01

    Full Text Available In the present work we examine the contribution of 5-lipoxygenase- (5-LO- derived lipid mediators to immune responses during the acute phase of Trypanosoma cruzi infection in 5-LO gene knockout (5-LO−/− mice and wild-type (WT mice. Compared with WT mice, the 5-LO−/− mice developed less parasitemia/tissue parasitism, less inflammatory cell infiltrates, and a lower mortality. This resistance of 5-LO−/− mice correlated with several differences in the immune response to infection, including reduced PGE2 synthesis; sustained capacity of splenocytes to produce high levels of interleukin (IL-12 early in the infection; enhanced splenocyte production of IL-1β, IL-6, and IFN-γ; rapid T-cell polarization to secrete high quantities of IFN-γ and low quantities of IL-10; and greater numbers of CD8+CD44highCD62Llow memory effector T cells at the end of the acute phase of infection. The high mortality in WT mice was associated with increased production of LTB4/LTC4, T cell bias to produce IFN-γ, high levels of serum nitrite, and marked protein extravasation into the peritoneal cavity, although survival was improved by treatment with a cys-LT receptor 1 antagonist. These data also provide evidence that 5-LO-derived mediators negatively affect host survival during the acute phase of T. cruzi infection.

  7. Course of induced infection by Eimeria krijgsmannni in immunocompetent and immunodeficient mice.

    Science.gov (United States)

    Ono, Yuina; Matsubayashi, Makoto; Kawaguchi, Hiroaki; Tsujio, Masashi; Mizuno, Masanobu; Tanaka, Tetsuya; Masatani, Tatsunori; Matsui, Toshihiro; Matsuo, Tomohide

    2016-01-01

    Recently, we have demonstrated the utility of Eimeria krijgsmanni as a novel mouse eimerian parasite for elucidating the biological diversity. The parasite showed notable infectivity to mice with various levels of immune status and susceptibility to antimicrobial agents including coccidiostat. However, the detailed lifecycle of E. krijgsmanni had not yet been determined and this information was lacking in discussion of previous findings. In the present study, we clarified the morphological characteristics of E. krijgsmanni and its lifecycle in normal mice, and examined the effects in immunodeficient mice and lifecycle stage for challenge infections after the primary inoculation. In immunocompetent mice, the lifecycle consisted of four asexual stages and the sexual sages followed by formation of oocysts during the prepatent periods. Interestingly, the second-generation meronts were detected in all observation periods after the disappearance of the other stages. For the challenge infection of immunodeficient mice, all developmental stages except for the second generation meronts were temporarily vanished. This finding suggests a "rest" or marked delay in development and a "restart" of the promotion toward the next generations. The second generation meronts may play an important role in the lifecycle of E. krijgsmanni.

  8. Decay-accelerating factor 1 deficiency exacerbates leptospiral-induced murine chronic nephritis and renal fibrosis.

    Directory of Open Access Journals (Sweden)

    María F Ferrer

    Full Text Available Leptospirosis is a global zoonosis caused by pathogenic Leptospira, which can colonize the proximal renal tubules and persist for long periods in the kidneys of infected hosts. Here, we characterized the infection of C57BL/6J wild-type and Daf1-/- mice, which have an enhanced host response, with a virulent Leptospira interrogans strain at 14 days post-infection, its persistence in the kidney, and its link to kidney fibrosis at 90 days post-infection. We found that Leptospira interrogans can induce acute moderate nephritis in wild-type mice and is able to persist in some animals, inducing fibrosis in the absence of mortality. In contrast, Daf1-/- mice showed acute mortality, with a higher bacterial burden. At the chronic stage, Daf1-/- mice showed greater inflammation and fibrosis than at 14 days post-infection and higher levels at all times than the wild-type counterpart. Compared with uninfected mice, infected wild-type mice showed higher levels of IL-4, IL-10 and IL-13, with similar levels of α-smooth muscle actin, galectin-3, TGF-β1, IL-17, IFN-γ, and lower IL-12 levels at 90 days post-infection. In contrast, fibrosis in Daf1-/- mice was accompanied by high expression of α-smooth muscle actin, galectin-3, IL-10, IL-13, and IFN-γ, similar levels of TGF-β1, IL-12, and IL-17 and lower IL-4 levels. This study demonstrates the link between Leptospira-induced murine chronic nephritis with renal fibrosis and shows a protective role of Daf1.

  9. Improved outcome of chronic Pseudomonas aeruginosa lung infection is associated with induction of a Th1-dominated cytokine response

    DEFF Research Database (Denmark)

    Moser, C; Jensen, P O; Kobayashi, O

    2002-01-01

    patients, the lungs of susceptible BALB/c mice were re-infected with P. aeruginosa 14 days after the initial infection. Singly-infected BALB/c mice, as well as non-infected mice, were used as controls. Decreased mortality and milder lung inflammation in re-infected BALB/c mice, as well as a tendency...

  10. Subcutaneous infection model facilitates treatment assessment of secondary Alveolar echinococcosis in mice.

    Directory of Open Access Journals (Sweden)

    Tatiana Küster

    Full Text Available Alveolar echinococcosis (AE in humans is a parasitic disease characterized by severe damage to the liver and occasionally other organs. AE is caused by infection with the metacestode (larval stage of the fox tapeworm Echinococcus multilocularis, usually infecting small rodents as natural intermediate hosts. Conventionally, human AE is chemotherapeutically treated with mebendazole or albendazole. There is, however still the need for improved chemotherapeutical options. Primary in vivo studies on drugs of interest are commonly performed in small laboratory animals such as mice and Mongolian jirds, and in most cases, a secondary infection model is used, whereby E. multilocularis metacestodes are directly injected into the peritoneal cavity or into the liver. Disadvantages of this methodological approach include risk of injury to organs during the inoculation and, most notably, a limitation in the macroscopic (visible assessment of treatment efficacy. Thus, in order to monitor the efficacy of chemotherapeutical treatment, animals have to be euthanized and the parasite tissue dissected. In the present study, mice were infected with E. multilocularis metacestodes through the subcutaneous route and were then subjected to chemotherapy employing albendazole. Serological responses to infection were comparatively assessed in mice infected by the conventional intraperitoneal route. We demonstrate that the subcutaneous infection model for secondary AE facilitates the assessment of the progress of infection and drug treatment in the live animal.

  11. Chronic prostatic infection and inflammation by Propionibacterium acnes in a rat prostate infection model.

    Science.gov (United States)

    Olsson, Jan; Drott, Johanna Bergh; Laurantzon, Lovisa; Laurantzon, Oscar; Bergh, Anders; Elgh, Fredrik

    2012-01-01

    Chronic inflammation in the prostate, seen as infiltration of inflammatory cells into the prostate gland in histological samples, affects approximately half the male population without indication of prostate disease, and is almost ubiquitous in patients diagnosed with benign prostate hyperplasia and cancer. Several studies have demonstrated the gram-positive bacterium Propionibacterium acnes to be frequently present in prostate tissue from men suffering from prostate disease. P. acnes has been shown to be associated with histological inflammation in human prostatectomy specimens, and also to induce strong inflammatory response in prostate-derived tissue culture models. The present paper describes a rat model for assessment of the pathogenic potential of P. acnes in prostate. Prostate glands of Sprague Dawley rats (n = 98) were exposed via an abdominal incision and live P. acnes or, in control rats, saline were injected into the ventral and dorso-lateral lobes. Rats were sacrificed 5 days, 3 weeks, 3 months and 6 months post infection, and prostate tissue was analyzed for bacterial content and histological inflammation. Rat sera were assessed for levels of CRP and anti-P. acnes IgG. Live P. acnes could be recovered from the dorso-lateral lobes up to 3 months post infection, while the ventral lobes were cleared from bacteria at that time. In samples up to 3 months post infection, the dorso-lateral lobes exhibited intense focal inflammation. CRP and IgG levels were elevated throughout the span of the experiment, and reached maximum levels 3 weeks and 3 months post infection, respectively. We show that P. acnes have the potential to cause chronic infection in previously healthy prostate, and that the infection has potential to cause chronic histological inflammation in the infected tissue. The high prevalence of P. acnes in human prostate tissue calls for resolution of pathogenic details. The present rat model suggests that complications such as chronic

  12. The role of helicobacter pylori infection in the pathogenesis of chronic urticaria

    International Nuclear Information System (INIS)

    Ghazzawi, I.M.; Obidat, N.A.

    2004-01-01

    Objective: To determine the prevalence of H. pylori infection in patients with idiopathic chronic urticaria (ICU) and to see if eradication of the bacterium affects the course of the urticaria. Patients and Methods: One hundred patients with idiopathic chronic urticaria and 43 healthy subjects (matched for age and sex) underwent serological testing for H. pylori infection. All patients with idiopathic chronic urticaria were examined for Helicobacter pylori infection with the /sup 13/C-urea test as well as the serological testing. Gastric biopsy was obtained from 36 patients. Patients with proven Helicobacter pylori infection were given treatment for 2 weeks. Six weeks afterwards they were tested again for Helicobacter pylori infection, and their urticaria was clinically assessed. Results: There was no significant difference in the seroprevalence of H. pylori infection between : idiopathic chronic urticaria patients and healthy subjects. Helicobacter pylori was detected in 76% of patients and 69.8% of controls. Out of the 76 patients treated, only 24 showed complete remission of their urticaria after successfully eradicating Helicobacter pylori infection, the others only having some improvement in their symptoms. Conclusion: Patients with idiopathic chronic urticaria have similar high rates of H. pylori infection as healthy subjects. Bacterium eradication is associated with improvement of urticaria symptoms, suggesting a possible role of Helicobacter pylori in the pathogenesis of this skin disorder. (author)

  13. Endogenous interleukin-12 is not required for resolution of Chlamydophila abortus (Chlamydia psittaci serotype 1) infection in mice.

    Science.gov (United States)

    Del Río, L; Buendía, A J; Sánchez, J; Gallego, M C; Caro, M R; Ortega, N; Seva, J; Pallarés, F J; Cuello, F; Salinas, J

    2001-08-01

    A Th1 immune response involving gamma interferon (IFN-gamma) production is required to eliminate Chlamydophila abortus infections. In this study, the role of interleukin-12 (IL-12) in protecting against C. abortus infection was investigated using IL-12(-/-) and wild-type (WT) C57BL/6 mice to determine the role of this Th1-promoting cytokine. IL-12(-/-) mice were able to eliminate the C. abortus infection in a primary infection. However, there was a delay in the clearance of bacteria when IL-12(-/-) mice were infected with a sublethal dose of C. abortus, the delay being associated with a lower production of IFN-gamma. The low level of IFN-gamma was essential for survival of IL-12(-/-) infected mice. Both WT and IL-12(-/-) mice developed a Th1 immune response against C. abortus infection, since they both produced IFN-gamma and immunoglobulin G2a antibody isotype. In addition, when mice were given a secondary infectious challenge with C. abortus, a protective host response which resolved the secondary infection was developed by both WT and IL-12(-/-) mice. The lack of IL-12 resulted in few infiltrating CD4(+) T cells in the liver relative to the number in WT mice, although the number of CD8(+) T cells was slightly higher. The more intense Th1 response presented by WT mice may have a pathogenic effect, as the animals showed higher morbidity after the infection. In conclusion, these results suggest that although IL-12 expedites the clearance of C. abortus infection, this cytokine is not essential for the establishment of a protective host response against the infection.

  14. Petiveria alliacea L. extract protects mice against Listeria monocytogenes infection--effects on bone marrow progenitor cells.

    Science.gov (United States)

    Quadros, M R; Souza Brito, A R; Queiroz, M L

    1999-02-01

    In this study we have investigated the effects of Petiveria alliacea on the hematopoietic response of mice infected with Listeria monocytogenes. Our results demonstrate a protective effect of the crude extract of P. alliacea since the survival of the treated/infected was higher than that in the infected group. Moreover, the number of granulocyte/macrophage colonies (CFU-GM) and the serum colony stimulating activity levels were increased in the treated/infected mice in relation to the infected group. These results suggest an immunomodulation of Petiveria alliacea extract on hematopoiesis, which may be responsible, at least in part, for the increased resistance of mice to Listeria monocytogenes infection.

  15. Effect of Bifidobacterium breve B-3 on skin photoaging induced by chronic UV irradiation in mice.

    Science.gov (United States)

    Satoh, T; Murata, M; Iwabuchi, N; Odamaki, T; Wakabayashi, H; Yamauchi, K; Abe, F; Xiao, J Z

    2015-01-01

    Probiotics have been shown to have a preventative effect on skin photoaging induced by short term UV irradiation, however, the underlying mechanisms and the effect of probiotics on skin photoaging induced by chronic UV irradiation remain unclear. In this study, we investigated the effect of Bifidobacterium breve B-3 on skin photoaging induced by chronic UV irradiation in hairless mice. Mice were irradiated with UVB three times weekly and orally administered B. breve B-3 (2×10(9) cfu/mouse /day) for 7 weeks. Nonirradiated mice and UVB-irradiated mice without probiotic treatment were used as controls. B. breve B-3 significantly suppressed the changes of transepidermal water loss, skin hydration, epidermal thickening and attenuated the damage to the tight junction structure and basement membrane induced by chronic UVB irradiation. Administration of B. breve B-3 tended to suppress the UV-induced interleukin-1β production in skin (P=0.09). These results suggest that B. breve B-3 could potentially be used to prevent photoaging induced by chronic UV irradiation.

  16. Reduced infectivity of waterborne viable but nonculturable Helicobacter pylori strain SS1 in mice.

    Science.gov (United States)

    Boehnke, Kevin F; Eaton, Kathryn A; Fontaine, Clinton; Brewster, Rebecca; Wu, Jianfeng; Eisenberg, Joseph N S; Valdivieso, Manuel; Baker, Laurence H; Xi, Chuanwu

    2017-08-01

    Helicobacter pylori infection has been consistently associated with lack of access to clean water and proper sanitation, but no studies have demonstrated that the transmission of viable but nonculturable (VBNC) H. pylori can occur from drinking contaminated water. In this study, we used a laboratory mouse model to test whether waterborne VBNCH. pylori could cause gastric infection. We performed five mouse experiments to assess the infectivity of VBNCH. pylori in various exposure scenarios. VBNC viability was examined using Live/Dead staining and Biolog phenotype metabolism arrays. High doses of VBNCH. pylori in water were chosen to test the "worst-case" scenario for different periods of time. One experiment also investigated the infectious capabilities of VBNC SS1 using gavage. Further, immunocompromised mice were exposed to examine infectivity among potentially vulnerable groups. After exposure, mice were euthanized and their stomachs were examined for H. pylori infection using culture and PCR methodology. VBNC cells were membrane intact and retained metabolic activity. Mice exposed to VBNCH. pylori via drinking water and gavage were not infected, despite the various exposure scenarios (immunocompromised, high doses) that might have permitted infection with VBNCH. pylori. The positive controls exposed to viable, culturable H. pylori did become infected. While other studies that have used viable, culturable SS1 via gavage or drinking water exposures to successfully infect mice, in our study, waterborne VBNC SS1 failed to colonize mice under all test conditions. Future studies could examine different H. pylori strains in similar exposure scenarios to compare the relative infectivity of the VBNC vs the viable, culturable state, which would help inform future risk assessments of H. pylori in water. © 2017 The Authors. Helicobacter Published by John Wiley & Sons Ltd.

  17. Efficacies of gentamicin-loaded magnetite block ionomer complexes against chronic Brucella melitensis infection

    International Nuclear Information System (INIS)

    Jain-Gupta, Neeta; Pothayee, Nipon; Pothayee, Nikorn; Tyler, Ronald; Caudell, David L.; Balasubramaniam, Sharavanan; Hu, Nan; Davis, Richey M.; Riffle, Judy S.; Sriranganathan, Nammalwar

    2013-01-01

    Anionic copolymers can enable intracellular delivery of cationic drugs which otherwise cannot cross cell membrane barriers. We tested the efficacy of gentamicin-loaded magnetite block ionomer complexes (MBICs) against intracellular Brucella melitensis. Anionic block copolymers were used to coat nanomagnetite through adsorption of a portion of anions on the particle surfaces, then the remaining anions were complexed with 30–32 weight percentage of gentamicin. The zeta potential changed from −39 to −13 mV after encapsulation of the drug with complementary charge. The gentamicin-loaded MBICs had intensity average hydrodynamic diameters of 62 nm, while the polymer-coated nanomagnetite particles without drug were 34 nm in size. No toxicity as measured by a MTS assay was observed upon incubation of the MBICs with J774A.1 murine macrophage-like cells. Confocal microscopic images showed that the MBICs were taken up by the macrophages and distributed in the cell cytoplasm and endosomal/lysosomal compartments. Upon treatment with gentamicin-loaded MBICs (3.5 Log 10 ), B. melitensis-infected macrophages showed significantly higher clearance of Brucella compared to the treatment with free g (0.9 Log 10 ). Compared to doxycycline alone, a combination of doxycycline and gentamicin (either free or encapsulated in MBICs) showed significantly higher clearance of B.melitensis from chronically infected mice. Histopathological examination of kidneys from the MBICs-treated mice revealed multifocal infiltration of macrophages containing intracytoplasmic iron (MBICs) in peri-renal adipose. Although MBICs showed similar efficacy as free gentamicin against Brucella in mice, our strategy presents an effective way to deliver higher loads of drugs intracellularly and ability to study the bio-distribution of drug carriers

  18. Efficacies of gentamicin-loaded magnetite block ionomer complexes against chronic Brucella melitensis infection

    Energy Technology Data Exchange (ETDEWEB)

    Jain-Gupta, Neeta [Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Department of Biomedical Sciences and Pathobiology (United States); Pothayee, Nipon; Pothayee, Nikorn [Virginia Polytechnic Institute and State University, Macromolecules and Interfaces Institute (United States); Tyler, Ronald; Caudell, David L. [Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Department of Biomedical Sciences and Pathobiology (United States); Balasubramaniam, Sharavanan; Hu, Nan; Davis, Richey M.; Riffle, Judy S. [Virginia Polytechnic Institute and State University, Macromolecules and Interfaces Institute (United States); Sriranganathan, Nammalwar, E-mail: nathans@vt.edu [Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Department of Biomedical Sciences and Pathobiology (United States)

    2013-11-15

    Anionic copolymers can enable intracellular delivery of cationic drugs which otherwise cannot cross cell membrane barriers. We tested the efficacy of gentamicin-loaded magnetite block ionomer complexes (MBICs) against intracellular Brucella melitensis. Anionic block copolymers were used to coat nanomagnetite through adsorption of a portion of anions on the particle surfaces, then the remaining anions were complexed with 30–32 weight percentage of gentamicin. The zeta potential changed from −39 to −13 mV after encapsulation of the drug with complementary charge. The gentamicin-loaded MBICs had intensity average hydrodynamic diameters of 62 nm, while the polymer-coated nanomagnetite particles without drug were 34 nm in size. No toxicity as measured by a MTS assay was observed upon incubation of the MBICs with J774A.1 murine macrophage-like cells. Confocal microscopic images showed that the MBICs were taken up by the macrophages and distributed in the cell cytoplasm and endosomal/lysosomal compartments. Upon treatment with gentamicin-loaded MBICs (3.5 Log{sub 10}), B. melitensis-infected macrophages showed significantly higher clearance of Brucella compared to the treatment with free g (0.9 Log{sub 10}). Compared to doxycycline alone, a combination of doxycycline and gentamicin (either free or encapsulated in MBICs) showed significantly higher clearance of B.melitensis from chronically infected mice. Histopathological examination of kidneys from the MBICs-treated mice revealed multifocal infiltration of macrophages containing intracytoplasmic iron (MBICs) in peri-renal adipose. Although MBICs showed similar efficacy as free gentamicin against Brucella in mice, our strategy presents an effective way to deliver higher loads of drugs intracellularly and ability to study the bio-distribution of drug carriers.

  19. Efficacies of gentamicin-loaded magnetite block ionomer complexes against chronic Brucella melitensis infection

    Science.gov (United States)

    Jain-Gupta, Neeta; Pothayee, Nipon; Pothayee, Nikorn; Tyler, Ronald; Caudell, David L.; Balasubramaniam, Sharavanan; Hu, Nan; Davis, Richey M.; Riffle, Judy S.; Sriranganathan, Nammalwar

    2013-11-01

    Anionic copolymers can enable intracellular delivery of cationic drugs which otherwise cannot cross cell membrane barriers. We tested the efficacy of gentamicin-loaded magnetite block ionomer complexes (MBICs) against intracellular Brucella melitensis. Anionic block copolymers were used to coat nanomagnetite through adsorption of a portion of anions on the particle surfaces, then the remaining anions were complexed with 30-32 weight percentage of gentamicin. The zeta potential changed from -39 to -13 mV after encapsulation of the drug with complementary charge. The gentamicin-loaded MBICs had intensity average hydrodynamic diameters of 62 nm, while the polymer-coated nanomagnetite particles without drug were 34 nm in size. No toxicity as measured by a MTS assay was observed upon incubation of the MBICs with J774A.1 murine macrophage-like cells. Confocal microscopic images showed that the MBICs were taken up by the macrophages and distributed in the cell cytoplasm and endosomal/lysosomal compartments. Upon treatment with gentamicin-loaded MBICs (3.5 Log10), B. melitensis-infected macrophages showed significantly higher clearance of Brucella compared to the treatment with free g (0.9 Log10). Compared to doxycycline alone, a combination of doxycycline and gentamicin (either free or encapsulated in MBICs) showed significantly higher clearance of B. melitensis from chronically infected mice. Histopathological examination of kidneys from the MBICs-treated mice revealed multifocal infiltration of macrophages containing intracytoplasmic iron (MBICs) in peri-renal adipose. Although MBICs showed similar efficacy as free gentamicin against Brucella in mice, our strategy presents an effective way to deliver higher loads of drugs intracellularly and ability to study the bio-distribution of drug carriers.

  20. Comorbidities as risk factors of chronic kidney disease in HIV-infected persons

    Directory of Open Access Journals (Sweden)

    Zofia Marchewka

    2015-12-01

    Full Text Available Significant survival prolongation in HIV-infected patients due to effective antiretroviral therapy is connected with increasing prevalence of chronic non-infective diseases in this population, among them chronic kidney disease. The pathogenesis of kidney disease in the setting of HIV includes conditions specific for HIV infection: direct effect of the virus, stage of immunodeficiency and drug toxicity. Chronic comorbidities, such as diabetes mellitus, hypertension, and hyperlipidemia, are additional significant risk factors of kidney disease. In HIV-infected individuals some distinct features of these conditions are observed, which are partly related to the virus and antiretroviral therapy. The article summarizes the effect of comorbidities on kidney function in HIV-infected persons.

  1. Differential lymphocyte and antibody responses in deer mice infected with Sin Nombre hantavirus or Andes hantavirus.

    Science.gov (United States)

    Schountz, Tony; Quackenbush, Sandra; Rovnak, Joel; Haddock, Elaine; Black, William C; Feldmann, Heinz; Prescott, Joseph

    2014-08-01

    Hantavirus cardiopulmonary syndrome (HCPS) is a rodent-borne disease with a high case-fatality rate that is caused by several New World hantaviruses. Each pathogenic hantavirus is naturally hosted by a principal rodent species without conspicuous disease and infection is persistent, perhaps for life. Deer mice (Peromyscus maniculatus) are the natural reservoirs of Sin Nombre virus (SNV), the etiologic agent of most HCPS cases in North America. Deer mice remain infected despite a helper T cell response that leads to high-titer neutralizing antibodies. Deer mice are also susceptible to Andes hantavirus (ANDV), which causes most HCPS cases in South America; however, deer mice clear ANDV. We infected deer mice with SNV or ANDV to identify differences in host responses that might account for this differential outcome. SNV RNA levels were higher in the lungs but not different in the heart, spleen, or kidneys. Most ANDV-infected deer mice had seroconverted 14 days after inoculation, but none of the SNV-infected deer mice had. Examination of lymph node cell antigen recall responses identified elevated immune gene expression in deer mice infected with ANDV and suggested maturation toward a Th2 or T follicular helper phenotype in some ANDV-infected deer mice, including activation of the interleukin 4 (IL-4) pathway in T cells and B cells. These data suggest that the rate of maturation of the immune response is substantially higher and of greater magnitude during ANDV infection, and these differences may account for clearance of ANDV and persistence of SNV. Hantaviruses persistently infect their reservoir rodent hosts without pathology. It is unknown how these viruses evade sterilizing immune responses in the reservoirs. We have determined that infection of the deer mouse with its homologous hantavirus, Sin Nombre virus, results in low levels of immune gene expression in antigen-stimulated lymph node cells and a poor antibody response. However, infection of deer mice with a

  2. Recognition of a 30,000 MW antigen of Giardia muris trophozoites by intestinal IgA from Giardia-infected mice.

    Science.gov (United States)

    Heyworth, M F; Pappo, J

    1990-08-01

    The principal aims of this work were (i) to identify the molecular weight (MW) of Giardia muris trophozoite antigens that are recognized by IgA in small intestinal secretions from G. muris-infected mice, and (ii) to determine whether mouse intestinal Giardia-specific IgA is directed against trophozoite surfaces. BALB/c mice were infected with G. muris cysts, and intestinal secretions were harvested from these mice at various times after the start of Giardia infection, and from uninfected mice. Flow cytometry showed that intestinal IgA from G. muris-infected mice, but not from uninfected mice, became bound to trophozoite surfaces in vitro. Western blotting of trophozoite proteins with mouse intestinal secretions showed that IgA from Giardia-infected mice reacted specifically with a broad protein band of approximately 30,000 MW. This finding suggests that one or more trophozoite proteins of approximately 30,000 MW are targets for intestinal antibody in mice infected with G. muris.

  3. Lovastatin delays infection and increases survival rates in AG129 mice infected with dengue virus serotype 2.

    Directory of Open Access Journals (Sweden)

    Marlen Martinez-Gutierrez

    Full Text Available BACKGROUND: It has been reported that treatment of DENV-infected cultures with Lovastatin (LOV, can affect viral assembly. The objective of this study was to evaluate the effect of LOV on the survival rate and viremia levels of DENV-2-infected AG129 mice. METHODOLOGY/PRINCIPAL FINDINGS: Mice were inoculated with 1 × 10(6 plaque-forming units (PFU/ml of DENV-2 and treated with LOV (200 mg/kg/day. Pre-treatment with one or three doses of LOV increased the survival rate compared to untreated mice (7.3 and 7.1 days, respectively, compared to 4.8 days. Viremia levels also decreased by 21.8% compared to untreated mice, but only in the group administered three doses prior to inoculation. When LOV was administered after viral inoculation, the survival rate increased (7.3 days in the group treated at 24 hpi, 6.8 days in the group treated at 48 hpi and 6.5 days in the group treated with two doses compared to the untreated group (4.8 days. Interestingly, the serum viral titer increased by 24.6% in mice treated at 48 hpi with a single dose of LOV and by 21.7% in mice treated with two doses (at 24 and 48 hpi of LOV compared to untreated mice. Finally histopathological changes in the liver and spleen in infected and untreated mice included massive extramedullary erythropoiesis foci and inflammatory filtration, and these characteristics were decreased or absent in LOV-treated mice. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the effect of LOV on viremia depends on the timing of treatment and on the number of doses administered. We observed a significant increase in the survival rate in both schemes due to a delay in the progression of the disease. However, the results obtained in the post-treatment scheme must be handled carefully because this treatment scheme increases viremia and we do not know how this increase could affect disease progression in humans.

  4. Gene expression-based classifiers identify Staphylococcus aureus infection in mice and humans.

    Directory of Open Access Journals (Sweden)

    Sun Hee Ahn

    Full Text Available Staphylococcus aureus causes a spectrum of human infection. Diagnostic delays and uncertainty lead to treatment delays and inappropriate antibiotic use. A growing literature suggests the host's inflammatory response to the pathogen represents a potential tool to improve upon current diagnostics. The hypothesis of this study is that the host responds differently to S. aureus than to E. coli infection in a quantifiable way, providing a new diagnostic avenue. This study uses Bayesian sparse factor modeling and penalized binary regression to define peripheral blood gene-expression classifiers of murine and human S. aureus infection. The murine-derived classifier distinguished S. aureus infection from healthy controls and Escherichia coli-infected mice across a range of conditions (mouse and bacterial strain, time post infection and was validated in outbred mice (AUC>0.97. A S. aureus classifier derived from a cohort of 94 human subjects distinguished S. aureus blood stream infection (BSI from healthy subjects (AUC 0.99 and E. coli BSI (AUC 0.84. Murine and human responses to S. aureus infection share common biological pathways, allowing the murine model to classify S. aureus BSI in humans (AUC 0.84. Both murine and human S. aureus classifiers were validated in an independent human cohort (AUC 0.95 and 0.92, respectively. The approach described here lends insight into the conserved and disparate pathways utilized by mice and humans in response to these infections. Furthermore, this study advances our understanding of S. aureus infection; the host response to it; and identifies new diagnostic and therapeutic avenues.

  5. Functional memory B cells and long-lived plasma cells are generated after a single Plasmodium chabaudi infection in mice.

    Directory of Open Access Journals (Sweden)

    Francis Maina Ndungu

    2009-12-01

    Full Text Available Antibodies have long been shown to play a critical role in naturally acquired immunity to malaria, but it has been suggested that Plasmodium-specific antibodies in humans may not be long lived. The cellular mechanisms underlying B cell and antibody responses are difficult to study in human infections; therefore, we have investigated the kinetics, duration and characteristics of the Plasmodium-specific memory B cell response in an infection of P. chabaudi in mice. Memory B cells and plasma cells specific for the C-terminal region of Merozoite Surface Protein 1 were detectable for more than eight months following primary infection. Furthermore, a classical memory response comprised predominantly of the T-cell dependent isotypes IgG2c, IgG2b and IgG1 was elicited upon rechallenge with the homologous parasite, confirming the generation of functional memory B cells. Using cyclophosphamide treatment to discriminate between long-lived and short-lived plasma cells, we demonstrated long-lived cells secreting Plasmodium-specific IgG in both bone marrow and in spleens of infected mice. The presence of these long-lived cells was independent of the presence of chronic infection, as removal of parasites with anti-malarial drugs had no impact on their numbers. Thus, in this model of malaria, both functional Plasmodium-specific memory B cells and long-lived plasma cells can be generated, suggesting that defects in generating these cell populations may not be the reason for generating short-lived antibody responses.

  6. Experimental Andes virus infection in deer mice: characteristics of infection and clearance in a heterologous rodent host.

    Directory of Open Access Journals (Sweden)

    Jessica R Spengler

    Full Text Available New World hantaviruses can cause hantavirus cardiopulmonary syndrome with high mortality in humans. Distinct virus species are hosted by specific rodent reservoirs, which also serve as the vectors. Although regional spillover has been documented, it is unknown whether rodent reservoirs are competent for infection by hantaviruses that are geographically separated, and known to have related, but distinct rodent reservoir hosts. We show that Andes virus (ANDV of South America, carried by the long tailed pygmy rice rat (Oligoryzomys longicaudatus, infects and replicates in vitro and in vivo in the deer mouse (Peromyscus maniculatus, the reservoir host of Sin Nombre virus (SNV, found in North America. In experimentally infected deer mice, viral RNA was detected in the blood, lung, heart and spleen, but virus was cleared by 56 days post inoculation (dpi. All of the inoculated deer mice mounted a humoral immune response by 14 dpi, and produced measurable amounts of neutralizing antibodies by 21 dpi. An up-regulation of Ccl3, Ccl4, Ccl5, and Tgfb, a strong CD4⁺ T-cell response, and down-regulation of Il17, Il21 and Il23 occurred during infection. Infection was transient with an absence of clinical signs or histopathological changes. This is the first evidence that ANDV asymptomatically infects, and is immunogenic in deer mice, a non-natural host species of ANDV. Comparing the immune response in this model to that of the immune response in the natural hosts upon infection with their co-adapted hantaviruses may help clarify the mechanisms governing persistent infection in the natural hosts of hantaviruses.

  7. Protein energy malnutrition decreases immunity and increases susceptibility to influenza infection in mice.

    Science.gov (United States)

    Taylor, Andrew K; Cao, Weiping; Vora, Keyur P; De La Cruz, Juan; Shieh, Wun-Ju; Zaki, Sherif R; Katz, Jacqueline M; Sambhara, Suryaprakash; Gangappa, Shivaprakash

    2013-02-01

    Protein energy malnutrition (PEM), a common cause of secondary immune deficiency in children, is associated with an increased risk of infections. Very few studies have addressed the relevance of PEM as a risk factor for influenza. We investigated the influence of PEM on susceptibility to, and immune responses following, influenza virus infection using isocaloric diets providing either adequate protein (AP; 18%) or very low protein (VLP; 2%) in a mouse model. We found that mice maintained on the VLP diet, when compared to mice fed with the AP diet, exhibited more severe disease following influenza infection based on virus persistence, trafficking of inflammatory cell types to the lung tissue, and virus-induced mortality. Furthermore, groups of mice maintained on the VLP diet showed significantly lower virus-specific antibody response and a reduction in influenza nuclear protein-specific CD8(+) T cells compared with mice fed on the AP diet. Importantly, switching diets for the group maintained on the VLP diet to the AP diet improved virus clearance, as well as protective immunity to viral challenge. Our results highlight the impact of protein energy on immunity to influenza infection and suggest that balanced protein energy replenishment may be one strategy to boost immunity against influenza viral infections.

  8. Efficacy of some essential oils in mice infected with Trypanosoma cruzi

    African Journals Online (AJOL)

    Purpose: To evaluate the efficacy of orally administered Cymbopogon citratus, Zingiber officinale and Syzygium aromaticum essential oils (EOs) in mice infected with Trypanosoma cruzi. Methods: Three experiments were conducted with 48 Swiss mice each. The animals were inoculated with 2 x 106 metacyclic ...

  9. Zika Virus Fatally Infects Wild Type Neonatal Mice and Replicates in Central Nervous System

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    Shuxuan Li

    2018-01-01

    Full Text Available Zika virus (ZIKV has been defined as a teratogenic pathogen behind the increased number of cases of microcephaly in French Polynesia, Brazil, Puerto Rico, and other South American countries. Experimental studies using animal models have achieved tremendous insight into understanding the viral pathogenesis, transmission, teratogenic mechanisms, and virus–host interactions. However, the animals used in published investigations are mostly interferon (IFN-compromised, either genetically or via antibody treatment. Herein, we studied ZIKV infection in IFN-competent mice using African (MR766 and Asian strains (PRVABC59 and SZ-WIV01. After testing four different species of mice, we found that BALB/c neonatal mice were resistant to ZIKV infection, that Kunming, ICR and C57BL/6 neonatal mice were fatally susceptible to ZIKV infection, and that the fatality of C57BL/6 neonates from 1 to 3 days old were in a viral dose-dependent manner. The size and weight of the brain were significantly reduced, and the ZIKV-infected mice showed neuronal symptoms such as hind-limb paralysis, tremor, and poor balance during walking. Pathologic and immunofluorescent experiments revealed that ZIKV infected different areas of the central nervous system (CNS including gray matter, hippocampus, cerebral cortex, and spinal cord, but not olfactory bulb. Interestingly, ZIKV replicated in multiple organs and resulted in pathogenesis in liver and testis, implying that ZIKV infection may engender a high health risk in neonates by postnatal infection. In summary, we investigated ZIKV pathogenesis using an animal model that is not IFN-compromised.

  10. Association between Helicobacter pylori Infection and Chronic Urticaria: A Meta-Analysis

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    Huiyuan Gu

    2015-01-01

    Full Text Available Background. Some studies have shown the possible involvement of Helicobacter pylori (H. pylori infection in chronic urticaria, but the relationship remains controversial. The aim of this meta-analysis was to quantitatively assess the association between H. pylori infection and chronic urticaria. Methods. Observational studies comparing the prevalence of H. pylori infection in patients with chronic urticaria and control subjects were identified through a systematic search in MEDLINE and EMBASE up to July 2014. H. pylori infection was confirmed by serological or nonserological tests. For subgroup analyses, studies were separated by region, publication year, and H. pylori detection method to screen the potential factors resulting in heterogeneity. Results. 16 studies involving 965 CU cases and 1235 controls were included. Overall, the prevalence of H. pylori infection was higher in urticarial patients than in controls (OR = 1.66; 95% CI: 1.12–2.45; P=0.01. This result persisted in subanalysis of nine high-quality studies (OR = 1.36; 95% CI: 1.03–1.80; P=0.03. Subgroup analysis showed that detection method of H. pylori is also a potential influential factor for the overall results. Conclusions. Our present meta-analysis suggests that H. pylori infection is significantly, though weakly, associated with an increased risk of chronic urticaria.

  11. Synergistic effects of resveratrol (free and inclusion complex) and sulfamethoxazole-trimetropim treatment on pathology, oxidant/antioxidant status and behavior of mice infected with Toxoplasma gondii.

    Science.gov (United States)

    Bottari, Nathieli B; Baldissera, Matheus D; Tonin, Alexandre A; Rech, Virginia C; Alves, Catiane B; D'Avila, Fernanda; Thomé, Gustavo R; Guarda, Naiara S; Moresco, Rafael N; Camillo, Giovana; Vogel, Fernanda F; Luchese, Cristiane; Schetinger, Maria Rosa C; Morsch, Vera M; Tochetto, Camila; Fighera, Rafael; Nishihira, Vivian S K; Da Silva, Aleksandro S

    2016-06-01

    This study aimed to investigate the synergistic effects of resveratrol and sulfamethoxazole-trimethoprim (ST) on the treatment of mice experimentally infected by Toxoplasma gondii during the chronic phase of the disease considering infection, behavior, and oxidative/antioxidants profile aspects. For the study, 60 mice were initially divided into two groups: uninfected (n = 24) and infected by T. gondii (n = 36). These two groups were later subdivided into other groups and treated with resveratrol (free and inclusion complex containing resveratrol) alone and co-administered with ST: groups A to D were composed by healthy mice and groups E to J were consisted of animals infected by T. gondii (VEG strain). Treatments began 20 days post-infection for 10 consecutive days with oral doses of 0.5 mg kg(-1) of ST (groups B and F), 100 mg kg(-1) of free resveratrol (groups C and G) and inclusion complex of resveratrol (nanoparticles containing resveratrol) (groups D and H), and lastly an co-administration of both drugs (groups I and J). Behavioral tests (memory, anxiety and locomotion) were performed after treatment. Liver and brain fragments were collected to evaluate pathological changes, brain cysts counts, as well as oxidant and antioxidant levels. A reduction on the number of cysts in the brain of animals treated with both drugs combined was observed; there was also reduced number of lesions on both organs. This drug combined effect was also able to reduce oxidative and increase antioxidant levels in infected mice, which might be interpreted as a resveratrol protective effect. In addition, the combination of ST and resveratrol was able to prevent behavioral changes in infected mice. Therefore, the use of co-administration drugs enhances the therapeutic effect acting on a synergic way, reducing the oxidizing effects of the chemical treatment for toxoplasmosis. In addition, resveratrol in inclusion complex when co-administered with ST showed an improved

  12. Alpha-tocopherol transfer protein disruption confers resistance to malarial infection in mice

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    Takeya Motohiro

    2010-04-01

    Full Text Available Abstract Background Various factors impact the severity of malaria, including the nutritional status of the host. Vitamin E, an intra and extracellular anti-oxidant, is one such nutrient whose absence was shown previously to negatively affect Plasmodium development. However, mechanisms of this Plasmodium inhibition, in addition to means by which to exploit this finding as a therapeutic strategy, remain unclear. Methods α-TTP knockout mice were infected with Plasmodium berghei NK65 or Plasmodium yoelii XL-17, parasitaemia, survival rate were monitored. In one part of the experiments mice were fed with a supplemented diet of vitamin E and then infected. In addition, parasite DNA damage was monitored by means of comet assay and 8-OHdG test. Moreover, infected mice were treated with chloroquine and parasitaemia and survival rate were monitored. Results Inhibition of α-tocopherol transfer protein (α-TTP, a determinant of vitamin E concentration in circulation, confers resistance to malarial infection as a result of oxidative damage to the parasites. Furthermore, in combination with the anti-malarial drug chloroquine results were even more dramatic. Conclusion Considering that these knockout mice lack observable negative impacts typical of vitamin E deficiency, these results suggest that inhibition of α-TTP activity in the liver may be a useful strategy in the prevention and treatment of malaria infection. Moreover, a combined strategy of α-TTP inhibition and chloroquine treatment might be effective against drug resistant parasites.

  13. The hepatoprotective activity of blue green algae in Schistosoma mansoni infected mice.

    Science.gov (United States)

    Mohamed, Azza H; Osman, Gamalat Y; Salem, Tarek A; Elmalawany, Alshimaa M

    2014-10-01

    This study aims to evaluate the immunomodulatory effects of a natural product, blue green algae (BGA) (100 mg/kg BW), alone or combined with praziquantel PZQ (250 mg/kg BW) on granulomatous inflammation, liver histopathology, some biochemical and immunological parameters in mice infected with Schistosoma mansoni. Results showed that the diameter and number of egg granuloma were significantly reduced after treatment of S. mansoni-infected mice with BGA, PZQ and their combination. The histopathological alterations observed in the liver of S. mansoni-infected mice were remarkably inhibited after BGA treatments. BGA decreased the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) as well as the level of total protein (TP) while the level of albumin was increased. Treatment of infected mice with BGA, PZQ as well as their combination led to significant elevation in the activities of hepatic antioxidant enzymes glutathione peroxidase (GPX) and glutathione-S-transferase (GST) as compared with control group. Combination of BGA and PZQ resulted in significant reduction in the level of intercellular adhesion molecules-1 (ICAM-1), vascular adhesion molecules-1 (VCAM-1) and tumor necrosis factor-alpha (TNF-α) when compared to those of the S. mansoni-infected group. Overall, BGA significantly inhibited the liver damage accompanied with schistosomiasis, exhibited a potent antioxidant and immunoprotective activities. This study suggests that BGA can be considered as promising for development a complementary and/or alternative medicine against schistosomiasis. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Potential antimalarial activity of Methyl Jasmonate and its effect on lipid profiles in Plasmodium Berghei infected mice.

    Science.gov (United States)

    Oyinloye, Oladapo E; Kosoko, Ayokulehin M; Emikpe, Benjamin; Falade, Catherine O; Ademowo, Olusegun G

    2015-09-01

    The antimalarial activity and lipid profiles of Methyl Jasmonate (MJ) were investigated against established malaria infection in vivo using BALB/c mice. Arteether (AE) and chloroquine (CQ) were used as reference drugs while ethanol was used as the vehicle for drug delivery for MJ. Mice treated with 10 and 25 mg/kg MJ showed a remarkable reduction in percentage parasitemia by 68.3% and 78.2% on day 10(post treatment) respectively while 45.4% and 87.2% reduction in percentage parasitemia were observed in the group treated with 50 mg/kg on day 3 and 10 (post treatment) respectively. The highest mean survival time was observed in CQ followed by AE and MJ in dose-dependent manner. A progressive decrease in packed cell volume (PCV) was observed in infected untreated mice which led to the death of all the mice by day 9 (post treatment). Infected mice treated with MJ showed reduced level of HDL and LDL compared with infected untreated group. As the dose of MJ increased in infected mice cholesterol levels increased while there was reduction in triglyceride. Overall there was marked decrease in parasitemia in Plasmodium berghei infected mice treated with graded doses of MJ but appears to have reduced antimalarial activity compared with CQ and AE.

  15. Cryptosporidium parvum infection in SCID mice infected with only one oocyst: qPCR assessment of parasite replication in tissues and development of digestive cancer.

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    Sadia Benamrouz

    Full Text Available Dexamethasone (Dex treated Severe Combined Immunodeficiency (SCID mice were previously described as developing digestive adenocarcinoma after massive infection with Cryptosporidium parvum as soon as 45 days post-infection (P.I.. We aimed to determine the minimum number of oocysts capable of inducing infection and thereby gastrointestinal tumors in this model. Mice were challenged with calibrated oocyst suspensions containing intended doses of: 1, 10, 100 or 10(5 oocysts of C. parvum Iowa strain. All administered doses were infective for animals but increasing the oocyst challenge lead to an increase in mice infectivity (P = 0.01. Oocyst shedding was detected at 7 days P.I. after inoculation with more than 10 oocysts, and after 15 days in mice challenged with one oocyst. In groups challenged with lower inocula, parasite growth phase was significantly higher (P = 0.005 compared to mice inoculated with higher doses. After 45 days P.I. all groups of mice had a mean of oocyst shedding superior to 10,000 oocyst/g of feces. The most impressive observation of this study was the demonstration that C. parvum-induced digestive adenocarcinoma could be caused by infection with low doses of Cryptosporidium, even with only one oocyst: in mice inoculated with low doses, neoplastic lesions were detected as early as 45 days P.I. both in the stomach and ileo-caecal region, and these lesions could evolve in an invasive adenocarcinoma. These findings show a great amplification effect of parasites in mouse tissues after challenge with low doses as confirmed by quantitative PCR. The ability of C. parvum to infect mice with one oocyst and to develop digestive adenocarcinoma suggests that other mammalian species including humans could be also susceptible to this process, especially when they are severely immunocompromised.

  16. Cryptosporidium parvum infection in SCID mice infected with only one oocyst: qPCR assessment of parasite replication in tissues and development of digestive cancer.

    Science.gov (United States)

    Benamrouz, Sadia; Guyot, Karine; Gazzola, Sophie; Mouray, Anthony; Chassat, Thierry; Delaire, Baptiste; Chabé, Magali; Gosset, Pierre; Viscogliosi, Eric; Dei-Cas, Eduardo; Creusy, Colette; Conseil, Valerie; Certad, Gabriela

    2012-01-01

    Dexamethasone (Dex) treated Severe Combined Immunodeficiency (SCID) mice were previously described as developing digestive adenocarcinoma after massive infection with Cryptosporidium parvum as soon as 45 days post-infection (P.I.). We aimed to determine the minimum number of oocysts capable of inducing infection and thereby gastrointestinal tumors in this model. Mice were challenged with calibrated oocyst suspensions containing intended doses of: 1, 10, 100 or 10(5) oocysts of C. parvum Iowa strain. All administered doses were infective for animals but increasing the oocyst challenge lead to an increase in mice infectivity (P = 0.01). Oocyst shedding was detected at 7 days P.I. after inoculation with more than 10 oocysts, and after 15 days in mice challenged with one oocyst. In groups challenged with lower inocula, parasite growth phase was significantly higher (P = 0.005) compared to mice inoculated with higher doses. After 45 days P.I. all groups of mice had a mean of oocyst shedding superior to 10,000 oocyst/g of feces. The most impressive observation of this study was the demonstration that C. parvum-induced digestive adenocarcinoma could be caused by infection with low doses of Cryptosporidium, even with only one oocyst: in mice inoculated with low doses, neoplastic lesions were detected as early as 45 days P.I. both in the stomach and ileo-caecal region, and these lesions could evolve in an invasive adenocarcinoma. These findings show a great amplification effect of parasites in mouse tissues after challenge with low doses as confirmed by quantitative PCR. The ability of C. parvum to infect mice with one oocyst and to develop digestive adenocarcinoma suggests that other mammalian species including humans could be also susceptible to this process, especially when they are severely immunocompromised.

  17. Cryptosporidiosis and other intestinal parasitic infections in patients with chronic diarrhea.

    Science.gov (United States)

    Mahdi, Nadham K; Ali, Naeel H

    2004-09-01

    To consider the relationship of the parasitic infections including cryptosporidium with chronic diarrhea. Also the effect of chronic disease as pulmonary tuberculosis (TB) and nosocomial infection on the occurrence rate of parasites in cases of chronic diarrhea. Stool samples were collected from 205 patients in teaching, general, child and maternity hospitals in Basrah, Iraq, suffering from chronic diarrhea during 2000. Out of these patients, there were 40 patients with pulmonary TB and 50 inpatients with nosocomial infection. Also 175 apparently healthy individuals who have no episodes of diarrhea for at least 2-months were served as a control group. Direct smear method and then formalin ether sedimentation method were carried out for stool samples to detect intestinal parasites. Fecal smears were prepared from the sediment and stained by the modified Ziehl Neelsen stain for the recovery of red pink oocysts of cryptosporidium. Out of the 205 examined patients, cryptosporidium oocysts were found to be excreted in 20 (9.7%) patients in comparing to 1.1% of the control group. The difference is statistically significant. There were 109 (53.2%) patients found to be positive for intestinal parasitic infections compared to 26 (14.8%) of the control group. The difference is also statistically significant. Out of the 40 TB patients, 2 (5%) were found to excrete cryptosporidium oocysts and also 27 (67.3%) were positive for intestinal parasites. In addition, there were 4 (8%) excreting cryptosporidium oocysts and 23 (46%) infecting by intestinal parasites among the in patients with nosocomial infection. Both acid and non-acid fast parasites should be considered in the differential diagnosis of undiagnosed chronic diarrhea especially among patients with pulmonary TB or nosocomial infection.

  18. Behavioural alterations are independent of sickness behaviour in chronic experimental Chagas disease.

    Science.gov (United States)

    Vilar-Pereira, Glaucia; Ruivo, Leonardo Alexandre de Souza; Lannes-Vieira, Joseli

    2015-12-01

    The existence of the nervous form of Chagas disease is a matter of discussion since Carlos Chagas described neurological disorders, learning and behavioural alterations in Trypanosoma cruzi-infected individuals. In most patients, the clinical manifestations of the acute phase, including neurological abnormalities, resolve spontaneously without apparent consequence in the chronic phase of infection. However, chronic Chagas disease patients have behavioural changes such as psychomotor alterations, attention and memory deficits, and depression. In the present study, we tested whether or not behavioural alterations are reproducible in experimental models. We show that C57BL/6 mice chronically infected with the Colombian strain of T. cruzi (150 days post-infection) exhibit behavioural changes as (i) depression in the tail suspension and forced swim tests, (ii) anxiety analysed by elevated plus maze and open field test sand and (iii) motor coordination in the rotarod test. These alterations are neither associated with neuromuscular disorders assessed by the grip strength test nor with sickness behaviour analysed by temperature variation sand weight loss. Therefore, chronically T. cruzi-infected mice replicate behavioural alterations (depression and anxiety) detected in Chagas disease patients opening an opportunity to study the interconnection and the physiopathology of these two biological processes in an infectious scenario.

  19. Phenotypes selected during chronic lung infection in cystic fibrosis patients

    DEFF Research Database (Denmark)

    Ciofu, Oana; Mandsberg, Lotte F; Wang, Hengzhuang

    2012-01-01

    During chronic lung infection of patients with cystic fibrosis, Pseudomonas aeruginosa can survive for long periods of time under the challenging selective pressure imposed by the immune system and antibiotic treatment as a result of its biofilm mode of growth and adaptive evolution mediated by g...... the importance of biofilm prevention strategies by early aggressive antibiotic prophylaxis or therapy before phenotypic diversification during chronic lung infection of patients with cystic fibrosis....

  20. Evaluation of Protective Immune Responses Induced by Recombinant TrxLp and ENO2 Proteins against Toxoplasma gondii Infection in BALB/c Mice

    Directory of Open Access Journals (Sweden)

    Meng Wang

    2016-01-01

    Full Text Available Toxoplasma gondii is an obligate intracellular parasitic protozoan that can infect almost all species of warm-blooded animals. As any chemical-based drugs could not act against the tissue cyst stage of T. gondii, vaccination may be one of the ideal control strategies. In the present study, two new vaccine candidates, named TgENO2 and TgTrxLp, were purified from Escherichia coli with pET-30a(+ expression system and then were injected into BALB/c mice to evaluate the protective efficacy against acute and chronic toxoplasmosis. The results showed that both the recombinant proteins, either alone or in combination, could elicit strong humoral and cellular immune responses with a higher level of IgG antibodies, IFN-γ, IL-2, CD4+, and CD8+ T cells as compared to those in mice from control groups. After acute challenge with tachyzoites of the GJS strain, mice immunized with rTgTrxLp (8±2.77 d, rTgENO2 (7.4±1.81 d, and rTgTrxLp + rTgENO2 (8.38±4.57 d proteins showed significantly longer survival time than those that received Freund’s adjuvant (6.78±2.08 d and PBS (6.38±4.65 d (χ2 = 9.687, df = 4, P=0.046. The protective immunity of rTgTrxLp, rTgENO2, and rTgTrxLp + rTgENO2 proteins against chronic T. gondii infection showed 69.77%, 58.14%, and 20.93% brain cyst reduction as compared to mice that received PBS. The present study suggested that both TgENO2 and TgTrxLp were potential candidates for the development of multicomponent vaccines against toxoplasmosis.

  1. Immunomodulatory and protective effect of probiotic Lactobacillus casei against Candida albicans infection in malnourished mice.

    Science.gov (United States)

    Villena, Julio; Salva, Susana; Agüero, Graciela; Alvarez, Susana

    2011-06-01

    The effect of Lactobacillus casei CRL 431 (Lc), when administered as a supplement to a repletion diet, on the resistance of malnourished mice to Candida albicans infection was studied. Weaned mice were malnourished by being given a protein-free diet (PFD) for 21 days. The malnourished mice were then fed a balanced conventional diet (BCD) for 7 days or BCD for 7 days with supplemental Lc on days 6 and 7 (BCD+Lc). Malnourished (MNC) and well-nourished (WNC) mice were used as controls. At the end of the treatments the mice were infected intraperitoneally with C. albicans. Animals that had received probiotics had improved survival and resistance against this infection compared to those in the BCD and MNC groups. The number and fungicidal activity of phagocytes, and the concentrations of tumor necrosis factor-α, interferon-γ and interleukin-6 (IL-6), increased in blood and infected tissues in all experimental groups, but MNC mice showed lower concentrations than those in the WNC group. BCD and BCD+Lc mice showed higher concentrations of these variables than those in the MNC group, but only the BCD+Lc group presented values similar to the WNC mice. Malnutrition also impaired the production of IL-17 and IL-10 in response to infection. Both repletion treatments normalized IL-17 concentrations, but IL-10 in the BCD+Lc group was significantly higher than in WNC mice. The addition of L. casei to the repletion diet normalized the immune response against C. albicans, allowing efficient recruitment and activation of phagocytes, as well as effective release of pro-inflammatory cytokines. In addition, probiotic treatment induced an increase in IL-10 concentrations, which would have helped to prevent damage caused by the inflammatory response. © 2011 The Societies and Blackwell Publishing Asia Pty Ltd.

  2. Lycorine reduces mortality of human enterovirus 71-infected mice by inhibiting virus replication

    Directory of Open Access Journals (Sweden)

    Qin Chuan

    2011-10-01

    Full Text Available Abstract Human enterovirus 71 (EV71 infection causes hand, foot and mouth disease in children under 6 years old and this infection occasionally induces severe neurological complications. No vaccines or drugs are clinical available to control EV71 epidemics. In present study, we show that treatment with lycorine reduced the viral cytopathic effect (CPE on rhabdomyosarcoma (RD cells by inhibiting virus replication. Analysis of this inhibitory effect of lycorine on viral proteins synthesis suggests that lycorine blocks the elongation of the viral polyprotein during translation. Lycorine treatment of mice challenged with a lethal dose of EV71 resulted in reduction of mortality, clinical scores and pathological changes in the muscles of mice, which were achieved through inhibition of viral replication. When mice were infected with a moderate dose of EV71, lycorine treatment was able to protect them from paralysis. Lycorine may be a potential drug candidate for the clinical treatment of EV71-infected patients.

  3. Excess Fibrin Deposits Decrease Fetal Weight of Pregnant Mice Infected by Plasmodium berghei

    Directory of Open Access Journals (Sweden)

    Desy Andari

    2014-05-01

    Full Text Available Low birth weight is commonly attributed to malaria in pregnancy, but the cellular and molecular mechanisms that underlie this poor birth outcome are incompletely understood. A universally described histopathological feature of placental malaria is excessive deposition of fibrin, the end-product of the coagulation cascade. This study was conducted to compare fibrin deposit in pregnant mice that infected by Plasmodium berghei (treatment group to the normal pregnant mice (control group and its association with fetal weight. This research is in vivo experimental laboratory study that used 18 pregnant Balb/c mice which divided to the control the group (8 mice and treatment group (9 mice infected by P.berghei. Placentas were staining with Haematoxylin-Eosin (HE for fibrin deposits examination whereas fetal weight was performed with Mettler analytical balance AE 50. Fetal weight of the treatment group was lower than those of the control group (t test, p=0,002. Fibrin deposits were increased in the treatment group (t test, p=0,005 and influenced weight of fetuses (Spearman r= -0,586, p= 0,014. Weights of fetuses are interfered by fibrin deposits during malaria infection.

  4. The role of CD80/CD86 in generation and maintenance of functional virus-specific CD8+ T cells in mice infected with lymphocytic choriomeningitis virus

    DEFF Research Database (Denmark)

    Grujic, Mirjana; Bartholdy, Christina; Remy, Melissa

    2010-01-01

    Lymphocytic choriomeningitis virus (LCMV)-specific CD8(+) T cell responses are considered to be independent of CD28-B7 costimulation. However, the LCMV-specific response has never been evaluated in B7.1/B7.2(-/-) mice. For this reason, we decided to study the T cell response in B7.1/B7.2(-/-) mice......, but no chronic infection. Taken together, these results indicate that B7 costimulation is required for induction and maintenance of LCMV-specific CD8(+) T cell memory, irrespective of the LCMV strain used for priming. However, the erosion of CD8(+) T cell memory in B7.1/B7.2(-/-) mice was more pronounced...

  5. The curative activity of thioridazine on mice infected with Mycobacterium tuberculosis

    DEFF Research Database (Denmark)

    Martins, Marta; Viveiros, Miguel; Kristiansen, Jette E

    2007-01-01

    BACKGROUND: The aim of the study was to evaluate the effectiveness of thioridazine (TZ) at different dose levels on mice that had been infected intraperitoneally (i.p.) with a high dose of the Mycobacterium tuberculosis ATCC H37Rv strain. SUBJECTS AND METHODS: Groups of five female BALB/C mice were...

  6. Nitric oxide and HSV vaginal infection in BALB/c mice

    International Nuclear Information System (INIS)

    Benencia, Fabian; Gamba, Gisela; Cavalieri, Hernan; Courreges, Maria Cecilia; Benedetti, Ruben; Villamil, Soledad Maria; Massouh, Ernesto Jorge

    2003-01-01

    Here we study the role of nitric oxide in the vaginal infection of Balb/c mice with herpes simplex virus type 2. Inducible nitric oxide synthase (iNOS) mRNA was detected by RT-PCR in vaginal tissue and inguinal lymph nodes early postinfection. iNOS was also found to be activated in cells recovered from vaginal washings of infected animals. Animals treated with aminoguanidine (AG), an iNOS inhibitor, showed a dose-dependent increase in vaginal pathology after viral infection compared to controls. Viral titers in vaginal washings and vaginas were higher in AG-treated mice. Treated animals presented higher PMN counts in vaginal washings compared to controls. Histopathology studies revealed a profound inflammatory exudate in vaginal tissue of treated animals. Finally, RT-PCR analysis showed increased expression of the chemokines MIP-2 and RANTES in vaginal tissue and inguinal lymph nodes of these animals

  7. Pathophysiology of chronic pancreatitis induced by dibutyltin dichloride joint ethanol in mice.

    Science.gov (United States)

    Zhang, Hong; Liu, Bin; Xu, Xiao-Fan; Jiang, Ting-Ting; Zhang, Xiao-Qin; Shi, Ying-Li; Chen, Yu; Liu, Fang; Gu, Jie; Zhu, Lin-Jia; Wu, Nan

    2016-03-14

    To search for a new chronic pancreatitis model in mice suitable for investigating the pathophysiological processes leading to pancreatic fibrosis. The mice were randomly divided into 2 groups (n = 50), control group and model group. The mice in model group were given ethanol (10%) in drinking water after injection of dibutyltin dichloride (DBTC) (8 mg/kg BW) in tail vein. The mice in control group were injected with only solvent into tail vein (60% ethanol, 20% glycerine and 20% normal saline) and drank common water. At days 1, 7, 14, 28, and 56 after application of DBTC or solvent, 10 mice in one group were killed at each time point respectively. Blood was obtained by inferior vena cava puncture. The activity of amylase, concentration of bilirubin and hyaluronic acid in serum were assayed. The pancreas was taken to observe the pancreatic morphology by HE staining, and to characterize the pancreatic fibrosis by Masson staining. The expression of F4/80, CD3 and fibronectin (FN) were assayed by immuno-histochemistry or Immunofluorescence technique. Collagen type I (COL1A1) in pancreas were detected by Western blot. The expression of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA in the pancreas was assessed by real time PCR. DBTC induced an acute edematous pancreatitis within 1 d. The dilated acini, scattered acinar cell necrosis, and inflammatory cells were found at day 7. Extensive infiltration with inflammatory cells following deposition of connective tissue was observed at day 14. At day 28, level of pancreatic fibrosis was aggravated. The pancreatic tissue was replaced by an extended interstitial fibrosis at the end of 2 mo. There was significant difference in the level of amylase, bilirubin and hyaluronic acid in serum between control group and model group (P chronic pancreatitis in accordance with the pathophysiological modification of human. DBTC joint Ethanol-induced pancreatitis in mice is an effective and

  8. Congenital Toxoplasmosis in Chronically Infected and Subsequently Challenged Ewes.

    Science.gov (United States)

    Dos Santos, Thaís Rabelo; Faria, Gabriela da Silva Magalhães; Guerreiro, Bruna Martins; Dal Pietro, Nathalia Helena Pereira da Silva; Lopes, Welber Daniel Zanetti; da Silva, Helenara Machado; Garcia, João Luis; Luvizotto, Maria Cecília Rui; Bresciani, Katia Denise Saraiva; da Costa, Alvimar José

    2016-01-01

    This experiment studied congenital transmission in sheep experimentally infected with oocysts of Toxoplasma gondii and reinfected at one of three stages of pregnancy. Twenty ewes were experimentally infected with T. gondii strain ME49 (day 0). After the T. gondii infection became chronic (IFAT≤512), the ewes were allocated with rams for coverage. After the diagnosis of pregnancy, these ewes were allocated into four experimental groups (n = 5): I-reinfected with T. gondii on the 40th day of gestation (DG); II-reinfected on DG 80; III-reinfected on DG 120; and IV-saline solution on DG 120 (not reinfected). Five ewes (IFATewes produced lambs serologically positive for T. gondii. The results of the mouse bioassay, immunohistochemistry and PCR assays revealed the presence of T. gondii in all 20 sheep and their lambs. The congenital transmission of T. gondii was associated with fetal loss and abnormalities in persistently infected sheep and in ewes infected and subsequently reinfected by this protozoan. Therefore, congenital T. gondii infection was common when ewes were chronically infected prior to pregnancy, with or without reinfection during at various stages of gestation.

  9. Chronic Infections of the Urinary Tract and Bladder Cancer Risk: a Systematic Review.

    Science.gov (United States)

    Anderson-Otunu, Oghenetejiri; Akhtar, Saeed

    2016-01-01

    Literature on the relationship between recurrent urinary tract infections and urinary bladder carcinoma risk has been inconsistent. Therefore, we carried out this systematic review of observational studies to ascertain if there is any association between chronic urinary tract infection and urinary bladder carcinoma. A total of 10 databases were searched using Boolean: CINAHL, PUBMED, Google Scholar, Medline, Science Direct, SCIRUS, Cochrane, UK PubMed central, NHS evidence and WHO-website. The search yielded an initial hit of 3,518 articles and after screening and critical appraisal, seven studies were included for this review. Four articles reported an association between chronic urinary tract infections and bladder cancer while three concluded a weak or no association at least in one gender. Main findings in this review were that most of the studies reported an association between chronic urinary tract infections and bladder cancer risk. However, inferences about the causal association between chronic urinary tract infections and bladder cancer risk should be drawn cautiously considering the methodological limitations of case-control studies included in this review. Therefore, more empirical evidence is needed to determine the causal nature of relationships between chronic urinary tract infections and bladder cancer risk.

  10. Altered energy balance and cytokine gene expression in a murine model of chronic infection with Toxoplasma gondii.

    Science.gov (United States)

    Arsenijevic, D; Girardier, L; Seydoux, J; Chang, H R; Dulloo, A G

    1997-05-01

    The temporal pattern of changes in energy balance and cytokine mRNA expression in spleen and brain were examined in a mouse model of infection with Toxoplasma gondii. During days 1-7 postinfection, food intake was unaltered, but energy expenditure was significantly increased, and this was associated with elevated tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1, IL-5, and interferon (IFN)-gamma. The hypermetabolic state persisted during subsequent anorexia, whose onset coincided with elevated IL-2, and at the end of the acute phase of cachexia, the dual anorexic and hypermetabolic states were associated with the cytokines examined: TNF-alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, and IFN-gamma. In the chronic phase of the infection, the mice showed either partial weight recovery (gainers) or no weight regain (nongainers). The infected gainers, though still hypophagic, were no longer hypermetabolic, and their cytokine mRNA was no longer elevated, except for TNF-alpha and IL-10. In contrast, the infected nongainers continued to show both anoroxia and hypermetabolism, which were associated with elevations in all cytokines examined and particularly those of the TH2 profile (IL-4 and IL-5) and IL-6. Taken together, these studies reveal a distinct pattern of cytokine mRNA expression underlying 1) hypermetabolism vs. anorexia, 2) acute vs. chronic cachexia, and 3) stable weight loss vs. partial weight recovery.

  11. The use of protein hydrolysate improves the protein intestinal absorption in undernourished mice infected with Schistosoma mansoni

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    Coutinho Eridan M.

    2002-01-01

    Full Text Available Patients residing in endemic areas for schistosomiasis in Brazil are usually undernourished and when they develop the hepatosplenic clinical form of the disease should usually receive hospital care, many of them being in need of nutritional rehabilitation before specific treatment can be undertaken. In the mouse model, investigations carried out in our laboratory detected a reduced aminoacid uptake in undernourished animals which is aggravated by a superimposed infection with Schistosoma mansoni. However, in well-nourished infected mice no dysfunction occurs. In this study, we tried to improve the absorptive intestinal performance of undernourished mice infected with S. mansoni by feeding them with hydrolysed casein instead of whole casein. The values obtained for the coefficient of protein intestinal absorption (cpia among well-nourished mice were above 90% (either hydrolysed or whole protein. In undernourished infected mice, however, the cpia improved significantly after feeding them with hydrolysed casein, animals reaching values close to those obtained in well-nourished infected mice.

  12. Transcriptional Profiling of Immune-Related Genes in Leishmania infantum-Infected Mice: Identification of Potential Biomarkers of Infection and Progression of Disease

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    Eduardo Ontoria

    2018-06-01

    Full Text Available Leishmania spp. is a protozoan parasite that affects millions of people around the world. At present, there is no effective vaccine to prevent leishmaniases in humans. A major limitation in vaccine development is the lack of precise understanding of the particular immunological mechanisms that allow parasite survival in the host. The parasite-host cell interaction induces dramatic changes in transcriptome patterns in both organisms, therefore, a detailed analysis of gene expression in infected tissues will contribute to the evaluation of drug and vaccine candidates, the identification of potential biomarkers, and the understanding of the immunological pathways that lead to protection or progression of disease. In this large-scale analysis, differential expression of 112 immune-related genes has been analyzed using high-throughput qPCR in spleens of infected and naïve Balb/c mice at four different time points. This analysis revealed that early response against Leishmania infection is characterized by the upregulation of Th1 markers and M1-macrophage activation molecules such as Ifng, Stat1, Cxcl9, Cxcl10, Ccr5, Cxcr3, Xcl1, and Ccl3. This activation doesn't protect spleen from infection, since parasitic burden rises along time. This marked difference in gene expression between infected and control mice disappears during intermediate stages of infection, probably related to the strong anti-inflammatory and immunosuppresory signals that are activated early upon infection (Ctla4 or remain activated throughout the experiment (Il18bp. The overexpression of these Th1/M1 markers is restored later in the chronic phase (8 wpi, suggesting the generation of a classical “protective response” against leishmaniasis. Nonetheless, the parasitic burden rockets at this timepoint. This apparent contradiction can be explained by the generation of a regulatory immune response characterized by overexpression of Ifng, Tnfa, Il10, and downregulation Il4 that

  13. Methyl gallate limits infection in mice challenged with Brucella abortus while enhancing the inflammatory response.

    Science.gov (United States)

    Reyes, A W B; Kim, D G; Simborio, H L T; Hop, H T; Arayan, L T; Min, W; Lee, J J; Chang, H H; Kim, S

    2016-03-01

    To investigate the effects of methyl gallate (MG) on murine macrophages, cytokine production and treatment of Brucella abortus infection using a mouse model. MG-treated cells displayed increased F-actin polymerization and modest increase in ERK, JNK and p38α phosphorylation levels. The mice were intraperitoneally infected with Br. abortus and were orally treated with PBS or MG for 14 days. The weight and bacterial number from each spleen were monitored, and the serum was evaluated for cytokine production. The spleen proliferation and bacterial burden were lower in the MG-treated group than in the MG-untreated control. The noninfected MG-treated mice displayed increased production of TNF, IFN-γ, and the chemokine MCP-1, whereas the Br. abortus-infected MG-treated mice revealed enhanced induction of IL-12p70, TNF and IL-10 compared to the MG-untreated control. MG induced F-actin polymerization and modest upregulation of MAPKs. Furthermore, oral treatment with MG induced an immune response and decreased bacterial proliferation in Br. abortus-infected mice, suggesting that MG may be an alternative treatment for brucellosis. The present study demonstrates the therapeutic effects of MG against Brucella infection through induction of cytokine production and protection from bacterial proliferation in the spleens of mice. © 2015 The Society for Applied Microbiology.

  14. Chronic High Fat Diet Consumption Impairs Metabolic Health of Male Mice.

    Science.gov (United States)

    Morselli, Eugenia; Criollo, Alfredo; Rodriguez-Navas, Carlos; Clegg, Deborah J

    We show that chronic high fat diet (HFD) feeding affects the hypothalamus of male but not female mice. In our study we demonstrate that palmitic acid and sphingolipids accumulate in the central nervous system of HFD-fed males. Additionally, we show that HFD-feeding reduces proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) thus reducing estrogen receptor α (ERα) and driving hypothalamic inflammation in male but not female mice. Hypothalamic inflammation correlates with markers of metabolic dysregulation as indicated by dysregulation in glucose intolerance and myocardial function. Lastly, we demonstrate that there are blockages in mitophagy and lipophagy in hypothalamic tissues in males. Our data suggest there is a sexually dimorphic response to chronic HDF exposure, females; despite gaining the same amount of body weight following HFD-feeding, appear to be protected from the adverse metabolic effects of the HFD.

  15. Abnormal neural activation patterns underlying working memory impairment in chronic phencyclidine-treated mice.

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    Yosefu Arime

    Full Text Available Working memory impairment is a hallmark feature of schizophrenia and is thought be caused by dysfunctions in the prefrontal cortex (PFC and associated brain regions. However, the neural circuit anomalies underlying this impairment are poorly understood. The aim of this study is to assess working memory performance in the chronic phencyclidine (PCP mouse model of schizophrenia, and to identify the neural substrates of working memory. To address this issue, we conducted the following experiments for mice after withdrawal from chronic administration (14 days of either saline or PCP (10 mg/kg: (1 a discrete paired-trial variable-delay task in T-maze to assess working memory, and (2 brain-wide c-Fos mapping to identify activated brain regions relevant to this task performance either 90 min or 0 min after the completion of the task, with each time point examined under working memory effort and basal conditions. Correct responses in the test phase of the task were significantly reduced across delays (5, 15, and 30 s in chronic PCP-treated mice compared with chronic saline-treated controls, suggesting delay-independent impairments in working memory in the PCP group. In layer 2-3 of the prelimbic cortex, the number of working memory effort-elicited c-Fos+ cells was significantly higher in the chronic PCP group than in the chronic saline group. The main effect of working memory effort relative to basal conditions was to induce significantly increased c-Fos+ cells in the other layers of prelimbic cortex and the anterior cingulate and infralimbic cortex regardless of the different chronic regimens. Conversely, this working memory effort had a negative effect (fewer c-Fos+ cells in the ventral hippocampus. These results shed light on some putative neural networks relevant to working memory impairments in mice chronically treated with PCP, and emphasize the importance of the layer 2-3 of the prelimbic cortex of the PFC.

  16. Effect of infection by irradiated Trichinella Spirals larvae on mice and assessment the role of Al bendazole in treating them

    International Nuclear Information System (INIS)

    Moawad, M.A.F.; Amin, M.M.

    2005-01-01

    The present study was carried out to investigate the effect of infection with irradiated Trichinella Spiralis larvae on mice and to asses the role of albendazole in treating them. This study included parasitological and histopathological studies on mice infected with irradiated Trichinella Spiralis larvae in comparison with mice infected with non-irradiated Trichinella Spiralis only or with mice treated after infection by albendazole. The obtained data revealed that, in mice infected with irradiated Trichinella Spiralis larvae (50 Krad or 80 Krad), the number and length of worms in the small intestine, as well as, the number of encysted larvae in muscles of mice, especially diaphragm and tongue, were significantly decreased. Also, using al bendazole 24 hours after infection with irradiated larvae lead to high significant decrease in all the previously mentioned parameters

  17. Protein 3-nitrotyrosine formation during Trypanosoma cruzi infection in mice

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    M. Naviliat

    2005-12-01

    Full Text Available Nitric oxide (·NO is a diffusible messenger implicated in Trypanosoma cruzi resistance. Excess production of ·NO and oxidants leads to the generation of nitrogen dioxide (·NO2, a strong nitrating agent. Tyrosine nitration is a post-translational modification resulting from the addition of a nitro (-NO2 group to the ortho-position of tyrosine residues. Detection of protein 3-nitrotyrosine is regarded as a marker of nitro-oxidative stress and is observed in inflammatory processes. The formation and role of nitrating species in the control and myocardiopathy of T. cruzi infection remain to be studied. We investigated the levels of ·NO and protein 3-nitrotyrosine in the plasma of C3H and BALB/c mice and pharmacologically modulated their production during the acute phase of T. cruzi infection. We also looked for protein 3-nitrotyrosine in the hearts of infected animals. Our results demonstrated that C3H animals produced higher amounts of ·NO than BALB/c mice, but their generation of peroxynitrite was not proportionally enhanced and they had higher parasitemias. While N G-nitro-arginine methyl ester treatment abolished ·NO production and drastically augmented the parasitism, mercaptoethylguanidine and guanido-ethyl disulfide, at doses that moderately reduced the ·NO and 3-nitrotyrosine levels, paradoxically diminished the parasitemia in both strains. Nitrated proteins were also demonstrated in myocardial cells of infected mice. These data suggest that the control of T. cruzi infection depends not only on the capacity to produce ·NO, but also on its metabolic fate, including the generation of nitrating species that may constitute an important element in parasite resistance and collateral myocardial damage.

  18. Delayed-type hypersensitivity to Babesia microti-infected erythrocytes in mice

    International Nuclear Information System (INIS)

    Ruebush, M.J.; Troutman, E.H.; Kennedy, D.A.

    1986-01-01

    Strong delayed-type hypersensitivity (DTH) to Babesia microti was elicited when intraerythrocytic parasites (IEP) were inoculated subcutaneously into the flank of normal mice 6 to 14 days before challenge in the ipsilateral footpad with 10(8) IEP. Intraperitoneal or intravenous administration of antigen did not sensitize mice for DTH. When challenge was given 21 days after immunization, the response was approximately half of the maximum and then rose again slowly over the next 3 weeks to levels that were not significantly different from those maximal values. The response was classified as a true DTH reaction on the basis of kinetics, histology, and the transfer of responsiveness with immune T lymphocytes of the Ly 1+ phenotype, but not with serum. The reaction was specific for IEP since control groups given two injections of red blood cells from uninfected syngeneic mice (NRBC) or one injection of NRBC or sheep red blood cells (SRBC) and one of IEP never developed significant footpad swelling. Freed parasites obtained by osmotic rupture, density gradient sedimentation, and lethally irradiated IEP were also effective for elicitation of DTH. Anti-IEP DTH was expressed in a dose-dependent fashion with 10(6), 10(7), or 10(8) parasites sufficing for immunizing inoculum as long as 10(8) parasites were used as the challenge dose. Mice immunized and challenged with 10(8) lethally irradiated IEP (60 krad, 60Co), were protected against subsequent intraperitoneal challenge with 10(8) viable IEP. If mice were infected intraperitoneally with 10(8) IEP at any time between 21 days before immunization to 2 hr after challenge, their ability to respond to immunization and challenge was profoundly depressed. Development of a strong anti-parasite DTH response can occur in parallel with resistance to infection, but is not a rapid sequela of bloodborne infection

  19. Chronic exposure to trichloroethene causes early onset of SLE-like disease in female MRL +/+ mice

    International Nuclear Information System (INIS)

    Cai Ping; Koenig, Rolf; Boor, Paul J.; Kondraganti, Shakuntala; Kaphalia, Bhupendra S.; Khan, M. Firoze; Ansari, G.A.S.

    2008-01-01

    Trichloroethene (TCE) exacerbates the development of autoimmune responses in autoimmune-prone MRL +/+ mice. Although TCE-mediated autoimmune responses are associated with an increase in serum immunoglobulins and autoantibodies, the underlying mechanism of autoimmunity is not known. To determine the progression of TCE-mediated immunotoxicity, female MRL +/+ mice were chronically exposed to TCE through the drinking water (0.5 mg/ml of TCE) for various periods of time. Serum concentrations of antinuclear antibodies increased after 36 and 48 weeks of TCE exposure. Histopathological analyses showed lymphocyte infiltration in the livers of MRL +/+ mice exposed to TCE for 36 or 48 weeks. Lymphocyte infiltration was also apparent in the pancreas, lungs, and kidneys of mice exposed to TCE for 48 weeks. Immunoglobulin deposits in kidney glomeruli were found after 48 weeks of exposure to TCE. Our results suggest that chronic exposure to TCE promotes inflammation in the liver, pancreas, lungs, and kidneys, which may lead to SLE-like disease in MRL +/+ mice

  20. Congenital and nursing effects on the evolution of Schistosoma mansoni infection in mice

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    J. A. Lenzi

    1987-01-01

    Full Text Available Modification of the immune response to schistosomal infection in children or offspring born to mother R infected with Schistosoma mansoni has been demonstrated in human and in experimental schistosomiasis. One of the hypothesis to explain this fact could be the transfer of circulating antigens and antibodies from mother to foetus through the placenta or from mother to child by milk. The results of this spontaneous transference are controversial in the literature. In an attempt to investigate these questions, we studied one hundred and twenty offspring (Swiss mice, sixty born to infected-mothers (group A and sixty born to non-infected mothers (group B. These were percutaneously infected with 50 cercariae/mouse, and divided in six sub-groups (20 mice/sub-group, according to the following schedule: after birth (sub-groups A.I and B.I, 10 days old (sub-groups A.II and B.II and 21 days old (sub-groups A.III and B.III. After the exposure period, the young mice returned to their own mothers for nursing. Six weeks later, the mice were killed. We obtained the following results: 1 There is transference of antibody to cercariae (CAP, adult worms (SWAP and egg antigens (SEA from the infected mothers to the offspring, probably through placenta and milk; 2 Offspring born to infected mothers exhibit much less coagulative hepatic necrosis and show a lower number of eggs in the small intestine and a less intense and predominant exsudative stage of the hepatic granulomas when compared with the exsudative-productive stage of the control groups. The findings suggest that congenital and nursing factors can interfere on the development of the schistosomiasis infection, causing an hyporesponse to the eggs.

  1. Suppression of humoral response during the course of Candida albicans infection in mice.

    Science.gov (United States)

    Valdez, J C; Meson, O E; de Valdez, G A; Sirena, A

    1984-10-30

    This paper aims at demonstrating the non-specific immunosuppression as regards thyme-dependent antigens sheep erythrocytes (SRBC) during the course of Candida albicans systemic infection. Three lots of syngeneic/BALB/c mice, 8-12 weeks of age, were used. The first normal lot was inoculated via the intraperitoneal route with a (SRBC) suspension (4 X 10(8) cells ml) in a Hank's balanced saline solution. The primary response of antibodies formed by splenic cells was measured from 4 to 8 days after inoculation using the direct plaque forming cells technique. The second lot was infected by the same route with a suspension of Candida albicans (1 X 10(7) cells). Positive retrocultures from the blood and kidneys of these infected mice were obtained. These yeasts cultivated in a Sabouraud medium were harvested after 20 h at 37 degrees C. Following the same methodology the immune response to SRBC was determined. The serum obtained from infected mice was transferred to a third lot of mice at different intervals during the course of the infection. The immune response to SRBC was done by the direct plaque-forming cells technique. Controls were carried out using normal donors and recipients. A suppression of the immune response was obtained as from the 2nd day of inoculation up to the 28th day. It was not possible to transfer such suppression passively by means of the serum. These results suggest that the systemic infection by Candida albicans induce a non-specific immunosuppression in the organism, already demonstrated in viral infections, bacteria, protozoaria and metazoaria in mammals. In some way, this will contribute to explain the mechanisms of immune response to Candida albicans.

  2. PREVALENCE OF MALNUTRITION IN CHILDREN WITH CHRONIC HEPATITIS B INFECTION.

    Science.gov (United States)

    Şahin, Yasin

    2016-01-01

    There have been limited studies investigating the impact of chronic hepatitis B virus infection on the growth of children. Our objective was to investigate the prevalence of malnutrition in children with chronic hepatitis B infection. The nutritional status of patients was retrospectively evaluated in the outpatient Clinic of Pediatric Gastroenterology between February and November 2014. During the study, biochemical laboratory parameters, duration of disease, liver biopsy scores, and medication were evaluated. Additionally body mass index and body mass index centiles were calculated. Of the 96 patients in this study, 68 were male and 28 were female, and the mean age was 144.7±43.9 months and 146.1±47.3 months, respectively. According to body mass index centiles five (5.2%) patients were underweight, seven (7.3%) patients were overweight, and seven (7.3%) patients were obese. Moderate rates of malnutrition (including obesity) were found in chronic hepatitis B infection. Additional nutritional status information of healthy and sick children should be assessed in the infection's early period, and timely interventions should be initiated.

  3. Data on IL-10R neutralization-induced chronic colitis in Lipocalin 2 deficient mice on BALB/c background

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    Vishal Singh

    2017-04-01

    Full Text Available The data herein is related to the research article entitled “Microbiota-inducible Innate Immune, Siderophore Binding Protein Lipocalin 2 is Critical for Intestinal Homeostasis” (Singh et al., 2016 [1] where we have demonstrated that C57BL/6 Lipocalin 2 deficient mice (Lcn2KO developed chronic colitis upon anti-interleukin-10 receptor (αIL-10R monoclonal antibody administration. In the present article, we evaluated the susceptibility of BALB/c Lcn2KO mice and their WT littermates to the αIL-10R neutralization-induced chronic colitis. Our data showed that αIL-10R mAb-treated BALB/c Lcn2KO mice exhibited severe chronic colitis (i.e., splenomegaly, colomegaly, colonic pathology, and incidence of rectal prolapse when compared to WT mice.

  4. No Evidence that Infection Alters Global Recombination Rate in House Mice.

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    Beth L Dumont

    Full Text Available Recombination rate is a complex trait, with genetic and environmental factors shaping observed patterns of variation. Although recent studies have begun to unravel the genetic basis of recombination rate differences between organisms, less attention has focused on the environmental determinants of crossover rates. Here, we test the effect of one ubiquitous environmental pressure-bacterial infection-on global recombination frequency in mammals. We applied MLH1 mapping to assay global crossover rates in male mice infected with the pathogenic bacterium Borrelia burgdorferi, the causative agent of Lyme Disease, and uninfected control animals. Despite ample statistical power to identify biologically relevant differences between infected and uninfected animals, we find no evidence for a global recombination rate response to bacterial infection. Moreover, broad-scale patterns of crossover distribution, including the number of achiasmate bivalents, are not affected by infection status. Although pathogen exposure can plastically increase recombination in some species, our findings suggest that recombination rates in house mice may be resilient to at least some forms of infection stress. This negative result motivates future experiments with alternative house mouse pathogens to evaluate the generality of this conclusion.

  5. Chronic corticosterone exposure reduces hippocampal glycogen level and induces depression-like behavior in mice.

    Science.gov (United States)

    Zhang, Hui-yu; Zhao, Yu-nan; Wang, Zhong-li; Huang, Yu-fang

    2015-01-01

    Long-term exposure to stress or high glucocorticoid levels leads to depression-like behavior in rodents; however, the cause remains unknown. Increasing evidence shows that astrocytes, the most abundant cells in the central nervous system (CNS), are important to the nervous system. Astrocytes nourish and protect the neurons, and serve as glycogen repositories for the brain. The metabolic process of glycogen, which is closely linked to neuronal activity, can supply sufficient energy substrates for neurons. The research team probed into the effects of chronic corticosterone (CORT) exposure on the glycogen level of astrocytes in the hippocampal tissues of male C57BL/6N mice in this study. The results showed that chronic CORT injection reduced hippocampal neurofilament light protein (NF-L) and synaptophysin (SYP) levels, induced depression-like behavior in male mice, reduced hippocampal glycogen level and glycogen synthase activity, and increased glycogen phosphorylase activity. The results suggested that the reduction of the hippocampal glycogen level may be the mechanism by which chronic CORT treatment damages hippocampal neurons and induces depression-like behavior in male mice.

  6. Withdrawal from Chronic Nicotine Administration Impairs Contextual Fear Conditioning in C57BL/6 Mice

    OpenAIRE

    Davis, Jennifer A.; James, John R.; Siegel, Steven J.; Gould, Thomas J.

    2005-01-01

    The effects of acute nicotine administration (0.09 mg/kg nicotine), chronic nicotine administration (6.3 mg/kg/d nicotine for 14 d), and withdrawal from chronic nicotine administration on fear conditioning in C57BL/6 mice were examined. Mice were trained using two coterminating conditioned stimulus (30 s; 85 dB white noise)– unconditioned stimulus (2 s; 0.57 mA foot shock) pairings and tested 24 h later for contextual and cued fear conditioning. Acute nicotine administration enhanced contextu...

  7. Hepatitis B surface antigen (HBsAg) and core antigen (HBcAg) combine CpG oligodeoxynucletides as a novel therapeutic vaccine for chronic hepatitis B infection.

    Science.gov (United States)

    Li, Jianqiang; Ge, Jun; Ren, Sulin; Zhou, Tong; Sun, Ying; Sun, Honglin; Gu, Yue; Huang, Hongying; Xu, Zhenxing; Chen, Xiaoxiao; Xu, Xiaowei; Zhuang, Xiaoqian; Song, Cuiling; Jia, Fangmiao; Xu, Aiguo; Yin, Xiaojin; Du, Sean X

    2015-08-20

    Hepatitis B virus infection is a non-cytopathic hepatotropic virus which can lead to chronic liver disease and hepatocellular carcinoma. Traditional therapies fail to provide sustained control of viral replication and liver damage in most patients. As an alternative strategy, immunotherapeutic approaches have shown promising efficacy in the treatment of chronic hepatitis B patients. Here, we investigated the efficacy of a novel therapeutic vaccine formulation consisting of two HBV antigens, HBsAg and HBcAg, and CpG adjuvant. This vaccine formulation elicits forceful humoral responses directed against HBsAg/HBcAg, and promotes a Th1/Th2 balance response against HBsAg and a Th1-biased response against HBcAg in both C57BL/6 and HBV transgenic mice. Vigorous cellular immune response was also detected in HBV transgenic mice, for a significantly higher number of HBs/HBc-specific IFN-γ secreting CD4+ and CD8+ T cells was generated. Moreover, vaccinated mice elicited significantly intense in vivo CTL attack, reduced serum HBsAg level without causing liver damage in HBV transgenic mice. In summary, this study demonstrates a novel therapeutic vaccine with the potential to elicit vigorous humoral and cellular response, overcoming tolerance in HBV transgenic mice. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Pharmacologic inhibition of COX-1 and COX-2 in influenza A viral infection in mice.

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    Michelle A Carey

    Full Text Available BACKGROUND: We previously demonstrated that cyclooxygenase (COX-1 deficiency results in greater morbidity and inflammation, whereas COX-2 deficiency leads to reduced morbidity, inflammation and mortality in influenza infected mice. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the effects of COX-1 and COX-2 inhibitors in influenza A viral infection. Mice were given a COX-1 inhibitor (SC-560, a COX-2 inhibitor (celecoxib or no inhibitor beginning 2 weeks prior to influenza A viral infection (200 PFU and throughout the course of the experiment. Body weight and temperature were measured daily as indicators of morbidity. Animals were sacrificed on days 1 and 4 post-infection and bronchoalveolar lavage (BAL fluid was collected or daily mortality was recorded up to 2 weeks post-infection. Treatment with SC-560 significantly increased mortality and was associated with profound hypothermia and greater weight loss compared to celecoxib or control groups. On day 4 of infection, BAL fluid cells were modestly elevated in celecoxib treated mice compared to SC-560 or control groups. Viral titres were similar between treatment groups. Levels of TNF-alpha and G-CSF were significantly attenuated in the SC-560 and celecoxib groups versus control and IL-6 levels were significantly lower in BAL fluid of celecoxib treated mice versus control and versus the SC-560 group. The chemokine KC was significantly lower in SC-560 group versus control. CONCLUSIONS/SIGNIFICANCE: Treatment with a COX-1 inhibitor during influenza A viral infection is detrimental to the host whereas inhibition of COX-2 does not significantly modulate disease severity. COX-1 plays a critical role in controlling the thermoregulatory response to influenza A viral infection in mice.

  9. Effect of wide spectrum anti-helminthic drugs upon Schistosoma mansoni experimentally infected mice

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    PANCERA Christiane Finardi

    1997-01-01

    Full Text Available Mebendazole, albendazole, levamisole and thiabendazole are well known as active drugs against several nematode species, and against cestodes as well, when the first two drugs are considered. None of the drugs have proven activity, however, against trematodes. We tested the effect of these drugs on the fecal shedding of schistosome eggs and the recovering of adult schistosomes, after portal perfusion in Schistosoma mansoni experimentally infected mice. Balb/c mice infected with 80 S. mansoni cercariae were divided into three groups, each in turn subdivided into four other groups, for each tested drug. The first group was treated with each one of the studied drugs 25 days after S. mansoni infection; the second group was submitted to treatment with each one of the drugs 60 days after infection. Finally, the third group, considered as control, received no treatment. No effect upon fecal shedding of S. mansoni eggs and recovering of schistosomes after portal perfusion was observed when mice were treated with either mebendazole or albendazole. Mice treated with either levamisole or thiabendazole, on the other hand, showed a significant reduction in the recovering of adult schistosomes after portal perfusion, mainly when both drugs were given during the schistosomula evolution period, i.e., 25 days after cercariae penetration, probably due to unspecific immunomodulation

  10. Fluvoxamine moderates reduced voluntary activity following chronic dexamethasone infusion in mice via recovery of BDNF signal cascades.

    Science.gov (United States)

    Terada, Kazuki; Izumo, Nobuo; Suzuki, Biora; Karube, Yoshiharu; Morikawa, Tomomi; Ishibashi, Yukiko; Kameyama, Toshiki; Chiba, Koji; Sasaki, Noriko; Iwata, Keiko; Matsuzaki, Hideo; Manabe, Takayuki

    2014-04-01

    Major depression is a complex disorder characterized by genetic and environmental interactions. Selective serotonin reuptake inhibitors (SSRIs) effectively treat depression. Neurogenesis following chronic antidepressant treatment activates brain derived neurotrophic factor (BDNF) signaling. In this study, we analyzed the effects of the SSRI fluvoxamine (Flu) on locomotor activity and forced-swim behavior using chronic dexamethasone (cDEX) infusions in mice, which engenders depression-like behavior. Infusion of cDEX decreased body weight and produced a trend towards lower locomotor activity during darkness. In the forced-swim test, cDEX-mice exhibited increased immobility times compared with mice administered saline. Flu treatment reversed decreased locomotor activity and mitigated forced-swim test immobility. Real-time polymerase chain reactions using brain RNA samples yielded significantly lower BDNF mRNA levels in cDEX-mice compared with the saline group. Endoplasmic reticulum stress-associated X-box binding protein-1 (XBP1) gene expression was lower in cDEX-mice compared with the saline group. However, marked expression of the XBP1 gene was observed in cDEX-mice treated with Flu compared with mice given saline and untreated cDEX-mice. Expression of 5-HT2A and Sigma-1 receptors decreased after cDEX infusion compared with the saline group, and these decreases normalized to control levels upon Flu treatment. Our results indicate that the Flu moderates reductions in voluntary activity following chronic dexamethasone infusions in mice via recovery of BDNF signal cascades. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Bone marrow-derived microglia infiltrate into the paraventricular nucleus of chronic psychological stress-loaded mice.

    Directory of Open Access Journals (Sweden)

    Koji Ataka

    Full Text Available BACKGROUND: Microglia of the central nervous system act as sentinels and rapidly react to infection or inflammation. The pathophysiological role of bone marrow-derived microglia is of particular interest because they affect neurodegenerative disorders and neuropathic pain. The hypothesis of the current study is that chronic psychological stress (chronic PS induces the infiltration of bone marrow-derived microglia into hypothalamus by means of chemokine axes in brain and bone marrow. METHODS AND FINDINGS: Here we show that bone marrow-derived microglia specifically infiltrate the paraventricular nucleus (PVN of mice that received chronic PS. Bone marrow derived-microglia are CX3CR1(lowCCR2(+CXCR4(high, as distinct from CX3CR1(highCCR2(-CXCR4(low resident microglia, and express higher levels of interleukin-1β (IL-1β but lower levels of tumor necrosis factor-α (TNF-α. Chronic PS stimulates the expression of monocyte chemotactic protein-1 (MCP-1 in PVN neurons, reduces stromal cell-derived factor-1 (SDF-1 in the bone marrow and increases the frequency of CXCR4(+ monocytes in peripheral circulation. And then a chemokine (C-C motif receptor 2 (CCR2 or a β3-adrenoceptor blockade prevents infiltration of bone marrow-derived microglia in the PVN. CONCLUSION: Chronic PS induces the infiltration of bone marrow-derived microglia into PVN, and it is conceivable that the MCP-1/CCR2 axis in PVN and the SDF-1/CXCR4 axis in bone marrow are involved in this mechanism.

  12. Cytokine responses of CD4+ T cells during a Plasmodium chabaudi chabaudi (ER blood-stage infection in mice initiated by the natural route of infection

    Directory of Open Access Journals (Sweden)

    Butcher Geoffrey

    2007-06-01

    Full Text Available Abstract Background Investigation of host responses to blood stages of Plasmodium spp, and the immunopathology associated with this phase of the life cycle are often performed on mice infected directly with infected red blood cells. Thus, the effects of mosquito bites and the pre-erythrocytic stages of the parasite, which would be present in natural infection, are ignored In this paper, Plasmodium chabaudi chabaudi infections of mice injected directly with infected red blood cells were compared with those of mice infected by the bites of infected mosquitoes, in order to determine whether the courses of primary infection and splenic CD4 T cell responses are similar. Methods C57Bl/6 mice were injected with red blood cells infected with P. chabaudi (ER or infected via the bite of Anopheles stephensi mosquitoes. Parasitaemia were monitored by Giemsa-stained thin blood films. Total spleen cells, CD4+ T cells, and cytokine production (IFN-γ, IL-2, IL-4, IL-10 were analysed by flow cytometry. In some experiments, mice were subjected to bites of uninfected mosquitoes prior to infectious bites in order to determine whether mosquito bites per se could affect a subsequent P. chabaudi infection. Results P. chabaudi (ER infections initiated by mosquito bite were characterized by lower parasitaemia of shorter duration than those observed after direct blood challenge. However, splenomegaly was comparable suggesting that parasitaemia alone does not account for the increase in spleen size. Total numbers of CD4 T cells and those producing IFN-γ, IL-10 and IL-2 were reduced in comparison to direct blood challenge. By contrast, the reduction in IL-4 producing cells was less marked suggesting that there is a proportionally lower Th1-like response in mice infected via infectious mosquitoes. Strikingly, pre-exposure to bites of uninfected mosquitoes reduced the magnitude and duration of the subsequent mosquito-transmitted infection still further, but enhanced the

  13. Chronic hepatitis E virus infection in liver transplant recipients

    NARCIS (Netherlands)

    Haagsma, Elizabeth B.; van den Berg, Arie P.; Porte, Robert J.; Benne, Cornelis A.; Vennema, Harry; Reimerink, Johan H. J.; Koopmans, Marion P. G.

    Hepatitis E virus (HEV) infection is known to run a self-limiting course. Sporadic cases of acute hepatitis due to infection with HEV genotype 3, present in pig populations, are increasingly recognized. Zoonotic transmission seems infrequent. The entity of unexplained chronic hepatitis after liver

  14. Role of major histocompatibility complex class II in resistance of mice to naturally acquired infection with Syphacia obvelata

    Science.gov (United States)

    Stewart, Patricia W.; Chapes, Stephen K.

    2003-01-01

    Genetics plays a substantial role in host resistance in many host-parasite interactions. We examined the prevalence of naturally acquired infection with Syphacia obvelata in a number of mouse strains housed in a non-barrier facility. These mice, which included cross-bred and congenic, inbred strains on various genetic backgrounds, differ in the loci for the immune function genes--major histocompatibility complex class II (MHCII), toll-like receptor 4 (Tlr4), and solute carrier family 11, member 1 (Slc11a1)--which allowed comparisons of the impact of these genes on resistance to pinworm infection. Male and female mice of various ages were sampled over an 18-month period; infection was determined by use of the cellophane tape test. Results indicated that mice that were MHCII+/+ had a significantly lower prevalence of infection than did mice that were MHCII-/-. Differences were not seen between male and female mice. Although MHCII+/+ mice had an age-associated decrease in infection prevalence, such decrease was not seen in MHCII-/- mice. In contrast, infection prevalence in mice with the normal Tlr4 gene (Tlr4(LPS-n/LPS-n)) gene did not differ significantly compared with that in mice that were homozygous for either the point mutation (Tlr4(LPS-d/LPS-d)) or deletion (Tlr4(LPS-del/LPS-del)) of that gene. Likewise, the presence (Sle11a1r/r) or absence (Slc11a1s/s) of functional alleles for Slc11a1 had no effect on the prevalence of infection with S. obvelata. In conclusion, presence of MHCII, but not Tlr4 or Slc11a1 significantly influences prevalence of naturally acquired infection with S. obvelata. These data justify further comprehensive analyses of the immune components that are involved in pinworm resistance.

  15. Development of infection with Streptococcus bovis and Aspergillus sp. in irradiated mice after glycopeptide therapy

    International Nuclear Information System (INIS)

    Brook, I.; Tom, S.P.; Ledney, G.D.

    1993-01-01

    The use of ofloxacin and glycopeptides was evaluated for the treatment of infections arising in C3H/HeN female mice irradiated with 8.3 Gy from a 60 Co source. The 21 day regimen began 72 h after irradiation when each of five sets of experimental animals received three antimicrobial therapy regimens and a saline-treated control group. With 40 mice in each group, 20 were used to monitor survival, 20 for the recovery of bacteria from the liver culture. Treatment groups were oral ofloxacin; oral or intramuscular vancomycin oral teicoplanin, ofloxacin and vancomycin; ofloxacin and teicoplanin; or saline. Bacteria recovered from saline treated mice were Enterobacteriaceae and Streptococcus spp. By comparison, fewer Enterobacteriaceae were isolated from ofloxacin treated mice and fewer Streptococcus spp. in both vancomycin and teicoplanin treated mice. However, glycopeptide-treated mice developed infection with Aspergillis fumigatus and glycopeptide resistant Streptococcus bovis. Mortality rates within 60 days of irradiation were 100% in all treatment and control groups with the exception of ofloxacin which was 25%-35%. These data suggest that glycopeptide therapy increases rates of systemic infection with fungi and antibiotic resistant bacteria in irradiated mice. (Author)

  16. Development of infection with Streptococcus bovis and Aspergillus sp. in irradiated mice after glycopeptide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Brook, I.; Tom, S.P.; Ledney, G.D. (Armed Forces Radiobiology Research Inst., Bethesda, MD (United States))

    1993-11-01

    The use of ofloxacin and glycopeptides was evaluated for the treatment of infections arising in C3H/HeN female mice irradiated with 8.3 Gy from a [sup 60]Co source. The 21 day regimen began 72 h after irradiation when each of five sets of experimental animals received three antimicrobial therapy regimens and a saline-treated control group. With 40 mice in each group, 20 were used to monitor survival, 20 for the recovery of bacteria from the liver culture. Treatment groups were oral ofloxacin; oral or intramuscular vancomycin oral teicoplanin, ofloxacin and vancomycin; ofloxacin and teicoplanin; or saline. Bacteria recovered from saline treated mice were Enterobacteriaceae and Streptococcus spp. By comparison, fewer Enterobacteriaceae were isolated from ofloxacin treated mice and fewer Streptococcus spp. in both vancomycin and teicoplanin treated mice. However, glycopeptide-treated mice developed infection with Aspergillis fumigatus and glycopeptide resistant Streptococcus bovis. Mortality rates within 60 days of irradiation were 100% in all treatment and control groups with the exception of ofloxacin which was 25%-35%. These data suggest that glycopeptide therapy increases rates of systemic infection with fungi and antibiotic resistant bacteria in irradiated mice. (Author).

  17. Salmonella Typhimurium gastroenteritis leading to chronic prosthetic vascular graft infection.

    Science.gov (United States)

    Cullinan, Milo; Clarke, Michael; Dallman, Tim; Peart, Steven; Wilson, Deborah; Weiand, Daniel

    2017-08-01

    Introduction. It is estimated up to 6 % of prosthetic vascular grafts become infected. Staphylococcus aureus is predominant in early infection and coagulase-negative staphylococci are predominant in late infections. Enterobacteriaceae cause 14-40 % of prosthetic vascular graft infections. This is, to our knowledge the first reported case of Salmonella gastroenteritis causing chronic prosthetic vascular graft infection (PVGI). Case presentation. A 57 years old lady presented with signs and symptoms of prosthetic vascular graft infection. Three years earlier, she had undergone a prosthetic axillo-femoral bypass graft for critical limb ischaemia. The infected prosthetic vascular graft was removed and Salmonella Typhimurium was isolated on culture. In the intervening period, Salmonella Typhimurium was isolated from a faecal specimen, collected during an episode of acute gastroenteritis. Whole-genome sequencing (WGS) showed that the respective Salmonella Typhimurium isolates differed by only a single nucleotide polymorphism (SNP). Salmonella Typhimurium was not isolated on culture of a faecal specimen collected five days following cessation of antimicrobial therapy. Six months after removal of the prosthetic graft, the patient remains under follow-up for her peripheral vascular disease, which currently requires no further surgical intervention. Conclusion. This case has clear implications for the management of chronic PVGI. It is vital to collect high-quality surgical specimens for microbiological analysis and empirical choices of antibiotics are unlikely to cover all potential pathogens. It may also be prudent to enquire about a history of acute gastroenteritis when assessing patients presenting with chronic PVGI.

  18. Does bovine besnoitiosis affect the sexual function of chronically infected bulls?

    Science.gov (United States)

    Esteban-Gil, A; Jacquiet, P; Florentin, S; Decaudin, A; Berthelot, X; Ronsin, P; Grisez, C; Prevot, F; Alzieu, J P; Marois, M; Corboz, N; Peglion, M; Vilardell, C; Liénard, E; Bouhsira, E; Castillo, J A; Franc, M; Picard-Hagen, N

    2016-09-15

    Bovine besnoitiosis is a reemerging disease in Europe. The clinically Besnoitia besnoiti infection in bulls is characterized by fever, nasal discharge, and orchitis in the acute phase and by scleroderma in the chronic phase. However, in many bulls, B besnoiti infection remains at a subclinical stage. Bull infertility is an economically relevant consequence of besnoitiosis infection. It is not clear, however, if semen quality returns to normal levels when infected animals have clinically recovered. The aim of this study was to examine the relationship between chronic besnoitiosis and bull sexual function in a region of eastern France, where the disease is reemerging, by comparing semen quality and genital lesions in 11 uninfected, 17 subclinically infected, and 12 clinically infected bulls. The presence of anti-B besnoiti antibodies was detected by Western blot test. Semen was collected by electroejaculation. Bulls clinically infected with B besnoiti showed significantly more genital tract alterations than uninfected or subclinically infected bulls. No relationship was evidenced between besnoitiosis infectious status and semen quality, whereas a significant relationship was noted between genital lesions and semen score. This means that in the absence of moderate to severe genital lesions, chronic bovine besnoitiosis is unlikely to alter semen quality. However, as the presence of infected animals could lead to spread of the disease, culling or separation of clinically infected bulls from the remaining healthy animals is strongly recommended. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Chronic liver injury in mice promotes impairment of skin barrier function via tumor necrosis factor-alpha.

    Science.gov (United States)

    Yokoyama, Satoshi; Hiramoto, Keiichi; Koyama, Mayu; Ooi, Kazuya

    2016-09-01

    Alcohol is frequently used to induce chronic liver injury in laboratory animals. Alcohol causes oxidative stress in the liver and increases the expression of inflammatory mediators that cause hepatocellular damage. However, during chronic liver injury, it is unclear if/how these liver-derived factors affect distal tissues, such as the skin. The purpose of this study was to evaluate skin barrier function during chronic liver injury. Hairless mice were administered 5% or 10% ethanol for 8 weeks, and damages to the liver and skin were assessed using histological and protein-analysis methods, as well as by detecting inflammatory mediators in the plasma. After alcohol administration, the plasma concentration of the aspartate and alanine aminotransferases increased, while albumin levels decreased. In mice with alcohol-induced liver injury, transepidermal water loss was significantly increased, and skin hydration decreased concurrent with ceramide and type I collagen degradation. The plasma concentrations of [Formula: see text]/[Formula: see text] and tumor necrosis factor-alpha (TNF-α) were significantly increased in mice with induced liver injury. TNF receptor (TNFR) 2 expression was upregulated in the skin of alcohol-administered mice, while TNFR1 levels remained constant. Interestingly, the impairment of skin barrier function in mice administered with 10% ethanol was ameliorated by administering an anti-TNF-α antibody. We propose a novel mechanism whereby plasma TNF-α, via TNFR2 alone or with TNFR1, plays an important role in skin barrier function during chronic liver disease in these mouse models.

  20. Impact of chronic low to moderate alcohol consumption on blood lipid and heart energy profile in acetaldehyde dehydrogenase 2-deficient mice.

    Science.gov (United States)

    Fan, Fan; Cao, Quan; Wang, Cong; Ma, Xin; Shen, Cheng; Liu, Xiang-wei; Bu, Li-ping; Zou, Yun-zeng; Hu, Kai; Sun, Ai-jun; Ge, Jun-bo

    2014-08-01

    To investigate the roles of acetaldehyde dehydrogenase 2 (ALDH2), the key enzyme of ethanol metabolism, in chronic low to moderate alcohol consumption-induced heart protective effects in mice. Twenty-one male wild-type (WT) or ALDH2-knockout (KO) mice were used in this study. In each genotype, 14 animals received alcohol (2.5%, 5% and 10% in week 1-3, respectively, and 18% in week 4-7), and 7 received water for 7 weeks. After the treatments, survival rate and general characteristics of the animals were evaluated. Serum ethanol and acetaldehyde levels and blood lipids were measured. Metabolomics was used to characterize the heart and serum metabolism profiles. Chronic alcohol intake decreased the survival rate of KO mice by 50%, and significantly decreased their body weight, but did not affect those of WT mice. Chronic alcohol intake significantly increased the serum ethanol levels in both WT and KO mice, but KO mice had significantly higher serum acetaldehyde levels than WT mice. Chronic alcohol intake significantly increased the serum HDL cholesterol levels in WT mice, and did not change the serum HDL cholesterol levels in KO mice. After chronic alcohol intake, WT and KO mice showed differential heart and serum metabolism profiles, including the 3 main energy substrate types (lipids, glucose and amino acids) and three carboxylic acid cycles. Low to moderate alcohol consumption increases HDL cholesterol levels and improves heart energy metabolism profile in WT mice but not in ALDH2-KO mice. Thus, preserved ALDH2 function is essential for the protective effect of low to moderate alcohol on the cardiovascular system.

  1. Lentinan treatment of Plasmodium yoelii-infected mice induces ...

    African Journals Online (AJOL)

    Yomi

    2012-01-31

    Jan 31, 2012 ... infected mice results in down-regulation of the Th1-type immune response, leading to death (Wu et al., 2007;. Amante et al., 2007). Thus, these cells help to promote the pathogenesis of malaria. Several treatments are commonly used to combat malaria; most often is quinine administration (Sahu et al.,.

  2. Dexamethasone treatment induces susceptibility of outbred Webster mice to experimental infection with Besnoitia darlingi isolated from opossums (Didelphis virginiana).

    Science.gov (United States)

    Elsheikha, Hany M; Rosenthal, Benjamin M; Mansfield, Linda S

    2005-04-01

    The Sarcocystidae comprise a diverse, monophyletic apicomplexan parasite family, most of whose members form intracellular cysts in their intermediate hosts. The extent of pathology associated with such cyst formation can range widely. We currently lack experimental animal models for many of these infections. Here we explored dexamethasone treatment as a means to render outbred mice susceptible to Besnoitia darlingi infection and demonstrated that this approach allows viable parasites to be subsequently isolated from these mice and maintained in tissue culture. Besnoitia bradyzoites recovered from crushed cysts derived from naturally infected opossums (Didelphis virginiana) replicated and reproduced the development of besnoitiosis in mice treated with dexamethasone (0.5 mg/ml drinking water) daily for 12 days post infection (DPI). Isolates recovered from the peritoneal exudates of these mice were viable and were maintained in long-term tissue cultures. In contrast, control mice given saline without dexamethasone and challenged with similar bradyzoites remained clinically normal for up to 70 DPI. An additional group of mice challenged with the same inoculum of bradyzoites and given dexamethasone at the same concentration and treated with sulfadiazine (1 mg/ml drinking water) daily for 12 DPI also remained normal for up to 70 DPI. Severe disease developed more rapidly in dexamethasone-treated mice inoculated with culture-derived B. darlingi tachyzoites than in those inoculated with cyst-derived bradyzoites. B. darlingi tachyzoite-infected, untreated control mice developed signs of illness at 18 DPI. In contrast, mice treated with sulfadiazine showed no clinical signs up to 50 DPI. Although dexamethasone treatment was required to establish B. darlingi infection in outbred mice inoculated with opossum-derived B. darlingi bradyzoites, no such treatment was required for mice inoculated with culture-derived B. darlingi tachyzoites. Finally, sulfadiazine was highly

  3. Influence of environmental enrichment on the behavior and physiology of mice infected by Trypanosoma cruzi

    Directory of Open Access Journals (Sweden)

    Déborah Maria Moreira da Silva

    Full Text Available Abstract INTRODUCTION: Enriched environments normally increase behavioral repertoires and diminish the expression of abnormal behaviors and stress-related physiological problems in animals. Although it has been shown that experimental animals infected with microorganisms can modify their behaviors and physiology, few studies have evaluated how environmental enrichment affects these parameters. This study aimed to evaluate the effects of environmental enrichment on the behavior and physiology of confined mice infected with Trypanosoma cruzi. METHODS: The behaviors of 20 T. cruzi-infected mice and 20 non-infected mice were recorded during three treatments: baseline, enrichment, and post-enrichment. Behavioral data were collected using scan sampling with instantaneous recording of behavior every 30s, totaling 360h. Plasma TNF, CCL2, and IL-10 levels and parasitemia were also evaluated in infected enriched/non-enriched mice. Behavioral data were evaluated by Friedman’s test and physiological data by one-way ANOVA and area under the curve (AUC analysis. RESULTS: Results showed that environmental enrichment significantly increased exploratory behaviors and diminished inactivity. The use of environmental enrichment did not diminish circulating levels of TNF and IL-10 but diminished circulating levels of CCL2 and parasitemia. CONCLUSIONS: Positive behavioral and physiological effects of environmental enrichment were observed in mice living in enriched cages. Thus, environmental enrichment improved the welfare of these animals.

  4. Proteomic Analysis of Leptospira interrogans Shed in Urine of Chronically Infected Hosts▿

    OpenAIRE

    Monahan, Avril M.; Callanan, John J.; Nally, Jarlath E.

    2008-01-01

    Leptospirosis is a global zoonotic disease. The causative agent, pathogenic Leptospira species, survives in the renal tubules of chronically infected hosts, from where leptospires are shed via urine into the environment. Infection of new hosts can present as an array of acute and chronic disease processes reflecting variations in host-pathogen interactions. The present study was designed to reproduce the carrier phase of infection in Rattus norvegicus, thus facilitating shedding of leptospire...

  5. Lactoferricin but not lactoferrin inhibit herpes simplex virus type 2 infection in mice.

    Science.gov (United States)

    Shestakov, Andrey; Jenssen, Håvard; Nordström, Inger; Eriksson, Kristina

    2012-03-01

    We have evaluated the potential of bovine lactoferrin and lactoferricin for their ability to prevent and/or treat genital HSV-2 infection in mice. We confirm previous data showing that both lactoferrin and lactoferricin have antiviral properties in vitro and can inhibit HSV-2 infection of GMK cells in a dose-dependent manner. When tested in vivo, lactoferricin but not lactoferrin was also a potent inhibitor of HSV-2 infection. When admixed with virus prior to inoculation, lactoferricin inhibited disease development and significantly reduced the viral load in a genital model of HSV-2 infection in mice. Lactoferrin and lactoferricin were also tested for their ability to stimulate the production of chemokines. Neither of the compounds induced the production of CCL3, CCL5, CXCL1 or CXCL2 by mouse splenocytes in vitro. However, when tested in vivo, both lactoferrin and lactoferricin were able to induce local vaginal production of CCL5. Lactoferrin also induced CXCL2 production. The prophylactic and/or therapeutic effects of lactoferrin or lactoferricin were also tested. But none of the compounds were efficient in blocking HSV-2 infection when given 24h prior to HSV-2 infection. Lactoferricin however showed promising results as a therapeutic agent and delayed both disease onset by 3days as well as reducing the viral load almost 15-fold when given as a single dose 24h post-infection. These data show that lactoferricin can block genital herpes infection in mice, and perhaps also be used for post-infection treatment. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. The role of neutrophils in the upper and lower respiratory tract during influenza virus infection of mice

    Directory of Open Access Journals (Sweden)

    Reading Patrick C

    2008-08-01

    Full Text Available Abstract Background Neutrophils have been shown to play a role in host defence against highly virulent and mouse-adapted strains of influenza virus, however it is not clear if an effective neutrophil response is an important factor moderating disease severity during infection with other virus strains. In this study, we have examined the role of neutrophils during infection of mice with influenza virus strain HKx31, a virus strain of the H3N2 subtype and of moderate virulence for mice, to determine the role of neutrophils in the early phase of infection and in clearance of influenza virus from the respiratory tract during the later phase of infection. Methods The anti-Gr-1 monoclonal antibody (mAb RB6-8C5 was used to (i identify neutrophils in the upper (nasal tissues and lower (lung respiratory tract of uninfected and influenza virus-infected mice, and (ii deplete neutrophils prior to and during influenza virus infection of mice. Results Neutrophils were rapidly recruited to the upper and lower airways following influenza virus infection. We demonstrated that use of mAb RB6-8C5 to deplete C57BL/6 (B6 mice of neutrophils is complicated by the ability of this mAb to bind directly to virus-specific CD8+ T cells. Thus, we investigated the role of neutrophils in both the early and later phases of infection using CD8+ T cell-deficient B6.TAP-/- mice. Infection of B6.TAP-/- mice with a low dose of influenza virus did not induce clinical disease in control animals, however RB6-8C5 treatment led to profound weight loss, severe clinical disease and enhanced virus replication throughout the respiratory tract. Conclusion Neutrophils play a critical role in limiting influenza virus replication during the early and later phases of infection. Furthermore, a virus strain of moderate virulence can induce severe clinical disease in the absence of an effective neutrophil response.

  7. 75 FR 55797 - Draft Guidance for Industry on Chronic Hepatitis C Virus Infection: Developing Direct-Acting...

    Science.gov (United States)

    2010-09-14

    ...] Draft Guidance for Industry on Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral... entitled ``Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Agents for Treatment... announcing the availability of a draft guidance for industry entitled ``Chronic Hepatitis C Virus Infection...

  8. Cytokine gene expression and pathology in mice experimentally infected with different isolates of Trypanosoma evansi.

    Science.gov (United States)

    Krishnamoorthy, P; Sengupta, P P; Das, Sangita; Ligi, M; Shome, B R; Rahman, H

    2016-11-01

    Aim of the present study was to assess the cytokine gene expression in liver, kidney and spleen and histopathological changes in mice infected with buffalo and dog isolates of Trypanosoma evansi. Forty-four Swiss albino mice was divided into eleven groups of four mice each and injected subcutaneously with 1 × 10 5 trypanosomes of buffalo and dog isolate to twenty mice each, four mice served as control. Mice were examined for clinical signs, blood smear for trypanosome counts. Blood for PCR, liver, kidney, spleen, heart, lung, testis and abdominal muscle for histopathology and liver, kidney, spleen for cytokine gene expression studies, were collected. Mice showed dullness, lethargy, hunched back, sluggish movements on D4 and D5 in buffalo and dog isolate, respectively. Parasite count in blood varied between the two isolates of T. evansi. By PCR, trypanosome DNA was detected on D1 and D2 for buffalo and dog isolate, respectively. Splenomegaly was observed in mice infected with buffalo isolate but not with dog isolate. Histopathological changes were observed in liver, kidney, spleen and heart of mice but no changes in testis and abdominal muscles. Blood vessels of liver, heart, lung showed presence of trypanosomes in mice infected with buffalo isolate but not for dog isolate. Cytokine gene expression of IL-2, IL-4, IL-6, IL-12, TNF-α and IFN-γ increased in liver, kidney and spleen in both these isolates. However, the buffalo isolate exhibited pronounced increase in cytokine gene expression when compare to dog isolate of T. evansi. Anti-inflammatory cytokine gene IL-10 showed 50-60 and 10-20 folds increment in buffalo and dog isolates, respectively. This is the first report of IL-4, IL-6, IL-10 and IL-12 cytokine changes in mice infected with T. evansi. A variation in pathogenicity between buffalo and dog isolates was recorded indicating buffalo isolate of T. evansi remained more pathogenic in mice. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Autoimmune and Neoplastic Thyroid Diseases Associated with Hepatitis C Chronic Infection

    Directory of Open Access Journals (Sweden)

    Poupak Fallahi

    2014-01-01

    Full Text Available Frequently, patients with hepatitis C virus (HCV chronic infection have high levels of serum anti-thyroperoxidase and/or anti-thyroglobulin autoantibodies, ultrasonographic signs of chronic autoimmune thyroiditis, and subclinical hypothyroidism, in female gender versus healthy controls, or hepatitis B virus infected patients. In patients with “HCV-associated mixed cryoglobulinemia” (MC + HCV, a higher prevalence of thyroid autoimmune disorders was shown not only compared to controls, but also versus HCV patients without cryoglobulinemia. Patients with MC + HCV or HCV chronic infection show a higher prevalence of papillary thyroid cancer than controls, in particular in patients with autoimmune thyroiditis. Patients with HCV chronic infection, or with MC + HCV, in presence of autoimmune thyroiditis, show higher serum levels of T-helper (Th1 (C-X-C motif ligand 10 (CXCL10 chemokine, but normal levels of Th2 (C-C motif ligand 2 chemokine, than patients without thyroiditis. HCV thyroid infection could act by upregulating CXCL10 gene expression and secretion in thyrocytes recruiting Th1 lymphocytes that secrete interferon-γ and tumor necrosis factor-α. These cytokines might induce a further CXCL10 secretion by thyrocytes, thus perpetuating the immune cascade, which may lead to the appearance of autoimmune thyroid disorders in genetically predisposed subjects. A careful monitoring of thyroid function, particularly where nodules occur, is recommended in HCV patients.

  10. Effect of acycloguanosine treatment of acute and latent herpes simplex infections in mice.

    Science.gov (United States)

    Field, H J; Bell, S E; Elion, G B; Nash, A A; Wildy, P

    1979-04-01

    Systemic treatment of mice with the nucleoside analog 9-(2-hydroxyethoxymethyl)guanine (acycloguanosine [aciclovir]) was found to be highly effective against acute type 1 herpes simplex virus infection of the pinna. The drug ablated clinical signs and reduced virus replication both in tissue local to the inoculation site and within the nervous system. Provided that moderate-sized virus inocula were used, acycloguanosine treatment reduced or prevented the establishment of a latent infection in the dorsal root ganglia relating to the sensory nerve supply of the ear. However, although it aborted artificially produced infections in dorsal root ganglia, acycloguanosine was found not to be effective against the latent infection once established. This finding strongly indicated that latent herpes simplex virus in mice can exist in a nonreplicating form.

  11. Radiocomplexation and evaluation of the 99mTc-Gemifloxacin in artificially Escherichia coli infected mice

    International Nuclear Information System (INIS)

    Erfani, M.; Shafiei, M.; Rekabgardan, M.; Mortazavi, P.

    2016-01-01

    Gemifloxacin as a broad spectrum quinolone antibacterial agent was radiocomplexed with high activity of 99m Tc and was evaluated as an infection imaging agent in artificially Escherichia coli (E. Coli) infected mice. 99m Tc-Gemifloxacin with high specific activity (0.148 GBq/μmol) and labeling yield (98.60 ± 0.70 %) was obtained. Our main achievement was high accumulation in the E. Coli infected right thigh muscle in mice (T/NT = 1.89 at 4 h post injection) which may diagnostically be beneficial to distinguish sites of E. Coli infection. (author)

  12. Exendin-4 improves resistance to Listeria monocytogenes infection in diabetic db/db mice

    OpenAIRE

    Liu, Hsien Yueh; Chung, Chih-Yao; Yang, Wen-Chin; Liang, Chih-Lung; Wang, Chi-Young; Chang, Chih-Yu; Chang, Cicero Lee-Tian

    2012-01-01

    The incidence of diabetes mellitus is increasing among companion animals. This disease has similar characteristics in both humans and animals. Diabetes is frequently identified as an independent risk factor for infections associated with increased mortality. In the present study, homozygous diabetic (db/db) mice were infected with Listeria (L.) monocytogenes and then treated with the anti-diabetic drug exendin-4, a glucagon-like peptide 1 analogue. In aged db/db mice, decreased CD11b+ macroph...

  13. Competitive inhibitor of cellular alpha-glucosidases protects mice from lethal dengue virus infection

    OpenAIRE

    Chang, Jinhong; Schul, Wouter; Yip, Andy; Xu, Xiaodong; Guo, Ju-Tao; Block, Timothy M.

    2011-01-01

    Dengue virus infection causes diseases in people, ranging from the acute febrile illness Dengue fever, to life-threatening Dengue Hemorrhagic Fever/Dengue Shock Syndrome. We previously reported that a host cellular α-glucosidases I and II inhibitor, imino sugar CM-10-18, potently inhibited dengue virus replication in cultured cells, and significantly reduced viremia in dengue virus infected AG129 mice. In this report we show that CM-10-18 also significantly protects mice from death and/or dis...

  14. Chronic Hepatitis B and C Virus Infection and Risk for Non-Hodgkin Lymphoma in HIV-Infected Patients

    DEFF Research Database (Denmark)

    Wang, Qing; De Luca, Andrea; Smith, Colette

    2017-01-01

    Background: Non-Hodgkin lymphoma (NHL) is the most common AIDS-defining condition in the era of antiretroviral therapy (ART). Whether chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection promote NHL in HIV-infected patients is unclear. Objective: To investigate whether chronic HBV...... and HCV infection are associated with increased incidence of NHL in HIV-infected patients. Design: Cohort study. Setting: 18 of 33 cohorts from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). Patients: HIV-infected patients with information on HBV surface antigen...... measurements and detectable HCV RNA, or a positive HCV antibody test result if HCV RNA measurements were not available. Measurements: Time-dependent Cox models to assess risk for NHL in treatment-naive patients and those initiating ART, with inverse probability weighting to control for informative censoring...

  15. Chronic caffeine exposure attenuates blast-induced memory deficit in mice.

    Science.gov (United States)

    Ning, Ya-Lei; Yang, Nan; Chen, Xing; Zhao, Zi-Ai; Zhang, Xiu-Zhu; Chen, Xing-Yun; Li, Ping; Zhao, Yan; Zhou, Yuan-Guo

    2015-01-01

    To investigate the effects of three different ways of chronic caffeine administration on blast- induced memory dysfunction and to explore the underlying mechanisms. Adult male C57BL/6 mice were used and randomly divided into five groups: control: without blast exposure, con-water: administrated with water continuously before and after blast-induced traumatic brain injury (bTBI), con-caffeine: administrated with caffeine continuously for 1 month before and after bTBI, pre-caffeine: chronically administrated with caffeine for 1 month before bTBI and withdrawal after bTBI, post-caffeine: chronically administrated with caffeine after bTBI. After being subjected to moderate intensity of blast injury, mice were recorded for learning and memory performance using Morris water maze (MWM) paradigms at 1, 4, and 8 weeks post-blast injury. Neurological deficit scoring, glutamate concentration, proinflammatory cytokines production, and neuropathological changes at 24 h, 1, 4, and 8 weeks post-bTBI were examined to evaluate the brain injury in early and prolonged stages. Adenosine A1 receptor expression was detected using qPCR. All of the three ways of chronic caffeine exposure ameliorated blast-induced memory deficit, which is correlated with the neuroprotective effects against excitotoxicity, inflammation, astrogliosis and neuronal loss at different stages of injury. Continuous caffeine treatment played positive roles in both early and prolonged stages of bTBI; pre-bTBI and post-bTBI treatment of caffeine tended to exert neuroprotective effects at early and prolonged stages of bTBI respectively. Up-regulation of adenosine A1 receptor expression might contribute to the favorable effects of chronic caffeine consumption. Since caffeinated beverages are widely consumed in both civilian and military personnel and are convenient to get, the results may provide a promising prophylactic strategy for blast-induced neurotrauma and the consequent cognitive impairment.

  16. Chronic Toxoplasma gondii in Nurr1-Null Heterozygous Mice Exacerbates Elevated Open Field Activity

    OpenAIRE

    Eells, Jeffrey B.; Varela-Stokes, Andrea; Guo-Ross, Shirley X.; Kummari, Evangel; Smith, Holly M.; Cox, Erin; Lindsay, David S.

    2015-01-01

    Latent infection with Toxoplasma gondii is common in humans (approximately 30% of the global population) and is a significant risk factor for schizophrenia. Since prevalence of T. gondii infection is far greater than prevalence of schizophrenia (0.5-1%), genetic risk factors are likely also necessary to contribute to schizophrenia. To test this concept in an animal model, Nurr1-null heterozygous (+/-) mice and wild-type (+/+) mice were evaluate using an emergence test, activity in an open fie...

  17. Chronic obstructive pulmonary disease and risk of infection

    DEFF Research Database (Denmark)

    Lange, Peter

    2009-01-01

    This review article focuses on the risk of infections in patients with chronic obstructive pulmonary disease (COPD). Throughout the years there have been a number of studies describing the risk of pulmonary infections in patients with COPD, whereas only few studies have focused on the risk...... of infection outside the lungs. With increasing severity of COPD the risk of respiratory tract infection also increases. The impairment of the innate immune system is most likely responsible for both the colonization of respiratory tract with bacteria and for an increased risk of infection with new strains...... of bacteria causing acute exacerbations. Also lung infections like pneumonia, lung abscess and empyema are more often seen in patients with COPD than in healthy subjects. With regard to extrapulmonary infections, it seems that COPD patients are not at higher risk of infection compared with subjects without...

  18. Relation of type-C RNA virus infectivity and leukemogenesis in rats and mice

    International Nuclear Information System (INIS)

    Nagao, Kenji; Ito, Takaaki; Yokoro, Kenjiro

    1976-01-01

    Observation was made as to movement of type-C RNA virus infectivity in the process of leukemogensis induced by Gross virus, N-nitrosoethylurea (NEU), or, x-ray. Total dose of 680 R in 4 times was given to the whole body or parts of the body at intervals of 5 days. Thymic leukemia occurred in 100% or rats which were inoculated with type-C RNA virus at the period of newborn 64 days after, on the average. Infectious titer of virus rose only in thymus toward leukemogenesis. Thymic leukemia was induced 100% in mice by NEU 122 days after, but its incidence was 9% of mice of which thymus was extracted. Leukemia virus was not detected in non-extracted thymus of mice, and pattern of virus infectivity in other organs did not show any difference with that of mice of which thymus was extracted. Virus showed high infectious titer in uterus of mice of both groups. Leukemia occurred 87% in the whole body irradiated mice, 15% in partially irradiated mice, and 39% in mice of which thymus was extracted and the whole body was irradiated. Virus did not show any homeostatic infectious titer in three kinds of leukemia, but it showed high infectious titer in uterus. (Kanao, N.)

  19. Glucocorticoid treatment of MCMV infected newborn mice attenuates CNS inflammation and limits deficits in cerebellar development.

    Directory of Open Access Journals (Sweden)

    Kate Kosmac

    2013-03-01

    Full Text Available Infection of the developing fetus with human cytomegalovirus (HCMV is a major cause of central nervous system disease in infants and children; however, mechanism(s of disease associated with this intrauterine infection remain poorly understood. Utilizing a mouse model of HCMV infection of the developing CNS, we have shown that peripheral inoculation of newborn mice with murine CMV (MCMV results in CNS infection and developmental abnormalities that recapitulate key features of the human infection. In this model, animals exhibit decreased granule neuron precursor cell (GNPC proliferation and altered morphogenesis of the cerebellar cortex. Deficits in cerebellar cortical development are symmetric and global even though infection of the CNS results in a non-necrotizing encephalitis characterized by widely scattered foci of virus-infected cells with mononuclear cell infiltrates. These findings suggested that inflammation induced by MCMV infection could underlie deficits in CNS development. We investigated the contribution of host inflammatory responses to abnormal cerebellar development by modulating inflammatory responses in infected mice with glucocorticoids. Treatment of infected animals with glucocorticoids decreased activation of CNS mononuclear cells and expression of inflammatory cytokines (TNF-α, IFN-β and IFNγ in the CNS while minimally impacting CNS virus replication. Glucocorticoid treatment also limited morphogenic abnormalities and normalized the expression of developmentally regulated genes within the cerebellum. Importantly, GNPC proliferation deficits were normalized in MCMV infected mice following glucocorticoid treatment. Our findings argue that host inflammatory responses to MCMV infection contribute to deficits in CNS development in MCMV infected mice and suggest that similar mechanisms of disease could be responsible for the abnormal CNS development in human infants infected in-utero with HCMV.

  20. Effect of some parasitic infection on neurotransmitters in the brain of experimentally infected mice before and after treatment.

    Science.gov (United States)

    Abdel Ghafar, A E; Elkowrany, S E; Salem, S A; Menaisy, A A; Fadel, W A; Awara, W M

    1996-08-01

    The effects of some parasitic infection (bilharziasis, toxocariasis and trichinosis) on the brain of experimentally infected mice were investigated. Eighty animals were classified into four groups, group I contained five non infected animals as a control group. The other groups each contained twenty-five mice infected with Schistosoma mansoni (group II), Toxocara canis (group III) and Trichinella spiralis (group IV). Each infected group was divided into two subgroups (a,b). Subgroup (a) left untreated and subgroups (b) treated by praziquantel (in group II) and mebendazole (in group III and IV). Histopathological and immunological examination using peroxidase antiperoxidase (PAP) technique and neurotransmitters estimation (nor-epinephrine, dopamine and serotonine) were carried. In the untreated animals, there were mild histopathological changes and mild antigenic deposition in subgroups (IIa and IIIa) and marked changes in subgroup (IVa). There were significant decrease in dopamine in subgroup (IIIa), not improved after treatment (subgroup IIIb) and significant decrease in nor-epinephrine and serotonine in subgroup (IVa) improved after treatment in subgroup (IVb). The neurotransmitters changes may explain the motor, behavioural and emotional changes that occurred with these parasites.

  1. Chronic exercise prevents repeated restraint stress-provoked enhancement of immobility in forced swimming test in ovariectomized mice.

    Science.gov (United States)

    Han, Tae-Kyung; Lee, Jang-Kyu; Leem, Yea-Hyun

    2015-06-01

    We assessed whether chronic treadmill exercise attenuated the depressive phenotype induced by restraint stress in ovariectomized mice (OVX). Immobility of OVX in the forced swimming test was comparable to that of sham mice (CON) regardless of the postoperative time. Immobility was also no difference between restrained mice (exposure to periodic restraint for 21 days; RST) and control mice (CON) on post-exposure 2nd and 9th day, but not 15th day. In contrast, the immobility of ovariectomized mice with repeated stress (OVX + RST) was profoundly enhanced compared to ovariectomized mice-alone (OVX), and this effect was reversed by chronic exercise (19 m/min, 60 min/day, 5 days/week for 8 weeks; OVX + RST + Ex) or fluoxetine administration (20 mg/kg, OVX + RST + Flu). In parallel with behavioral data, the immunoreactivity of Ki-67 and doublecortin (DCX) in OVX was significantly decreased by repeated stress. However, the reduced numbers of Ki-67- and DCX-positive cells in OVX + RST were restored in response to chronic exercise (OVX + RST + Ex) and fluoxetine (OVX + RST + Flu). In addition, the expression pattern of cAMP response element-binding protein (CREB) and calcium-calmodulin-dependent kinase IV (CaMKIV) was similar to that of the hippocampal proliferation and neurogenesis markers (Ki-67 and DCX, respectively). These results suggest that menopausal depression may be induced by an interaction between repeated stress and low hormone levels, rather than a deficit in ovarian secretion alone, which can be improved by chronic exercise.

  2. Reduction of influenza virus titer and protection against influenza virus infection in infant mice fed Lactobacillus casei Shirota.

    Science.gov (United States)

    Yasui, Hisako; Kiyoshima, Junko; Hori, Tetsuji

    2004-07-01

    We investigated whether oral administration of Lactobacillus casei strain Shirota to neonatal and infant mice ameliorates influenza virus (IFV) infection in the upper respiratory tract and protects against influenza infection. In a model of upper respiratory IFV infection, the titer of virus in the nasal washings of infant mice administered L. casei Shirota (L. casei Shirota group) was significantly (P survival rate of the L. casei Shirota group was significantly (P L. casei Shirota group were significantly greater than those of mice in the control group. These findings suggest that oral administration of L. casei Shirota activates the immature immune system of neonatal and infant mice and protects against IFV infection. Therefore, oral administration of L. casei Shirota may accelerate the innate immune response of the respiratory tract and protect against various respiratory infections in neonates, infants, and children, a high risk group for viral and bacterial infections.

  3. Chronic exposure to low concentrations of lead induces metabolic disorder and dysbiosis of the gut microbiota in mice.

    Science.gov (United States)

    Xia, Jizhou; Jin, Cuiyuan; Pan, Zihong; Sun, Liwei; Fu, Zhengwei; Jin, Yuanxiang

    2018-08-01

    Lead (Pb) is one of the most prevalent toxic, nonessential heavy metals that can contaminate food and water. In this study, effects of chronic exposure to low concentrations of Pb on metabolism and gut microbiota were evaluated in mice. It was observed that exposure of mice to 0.1mg/L Pb, supplied via drinking water, for 15weeks increased hepatic TG and TCH levels. The levels of some key genes related to lipid metabolism in the liver increased significantly in Pb-treated mice. For the gut microbiota, at the phylum level, the relative abundance of Firmicutes and Bacteroidetes changed obviously in the feces and the cecal contents of mice exposed to 0.1mg/L Pb for 15weeks. In addition, 16s rRNA gene sequencing further discovered that Pb exposure affected the structure and richness of the gut microbiota. Moreover, a 1 H NMR metabolic analysis unambiguously identified 31 metabolites, and 15 metabolites were noticeably altered in 0.1mg/L Pb-treated mice. Taken together, the data indicate that chronic Pb exposure induces dysbiosis of the gut microbiota and metabolic disorder in mice. Chronic Pb exposure induces metabolic disorder, dysbiosis of the gut microbiota and hepatic lipid metabolism disorder in mice. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. lowered serum triglyceride levels among chronic hepatitis b-infected

    African Journals Online (AJOL)

    User

    about the effect of the two pathological stages of chronic hepatitis B (CHB) infectionchronic- symptomatic and ... 2 hepatitis B disease and plasma metabolite dys- regulation has become the subject of interest by most biomedical researchers over the past dec- ade. The liver as a ..... leukin – 1, and interferon – α stimulate.

  5. Antihemolytic Activities of Green Tea, Safflower, and Mulberry Extracts during Plasmodium berghei Infection in Mice

    Directory of Open Access Journals (Sweden)

    Suthin Audomkasok

    2014-01-01

    Full Text Available Malaria-associated hemolysis is associated with mortality in adult patients. It has been speculated that oxidative stress and inflammation induced by malaria parasite are involved in its pathophysiology. Hence, we aimed to investigate the antihemolytic effect of green tea, safflower, and mulberry extracts against Plasmodium berghei infection. Aqueous crude extracts of these plants were prepared using hot water method and used for oral treatment in mice. Groups of ICR mice were infected with 6 × 106 infected red blood cells of P. berghei ANKA by intraperitoneal injection and given the extracts (500, 1500, and 3000 mg/kg twice a day for 4 consecutive days. To assess hemolysis, hematocrit levels were then evaluated. Malaria infection resulted in hemolysis. However, antihemolytic effects were observed in infected mice treated with these extracts at dose-dependent manners. In conclusion, aqueous crude extracts of green tea, safflower, and mulberry exerted antihemolysis induced by malaria infection. These plants may work as potential source in the development of variety of herbal formulations for malarial treatment.

  6. Chronic pharmacologic inhibition of EGFR leads to cardiac dysfunction in C57BL/6J mice

    International Nuclear Information System (INIS)

    Barrick, Cordelia J.; Yu Ming; Chao, H.-H.; Threadgill, David W.

    2008-01-01

    Molecule-targeted therapies like those against the epidermal growth factor receptor (EGFR) are becoming widely used in the oncology clinic. With improvements in treatment efficacy, many cancers are being treated as chronic diseases, with patients having prolonged exposure to several therapies that were previously only given acutely. The consequence of chronic suppression of EGFR activity may lead to unexpected toxicities like altered cardiac physiology, a common organ site for adverse drug effects. To explore this possibility, we treated C57BL/6J (B6) mice with two EGFR small molecule tyrosine kinase inhibitors (TKIs), irreversible EKB-569 and reversible AG-1478, orally for 3 months. In B6 female mice, chronic exposure to both TKIs depressed body weight gain and caused significant changes in left ventricular (LV) wall thickness and cardiac function. No significant differences were observed in heart weight or cardiomyocyte size but histological analysis revealed an increase in fibrosis and in the numbers of TUNEL-positive cells in the hearts from treated female mice. Consistent with histological results, LV apoptotic gene expression was altered, with significant downregulation of the anti-apoptotic gene Bcl2l1. Although there were no significant differences in any of these endpoints in treated male mice, suggesting sex may influence susceptibility to TKI mediated toxicity, the LVs of treated male mice had significant upregulation of Egf, Erbb2 and Nppb over controls. Taken together, these data suggest that chronic dietary exposure to TKIs may result in pathological and physiological changes in the heart

  7. Sofosbuvir based treatment of chronic hepatitis C genotype 3 infections

    DEFF Research Database (Denmark)

    Dalgard, Olav; Weiland, Ola; Noraberg, Geir

    2017-01-01

    BACKGROUND AND AIMS: Chronic hepatitis C virus (HCV) genotype 3 infection with advanced liver disease has emerged as the most challenging to treat. We retrospectively assessed the treatment outcome of sofosbuvir (SOF) based regimes for treatment of HCV genotype 3 infections in a real life setting...... in Scandinavia. METHODS: Consecutive patients with chronic HCV genotype 3 infection were enrolled at 16 treatment centers in Denmark, Sweden, Norway and Finland. Patients who had received a SOF containing regimen were included. The fibrosis stage was evaluated by liver biopsy or transient liver elastography...... was similar for all treatment regimens, but lower in men (p = 0.042), and in patients with decompensated liver disease (p = 0.004). CONCLUSION: We found that sofosbuvir based treatment in a real-life setting could offer SVR rates exceeding 90% in patients with HCV genotype 3 infection and advanced liver...

  8. Synthetic analogues of bovine bactenecin dodecapeptide reduce herpes simplex virus type 2 infectivity in mice

    DEFF Research Database (Denmark)

    Jenssen, Håvard; Shestakov, Andrey; Hancock, Robert E. W

    2013-01-01

    We have evaluated the potential of four synthetic peptides (denoted HH-2, 1002, 1006, 1018) with a distant relationship to the host defense peptide bovine bactenecin dodecapeptide for their ability to prevent genital infections with herpes simplex virus type 2 (HSV-2) in mice. All four peptides...... infectious doses of HSV-2. These data show that peptides HH-2 and 1018 have antiviral properties and can be used to prevent genital herpes infection in mice. (C) 2013 Elsevier B.V. All rights reserved....... was introduced in human semen. Two of the peptides proved especially effective in reducing HSV-2 infection also in vivo. When admixed with virus prior to inoculation, both HH-2 and 1018 reduced viral replication and disease development in a genital model of HSV-2 infection in mice, and also when using very high...

  9. Inflammatory stress promotes the development of obesity-related chronic kidney disease via CD36 in mice.

    Science.gov (United States)

    Yang, Ping; Xiao, Yayun; Luo, Xuan; Zhao, Yunfei; Zhao, Lei; Wang, Yan; Wu, Tingting; Wei, Li; Chen, Yaxi

    2017-07-01

    Ectopic fat located in the kidney has emerged as a novel cause of obesity-related chronic kidney disease (CKD). In this study, we aimed to investigate whether inflammatory stress promotes ectopic lipid deposition in the kidney and causes renal injury in obese mice and whether the pathological process is mediated by the fatty acid translocase, CD36. High-fat diet (HFD) feeding alone resulted in obesity, hyperlipidemia, and slight renal lipid accumulation in mice, which nevertheless had normal kidney function. HFD-fed mice with chronic inflammation had severe renal steatosis and obvious glomerular and tubular damage, which was accompanied by increased CD36 expression. Interestingly, CD36 deficiency in HFD-fed mice eliminated renal lipid accumulation and pathological changes induced by chronic inflammation. In both human mesangial cells (HMCs) and human kidney 2 (HK2) cells, inflammatory stress increased the efficiency of CD36 protein incorporation into membrane lipid rafts, promoting FFA uptake and intracellular lipid accumulation. Silencing of CD36 in vitro markedly attenuated FFA uptake, lipid accumulation, and cellular stress induced by inflammatory stress. We conclude that inflammatory stress aggravates renal injury by activation of the CD36 pathway, suggesting that this mechanism may operate in obese individuals with chronic inflammation, making them prone to CKD. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  10. A new model mimicking persistent HBV e antigen-negative infection using covalently closed circular DNA in immunocompetent mice.

    Directory of Open Access Journals (Sweden)

    Lei Wang

    Full Text Available Despite the availability of an effective vaccine, hepatitis B virus (HBV infection remains a major health problem. HBV e antigen (HBeAg-negative strains have become prevalent. Previously, no animal model mimicked the clinical course of HBeAg-negative HBV infection. To establish an HBeAg-negative HBV infection model, the 3.2-kb full-length genome of HBeAg-negative HBV was cloned from a clinical sample and then circularized to form covalently closed circular (cccDNA. The resulting cccDNA was introduced into the liver of C57BL/6J mice through hydrodynamic injection. Persistence of the HBeAg-negative infection was monitored at predetermined time points using HBV-specific markers including HBV surface antigen (HBsAg, HBeAg, and HBV core antigen (HBcAg as well as DNA copies. Throughout the study, pAAV-HBV1.2 was used as a control. In mice injected with HBeAg-negative cccDNA, the HBV infection rate was 100% at the initial stage. HBsAg levels increased up to 1 week, at which point levels peaked and dropped quickly thereafter. In 60% of injected mice, HBsAg and HBcAg persisted for more than 10 weeks. High numbers of HBV DNA copies were detected in the serum and liver. Moreover, cccDNA persisted in the liver tissue of HBeAg-negative mice. In contrast to the pAAV-HBV 1.2 injected mice, no HBeAg was found in mice injected with HBeAg-negative HBV throughout the study period. These results demonstrate the first successful establishment of a model of HBeAg-negative HBV-persistent infection in immunocompetent mice. Compared to pAAV-HBV1.2-injected mice, the infection persistence and levels of serum virological and biochemical markers were approximately equal in the model mice. This model will be useful for mechanistic studies on HBeAg-negative HBV infection and will facilitate the evaluation of new antiviral drugs.

  11. Morphine Tolerance and Physical Dependence Are Altered in Conditional HIV-1 Tat Transgenic Mice.

    Science.gov (United States)

    Fitting, Sylvia; Stevens, David L; Khan, Fayez A; Scoggins, Krista L; Enga, Rachel M; Beardsley, Patrick M; Knapp, Pamela E; Dewey, William L; Hauser, Kurt F

    2016-01-01

    Despite considerable evidence that chronic opiate use selectively affects the pathophysiologic consequences of human immunodeficiency virus type 1 (HIV-1) infection in the nervous system, few studies have examined whether neuro-acquired immune deficiency syndrome (neuroAIDS) might intrinsically alter the pharmacologic responses to chronic opiate exposure. This is an important matter because HIV-1 and opiate abuse are interrelated epidemics, and HIV-1 patients are often prescribed opiates as a treatment of HIV-1-related neuropathic pain. Tolerance and physical dependence are inevitable consequences of frequent and repeated administration of morphine. In the present study, mice expressing HIV-1 Tat in a doxycycline (DOX)-inducible manner [Tat(+)], their Tat(-) controls, and control C57BL/6 mice were chronically exposed to placebo or 75-mg morphine pellets to explore the effects of Tat induction on morphine tolerance and dependence. Antinociceptive tolerance and locomotor activity tolerance were assessed using tail-flick and locomotor activity assays, respectively, and physical dependence was measured with the platform-jumping assay and recording of other withdrawal signs. We found that Tat(+) mice treated with DOX [Tat(+)/DOX] developed an increased tolerance in the tail-flick assay compared with control Tat(-)/DOX and/or C57/DOX mice. Equivalent tolerance was developed in all mice when assessed by locomotor activity. Further, Tat(+)/DOX mice expressed reduced levels of physical dependence to chronic morphine exposure after a 1-mg/kg naloxone challenge compared with control Tat(-)/DOX and/or C57/DOX mice. Assuming the results seen in Tat transgenic mice can be generalized to neuroAIDS, our findings suggest that HIV-1-infected individuals may display heightened analgesic tolerance to similar doses of opiates compared with uninfected individuals and show fewer symptoms of physical dependence. Copyright © 2015 by The American Society for Pharmacology and Experimental

  12. Human hepatocyte depletion in the presence of HIV-1 infection in dual reconstituted humanized mice

    Science.gov (United States)

    Wang, Weimin; Cheng, Yan; Makarov, Edward; Ganesan, Murali; Gebhart, Catherine L.; Gorantla, Santhi; Osna, Natalia

    2018-01-01

    ABSTRACT Human immunodeficiency virus type 1 (HIV-1) infection impairs liver function, and liver diseases have become a leading cause of morbidity in infected patients. The immunopathology of liver damage caused by HIV-1 remains unclear. We used chimeric mice dually reconstituted with a human immune system and hepatocytes to address the relevance of the model to pathobiology questions related to human hepatocyte survival in the presence of systemic infection. TK-NOG males were transplanted with mismatched human hematopoietic stem/progenitor cells and hepatocytes, human albumin concentration and the presence of human immune cells in blood were monitored for hepatocytes and immune reconstitution, and mice were infected with HIV-1. HIV-1-infected animals showed a decline in human albumin concentration with a significant reduction in percentage of human hepatocytes compared to uninfected mice. The decrease in human albumin levels correlated with a decline in CD4+ cells in the liver and with an increase in HIV-1 viral load. HIV-1 infection elicited proinflammatory response in the immunological milieu of the liver in HIV-infected mice compared to uninfected animals, as determined by upregulation of IL23, CXCL10 and multiple toll-like receptor expression. The inflammatory reaction associated with HIV-1 infection in vivo could contribute to the depletion and dysfunction of hepatocytes. The dual reconstituted TK-NOG mouse model is a feasible platform to investigate hepatocyte-related HIV-1 immunopathogenesis. This article has an associated First Person interview with the first author of the paper. PMID:29361613

  13. Human hepatocyte depletion in the presence of HIV-1 infection in dual reconstituted humanized mice

    Directory of Open Access Journals (Sweden)

    Raghubendra Singh Dagur

    2018-02-01

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 infection impairs liver function, and liver diseases have become a leading cause of morbidity in infected patients. The immunopathology of liver damage caused by HIV-1 remains unclear. We used chimeric mice dually reconstituted with a human immune system and hepatocytes to address the relevance of the model to pathobiology questions related to human hepatocyte survival in the presence of systemic infection. TK-NOG males were transplanted with mismatched human hematopoietic stem/progenitor cells and hepatocytes, human albumin concentration and the presence of human immune cells in blood were monitored for hepatocytes and immune reconstitution, and mice were infected with HIV-1. HIV-1-infected animals showed a decline in human albumin concentration with a significant reduction in percentage of human hepatocytes compared to uninfected mice. The decrease in human albumin levels correlated with a decline in CD4+ cells in the liver and with an increase in HIV-1 viral load. HIV-1 infection elicited proinflammatory response in the immunological milieu of the liver in HIV-infected mice compared to uninfected animals, as determined by upregulation of IL23, CXCL10 and multiple toll-like receptor expression. The inflammatory reaction associated with HIV-1 infection in vivo could contribute to the depletion and dysfunction of hepatocytes. The dual reconstituted TK-NOG mouse model is a feasible platform to investigate hepatocyte-related HIV-1 immunopathogenesis. This article has an associated First Person interview with the first author of the paper.

  14. CD4 T Cell Responses in Latent and Chronic Viral Infections

    Science.gov (United States)

    Walton, Senta; Mandaric, Sanja; Oxenius, Annette

    2013-01-01

    The spectrum of tasks which is fulfilled by CD4 T cells in the setting of viral infections is large, ranging from support of CD8 T cells and humoral immunity to exertion of direct antiviral effector functions. While our knowledge about the differentiation pathways, plasticity, and memory of CD4 T cell responses upon acute infections or immunizations has significantly increased during the past years, much less is still known about CD4 T cell differentiation and their beneficial or pathological functions during persistent viral infections. In this review we summarize current knowledge about the differentiation, direct or indirect antiviral effector functions, and the regulation of virus-specific CD4 T cells in the setting of persistent latent or active chronic viral infections with a particular emphasis on herpes virus infections for the former and chronic lymphocytic choriomeningitis virus infection for the latter. PMID:23717308

  15. Effect of Acycloguanosine Treatment on Acute and Latent Herpes Simplex Infections in Mice

    Science.gov (United States)

    Field, Hugh J.; Bell, Susanne E.; Elion, Gertrude B.; Nash, Anthony A.; Wildy, Peter

    1979-01-01

    Systemic treatment of mice with the nucleoside analog 9-(2-hydroxyethoxymethyl)guanine (acycloguanosine [aciclovir]) was found to be highly effective against acute type 1 herpes simplex virus infection of the pinna. The drug ablated clinical signs and reduced virus replication both in tissue local to the inoculation site and within the nervous system. Provided that moderate-sized virus inocula were used, acycloguanosine treatment reduced or prevented the establishment of a latent infection in the dorsal root ganglia relating to the sensory nerve supply of the ear. However, although it aborted artificially produced infections in dorsal root ganglia, acycloguanosine was found not to be effective against the latent infection once established. This finding strongly indicated that latent herpes simplex virus in mice can exist in a nonreplicating form. PMID:464587

  16. Utility of humanized BLT mice for analysis of dengue virus infection and antiviral drug testing.

    Science.gov (United States)

    Frias-Staheli, Natalia; Dorner, Marcus; Marukian, Svetlana; Billerbeck, Eva; Labitt, Rachael N; Rice, Charles M; Ploss, Alexander

    2014-02-01

    Dengue virus (DENV) is the cause of a potentially life-threatening disease that affects millions of people worldwide. The lack of a small animal model that mimics the symptoms of DENV infection in humans has slowed the understanding of viral pathogenesis and the development of therapies and vaccines. Here, we investigated the use of humanized "bone marrow liver thymus" (BLT) mice as a model for immunological studies and assayed their applicability for preclinical testing of antiviral compounds. Human immune system (HIS) BLT-NOD/SCID mice were inoculated intravenously with a low-passage, clinical isolate of DENV-2, and this resulted in sustained viremia and infection of leukocytes in lymphoid and nonlymphoid organs. In addition, DENV infection increased serum cytokine levels and elicited DENV-2-neutralizing human IgM antibodies. Following restimulation with DENV-infected dendritic cells, in vivo-primed T cells became activated and acquired effector function. An adenosine nucleoside inhibitor of DENV decreased the circulating viral RNA when administered simultaneously or 2 days postinfection, simulating a potential treatment protocol for DENV infection in humans. In summary, we demonstrate that BLT mice are susceptible to infection with clinical DENV isolates, mount virus-specific adaptive immune responses, and respond to antiviral drug treatment. Although additional refinements to the model are required, BLT mice are a suitable platform to study aspects of DENV infection and pathogenesis and for preclinical testing of drug and vaccine candidates. IMPORTANCE Infection with dengue virus remains a major medical problem. Progress in our understanding of the disease and development of therapeutics has been hampered by the scarcity of small animal models. Here, we show that humanized mice, i.e., animals engrafted with components of a human immune system, that were infected with a patient-derived dengue virus strain developed clinical symptoms of the disease and mounted

  17. Poliovirus mutants excreted by a chronically infected hypogammaglobulinemic patient establish persistent infections in human intestinal cells

    International Nuclear Information System (INIS)

    Labadie, Karine; Pelletier, Isabelle; Saulnier, Aure; Martin, Javier; Colbere-Garapin, Florence

    2004-01-01

    Immunodeficient patients whose gut is chronically infected by vaccine-derived poliovirus (VDPV) may excrete large amounts of virus for years. To investigate how poliovirus (PV) establishes chronic infections in the gut, we tested whether it is possible to establish persistent VDPV infections in human intestinal Caco-2 cells. Four type 3 VDPV mutants, representative of the viral evolution in the gut of a hypogammaglobulinemic patient over almost 2 years [J. Virol. 74 (2000) 3001], were used to infect both undifferentiated, dividing cells, and differentiated, polarized enterocytes. A VDPV mutant excreted 36 days postvaccination by the patient was lytic in both types of intestinal cell cultures, like the parental Sabin 3 (S3) strain. In contrast, three VDPVs excreted 136, 442, and 637 days postvaccination, established persistent infections both in undifferentiated cells and in enterocytes. Thus, viral determinants selected between day 36 and 136 conferred on VDPV mutants the capacity to infect intestinal cells persistently. The percentage of persistently VDPV-infected cultures was higher in enterocytes than in undifferentiated cells, implicating cellular determinants involved in the differentiation of enterocytes in persistent VDPV infections. The establishment of persistent infections in enterocytes was not due to poor replication of VDPVs in these cells, but was associated with reduced viral adsorption to the cell surface

  18. Time course of gene expression profiling in the liver of experimental mice infected with Echinococcus multilocularis.

    Directory of Open Access Journals (Sweden)

    Renyong Lin

    Full Text Available BACKGROUND: Alveolar echinococcosis (AE is a severe chronic parasitic disease which behaves like a slow-growing liver cancer. Clinical observations suggest that the parasite, Echinococcus multilocularis (E. multilocularis influences liver homeostasis and hepatic cell metabolism. However, this has never been analyzed during the time course of infection in the common model of secondary echinococcosis in experimental mice. METHODOLOGY/PRINCIPAL FINDINGS: Gene expression profiles were assessed using DNA microarray analysis, 1, 2, 3 and 6 months after injection of E. multilocularis metacestode in the liver of susceptible mice. Data were collected at different time points to monitor the dynamic behavior of gene expression. 557 differentially expressed genes were identified at one or more time points, including 351 up-regulated and 228 down-regulated genes. Time-course analysis indicated, at the initial stage of E. multilocularis infection (month 1-2, that most of up-regulated pathways were related to immune processes and cell trafficking such as chemokine-, mitogen-activated protein kinase (MAPK signaling, and down-regulated pathways were related to xenobiotic metabolism; at the middle stage (month 3, MAPK signaling pathway was maintained and peroxisome proliferator-activated receptor (PPAR signaling pathway emerged; at the late stage (month 6, most of up-regulated pathways were related to PPAR signaling pathway, complement and coagulation cascades, while down-regulated pathways were related to metabolism of xenobiotics by cytochrome P450. Quantitative RT-PCR analysis of a random selection of 19 genes confirmed the reliability of the microarray data. Immunohistochemistry analysis showed that proliferating cell nuclear antigen (PCNA was increased in the liver of E. multilocularis infected mice from 2 months to 6 months. CONCLUSIONS: E. multilocularis metacestode definitely exerts a deep influence on liver homeostasis, by modifying a number of gene

  19. Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing Clostridium difficile disease in mice.

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    Trevor D Lawley

    Full Text Available Relapsing C. difficile disease in humans is linked to a pathological imbalance within the intestinal microbiota, termed dysbiosis, which remains poorly understood. We show that mice infected with epidemic C. difficile (genotype 027/BI develop highly contagious, chronic intestinal disease and persistent dysbiosis characterized by a distinct, simplified microbiota containing opportunistic pathogens and altered metabolite production. Chronic C. difficile 027/BI infection was refractory to vancomycin treatment leading to relapsing disease. In contrast, treatment of C. difficile 027/BI infected mice with feces from healthy mice rapidly restored a diverse, healthy microbiota and resolved C. difficile disease and contagiousness. We used this model to identify a simple mixture of six phylogenetically diverse intestinal bacteria, including novel species, which can re-establish a health-associated microbiota and clear C. difficile 027/BI infection from mice. Thus, targeting a dysbiotic microbiota with a defined mixture of phylogenetically diverse bacteria can trigger major shifts in the microbial community structure that displaces C. difficile and, as a result, resolves disease and contagiousness. Further, we demonstrate a rational approach to harness the therapeutic potential of health-associated microbial communities to treat C. difficile disease and potentially other forms of intestinal dysbiosis.

  20. Gene Expression Profile in the Liver of BALB/c Mice Infected with Fasciola hepatica.

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    Jose Rojas-Caraballo

    Full Text Available Fasciola hepatica infection still remains one of the helminthic neglected tropical diseases (NTDs. It has a huge worldwide distribution, affecting mainly cattle and, sometimes, human beings. In addition to data reported about the immunological response induced by helminthic infections and that induced by Fasciola hepatica, little is known about the gene expression profile in its organ target, the liver, which is where adult worms are established and live for long periods of time, causing its characteristic pathology. In the present work, we study both the early and late gene expression profiles in the livers of mice infected with F. hepatica metacercariae using a microarray-based methodology.A total of 9 female-6-week-old BALB/c mice (Charles River Laboratories, Barcelona, Spain weighing 20 to 35 g were used for the experiments. Two groups of BALB/c mice were orally infected with seven F. hepatica metacercariae, and the other group remained untreated and served as a control. Mice were humanely euthanized and necropsied for liver recovery, histological assessment of hepatic damage, RNA isolation, microarray design and gene expression analysis on the day of infection (t0, seven days post-infection (t7 and twenty-one days post-infection (t21.We found that F. hepatica infection induces the differential expression of 128 genes in the liver in the early stage of infection and 308 genes in the late stage, and most of them are up-regulated. The Ingenuity Pathway Analysis revealed significant changes in the pathways related to metabolism, biosynthesis and signaling as well as genes implicated in inducing liver-toxicity, injury and death.The present study provides us insights at the molecular level about the underlying mechanisms used by F. hepatica, leading to liver damage and its subsequent pathophysiology. The expression pattern obtained here could also be used to explain the lack of association between infection with F. hepatica and cholangiocarcinoma

  1. Gene Expression Profile in the Liver of BALB/c Mice Infected with Fasciola hepatica.

    Science.gov (United States)

    Rojas-Caraballo, Jose; López-Abán, Julio; Fernández-Soto, Pedro; Vicente, Belén; Collía, Francisco; Muro, Antonio

    2015-01-01

    Fasciola hepatica infection still remains one of the helminthic neglected tropical diseases (NTDs). It has a huge worldwide distribution, affecting mainly cattle and, sometimes, human beings. In addition to data reported about the immunological response induced by helminthic infections and that induced by Fasciola hepatica, little is known about the gene expression profile in its organ target, the liver, which is where adult worms are established and live for long periods of time, causing its characteristic pathology. In the present work, we study both the early and late gene expression profiles in the livers of mice infected with F. hepatica metacercariae using a microarray-based methodology. A total of 9 female-6-week-old BALB/c mice (Charles River Laboratories, Barcelona, Spain) weighing 20 to 35 g were used for the experiments. Two groups of BALB/c mice were orally infected with seven F. hepatica metacercariae, and the other group remained untreated and served as a control. Mice were humanely euthanized and necropsied for liver recovery, histological assessment of hepatic damage, RNA isolation, microarray design and gene expression analysis on the day of infection (t0), seven days post-infection (t7) and twenty-one days post-infection (t21). We found that F. hepatica infection induces the differential expression of 128 genes in the liver in the early stage of infection and 308 genes in the late stage, and most of them are up-regulated. The Ingenuity Pathway Analysis revealed significant changes in the pathways related to metabolism, biosynthesis and signaling as well as genes implicated in inducing liver-toxicity, injury and death. The present study provides us insights at the molecular level about the underlying mechanisms used by F. hepatica, leading to liver damage and its subsequent pathophysiology. The expression pattern obtained here could also be used to explain the lack of association between infection with F. hepatica and cholangiocarcinoma. However

  2. Clinical Holistic Medicine: Chronic Infections and Autoimmune Diseases

    OpenAIRE

    Ventegodt, Søren; Merrick, Joav

    2005-01-01

    The consciousness-based (holistic) medical toolbox might be useful in general practice and in cases of recurrent infections and chronic infection or inflammation. From our clinical experiences, there is hope for improvement from a number of diseases caused by disorders affecting the regulation of the immune system when the physician includes the holistic medical approach.Our scientific understanding of the connection between consciousness and cellular order is still limited. Consciousness-bas...

  3. Post-splenectomy infections in chronic schistosomiasis as a consequence of bacterial translocation

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    Kedma de Magalhães Lima

    2015-06-01

    Full Text Available INTRODUCTION : Bacterial translocation is the invasion of indigenous intestinal bacteria through the gut mucosa to normally sterile tissues and internal organs. Schistosomiasis may cause alterations in the immune system and damage to the intestines, portal system and mesenteric lymph nodes. This study investigated bacterial translocation and alterations in the intestinal microbiota and mucosa in schistosomiasis and splenectomized mice. METHODS : Forty female 35-day-old Swiss Webster mice were divided into the following four groups with 10 animals each: schistosomotic (ESF, splenectomized schistosomotic (ESEF, splenectomized (EF and control (CF. Infection was achieved by introduction of 50 Schistosoma mansoni (SLM cercariae through the skin. At 125 days after birth, half of the parasitized and unparasitized mice were subjected to splenectomy. Body weights were recorded for one week after splenectomy; then, the mice were euthanized to study bacterial translocation, microbiota composition and intestinal morphometry. RESULTS : We observed significant reductions in the weight increases in the EF, ESF and ESEF groups. There were increases of at least 1,000 CFU of intestinal microbiota bacteria in these groups compared with the CF. The EF, ESF and ESEF mice showed decreases in the heights and areas of villi and the total villus areas (perimeter. We observed frequent co-infections with various bacterial genera. CONCLUSIONS : The ESEF mice showed a higher degree of sepsis. This finding may be associated with a reduction in the immune response associated with the absence of the spleen and a reduction in nutritional absorption strengthened by both of these factors (Schistosoma infection and splenectomy.

  4. Immune response in mice infected with Candida albicans in the mycelial form.

    Science.gov (United States)

    Bibas Bonet de Jorrat, M E; de Valdez, G A; de Petrino, S F; Sirena, A; Perdigón, G

    1989-05-01

    The effect of the infection with the mycelial form of a Candida albicans strain (Mycology Dept.) upon the immune system in mice was studied. BALB/c mice were infected intraperitoneally in a single dose of a 3 x 10(6), 6 x 10(6) and 12 x 10(6) cell suspension of the strain. Macrophages's activity was studied the days 7, 14, 21, 28, 35, and 42 after inoculation, by the following assays: phagocytosis in vitro, mononucleated phagocytic system by the colloidal carbon clearance technique, the lymphocyte's activity by the direct plaque forming cells technique (PFC) and delayed hypersensitivity (DTH). Infection with the mycelial form did not affect the peritoneal macrophage's phagocytic ability, neither modified the delayed hypersensitivity to sheep red blood cells (SRBC). However, a slight and transient depression of the lymphocyte stimulation was found. Suppression of PFC to SRBC was high when a 12 x 10(6) cell suspension was used in contrast to the infection with blastospores. These results suggest that systemic infection by Candida albicans in its mycelial form do not induce a non specific immunosuppression.

  5. Vaccine-mediated immune responses to experimental pulmonary Cryptococcus gattii infection in mice.

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    Ashok K Chaturvedi

    Full Text Available Cryptococcus gattii is a fungal pathogen that can cause life-threatening respiratory and disseminated infections in immune-competent and immune-suppressed individuals. Currently, there are no standardized vaccines against cryptococcosis in humans, underlying an urgent need for effective therapies and/or vaccines. In this study, we evaluated the efficacy of intranasal immunization with C. gattii cell wall associated (CW and/or cytoplasmic (CP protein preparations to induce protection against experimental pulmonary C. gattii infection in mice. BALB/c mice immunized with C. gattii CW and/or CP protein preparations exhibited a significant reduction in pulmonary fungal burden and prolonged survival following pulmonary challenge with C. gattii. Protection was associated with significantly increased pro-inflammatory and Th1-type cytokine recall responses, in vitro and increased C. gattii-specific antibody production in immunized mice challenged with C. gattii. A number of immunodominant proteins were identified following immunoblot analysis of C. gattii CW and CP protein preparations using sera from immunized mice. Immunization with a combined CW and CP protein preparation resulted in an early increase in pulmonary T cell infiltrates following challenge with C. gattii. Overall, our studies show that C. gattii CW and CP protein preparations contain antigens that may be included in a subunit vaccine to induce prolonged protection against pulmonary C. gattii infection.

  6. Unconventional Pro-inflammatory CD4+ T Cell Response in B Cell-Deficient Mice Infected with Trypanosoma cruzi

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    Melisa Gorosito Serrán

    2017-11-01

    Full Text Available Chagas disease, caused by the parasite Trypanosoma cruzi, is endemic in Latin America but has become a global public health concern by migration of infected people. It has been reported that parasite persistence as well as the intensity of the inflammatory immune response are determinants of the clinical manifestations of the disease. Even though inflammation is indispensable for host defense, when deregulated, it can contribute to tissue injury and organ dysfunction. Here, we report the importance of B cells in conditioning T cell response in T. cruzi infection. Mice deficient in mature B cells (muMT mice infected with T. cruzi exhibited an increase in plasma TNF concentration, TNF-producing CD4+ T cells, and mortality. The increase in TNF-producing CD4+ T cells was accompanied by a reduction in IFNγ+CD4+ T cells and a decrease of the frequency of regulatory Foxp3+, IL-10+, and IL17+CD4+ T cells populations. The CD4+ T cell population activated by T. cruzi infection, in absence of mature B cells, had a high frequency of Ly6C+ cells and showed a lower expression of inhibitory molecules such as CTLA-4, PD-1, and LAG3. CD4+ T cells from infected muMT mice presented a high frequency of CD62LhiCD44− cells, which is commonly associated with a naïve phenotype. Through transfer experiments we demonstrated that CD4+ T cells from infected muMT mice were able to condition the CD4+ T cells response from infected wild-type mice. Interestingly, using Blimp-flox/flox-CD23icre mice we observed that in absence of plasmablast/plasma cell T. cruzi-infected mice exhibited a higher number of TNF-producing CD4+ T cells. Our results showed that the absence of B cells during T. cruzi infection affected the T cell response at different levels and generated a favorable scenario for unconventional activation of CD4+ T cell leading to an uncontrolled effector response and inflammation. The product of B cell differentiation, the plasmablast/plasma cells, could be able

  7. Reduction of Influenza Virus Titer and Protection against Influenza Virus Infection in Infant Mice Fed Lactobacillus casei Shirota

    OpenAIRE

    Yasui, Hisako; Kiyoshima, Junko; Hori, Tetsuji

    2004-01-01

    We investigated whether oral administration of Lactobacillus casei strain Shirota to neonatal and infant mice ameliorates influenza virus (IFV) infection in the upper respiratory tract and protects against influenza infection. In a model of upper respiratory IFV infection, the titer of virus in the nasal washings of infant mice administered L. casei Shirota (L. casei Shirota group) was significantly (P < 0.05) lower than that in infant mice administered saline (control group) (102.48 ± 100.31...

  8. Chronic Pelvic Pain Development and Prostate Inflammation in Strains of Mice With Different Susceptibility to Experimental Autoimmune Prostatitis.

    Science.gov (United States)

    Breser, Maria L; Motrich, Ruben D; Sanchez, Leonardo R; Rivero, Virginia E

    2017-01-01

    Experimental autoimmune prostatitis (EAP) is an autoimmune inflammatory disease of the prostate characterized by peripheral prostate-specific autoimmune responses associated with prostate inflammation. EAP is induced in rodents upon immunization with prostate antigens (PAg) plus adjuvants and shares important clinical and immunological features with the human disease chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). EAP was induced in young NOD, C57BL/6, and BALB/c male mice by immunization with PAg plus complete Freund́s adjuvant. Tactile allodynia was assessed using Von Frey fibers as a measure of pelvic pain at baseline and at different time points after immunization. Using conventional histology, immunohistochemistry, FACS analysis, and protein arrays, an interstrain comparative study of prostate cell infiltration and inflammation was performed. Chronic pelvic pain development was similar between immunized NOD and C57BL/6 mice, although the severity of leukocyte infiltration was greater in the first case. Coversely, minimal prostate cell infiltration was observed in immunized BALB/c mice, who showed no pelvic pain development. Increased numbers of mast cells, mostly degranulated, were detected in prostate samples from NOD and C57BL/6 mice, while lower total counts and resting were observed in BALB/c mice. Prostate tissue from NOD mice revealed markedly increased expression levels of inflammatory cytokines, chemokines, adhesion molecules, vascular endothelial growth factor, and metalloproteinases. Similar results, but to a lesser extent, were observed when analyzing prostate tissue from C57BL/6 mice. On the contrary, the expression of the above mediators was very low in prostate tissue from immunized BALB/c mice, showing significantly slight increments only for CXCL1 and IL4. Our results provide new evidence indicating that NOD, C57BL/6, and BALB/c mice develop different degrees of chronic pelvic pain, type, and amount of prostate cell infiltration

  9. Chronic Pseudomonas aeruginosa lung infection in normal and athymic rats

    DEFF Research Database (Denmark)

    Johansen, H K; Espersen, F; Pedersen, S S

    1993-01-01

    We have compared a chronic lung infection with Pseudomonas aeruginosa embedded in alginate beads in normal and athymic rats with an acute infection with free live P. aeruginosa bacteria. The following parameters were observed and described: mortality, macroscopic and microscopic pathologic changes...

  10. The effect of centaurein on interferon-γ expression and Listeria infection in mice

    International Nuclear Information System (INIS)

    Chang, S.-L.; Yeh, H.-H.; Lin, Y.-S.; Chiang, Y.-M.; Wu, T.-K.; Yang, W.-C.

    2007-01-01

    We previously found that centaurein enhanced IFN-γ transcription in T cells. Here, we demonstrate that centaurein increased the IFN-γ expression in T and NK cells and the serum IFN-γ level in mice. Centaurein elevated the transcription of T-bet but not GATA-3, which is consistent with its effect on that of IFN-γ but not IL-4. Additionally, centaurein effectively protected mice against Listeria infection. Moreover, centaurein per se or in combination with antibiotics could treat Listeria infection. Our mechanistic studies suggest that centaurein augments IFN-γ expression via a transcriptional up-regulation of T-bet and that centaurein protects against or treats Listeria infection via a modulation of IFN-γ expression

  11. Anti-soluble liver antigen (SLA) antibodies in chronic HCV infection.

    Science.gov (United States)

    Vitozzi, Susana; Lapierre, Pascal; Djilali-Saiah, Idriss; Marceau, Gabriel; Beland, Kathie; Alvarez, Fernando

    2004-05-01

    Hepatitis C infection is associated with autoimmune disorders, such as the production of autoantibodies. Anti-LKM1 and anti-LC1, immunomarkers of type 2 autoimmune hepatitis, have been previously associated with a HCV infection. Anti-Soluble-Liver-Antigen autoantibodies (SLA) are specifically associated with type 1 and type 2 autoimmune hepatitis and more closely related to patients who relapse after steroid therapy. The recent molecular cloning of the soluble liver antigen provides the opportunity to develop more specific tests for the detection of antibodies against it. The aim of this work is to characterize anti-soluble-liver autoantibodies in sera from patients chronically infected by HCV. A recombinant cDNA from activated Jurkat cells coding for the full length tRNP(Ser)Sec/SLA antigen was obtained. ELISA, Western Blot and immunoprecipitation tests were developed and used to search for linear and conformational epitopes recognized by anti-SLA antibodies in sera from patients chronically infected by HCV. Anti-soluble liver antigen antibodies were found in sera from 10.4% of HCV-infected patients. The prevalence was significantly increased to 27% when anti-LKM1 was also present. Most anti-SLA reactivity was directed against conformational epitopes on the antigen. The means titers by ELISA were lower than those obtained in type 2 AIH. The result of autoantibody isotyping showed a subclass restriction to IgG1 and also IgG4. This study shows the presence of anti-SLA antibodies in approximately 10% of HCV infected patients. The prevalence of SLA autoantibodies in HCV infected patients increases when LKM1 autoantibodies are also present. The relationship between the prevalence of this characteristic autoimmune hepatitis autoantibody and the implication of an autoimmune phenomenon in the liver injury of patients chronically infected by HCV needs further investigation.

  12. Helicobacter pylori infection induces genetic instability of nuclear and mitochondrial DNA in gastric cells

    DEFF Research Database (Denmark)

    Machado, Ana Manuel Dantas; Figueiredo, Ceu; Touati, Eliette

    2009-01-01

    of genetic instabilities in the nuclear and mitochondrial DNA (mtDNA) were examined. EXPERIMENTAL DESIGN: We observed the effects of H. pylori infection on a gastric cell line (AGS), on C57BL/6 mice, and on individuals with chronic gastritis. In AGS cells, the effect of H. pylori infection on base excision...... cells and chronic gastritis tissue were determined by PCR, single-stranded conformation polymorphism, and sequencing. H. pylori vacA and cagA genotyping was determined by multiplex PCR and reverse hybridization. RESULTS: Following H. pylori infection, the activity and expression of base excision repair...... and MMR are down-regulated both in vitro and in vivo. Moreover, H. pylori induces genomic instability in nuclear CA repeats in mice and in mtDNA of AGS cells and chronic gastritis tissue, and this effect in mtDNA is associated with bacterial virulence. CONCLUSIONS: Our results suggest that H. pylori...

  13. Polymicrobial infection with major periodontal pathogens induced periodontal disease and aortic atherosclerosis in hyperlipidemic ApoE(null mice.

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    Mercedes F Rivera

    Full Text Available Periodontal disease (PD and atherosclerosis are both polymicrobial and multifactorial and although observational studies supported the association, the causative relationship between these two diseases is not yet established. Polymicrobial infection-induced periodontal disease is postulated to accelerate atherosclerotic plaque growth by enhancing atherosclerotic risk factors of orally infected Apolipoprotein E deficient (ApoE(null mice. At 16 weeks of infection, samples of blood, mandible, maxilla, aorta, heart, spleen, and liver were collected, analyzed for bacterial genomic DNA, immune response, inflammation, alveolar bone loss, serum inflammatory marker, atherosclerosis risk factors, and aortic atherosclerosis. PCR analysis of polymicrobial-infected (Porphyromonas gingivalis [P. gingivalis], Treponema denticola [T. denticola], and Tannerella forsythia [T. forsythia] mice resulted in detection of bacterial genomic DNA in oral plaque samples indicating colonization of the oral cavity by all three species. Fluorescent in situ hybridization detected P. gingivalis and T. denticola within gingival tissues of infected mice and morphometric analysis showed an increase in palatal alveolar bone loss (p<0.0001 and intrabony defects suggesting development of periodontal disease in this model. Polymicrobial-infected mice also showed an increase in aortic plaque area (p<0.05 with macrophage accumulation, enhanced serum amyloid A, and increased serum cholesterol and triglycerides. A systemic infection was indicated by the detection of bacterial genomic DNA in the aorta and liver of infected mice and elevated levels of bacterial specific IgG antibodies (p<0.0001. This study was a unique effort to understand the effects of a polymicrobial infection with P. gingivalis, T. denticola and T. forsythia on periodontal disease and associated atherosclerosis in ApoE(null mice.

  14. Effects of adding ribavirin to interferon to treat chronic hepatitis C infection

    DEFF Research Database (Denmark)

    Brok, Jesper; Gluud, Lise L; Gluud, Christian

    2005-01-01

    Evidence shows that a combination therapy of ribavirin plus interferon clears hepatitis C virus from the blood in about 40% of patients with chronic hepatitis C infection, but the effects on clinical outcomes are unclear. We evaluated the beneficial and harmful effects of ribavirin plus interferon...... vs interferon alone for treatment of patients with chronic hepatitis C infection. Randomized trials were included irrespective of blinding, language, or publication status. Trials were identified through the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Library, MEDLINE....... In conclusion, the effect of ribavirin plus interferon on viral clearance may lead to reduced mortality and morbidity in patients with chronic hepatitis C infection. However, combination therapy is associated with increased risk for adverse events....

  15. Nucleotide-Binding Oligomerization Domain-1 and -2 Play No Role in Controlling Brucella abortus Infection in Mice

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    Fernanda S. Oliveira

    2012-01-01

    Full Text Available Nucleotide-binding oligomerization domain proteins (NODs are modular cytoplasmic proteins implicated in the recognition of peptidoglycan-derived molecules. Further, several in vivo studies have demonstrated a role for Nod1 and Nod2 in host defense against bacterial pathogens. Here, we demonstrated that macrophages from NOD1-, NOD2-, and Rip2-deficient mice produced lower levels of TNF-α following infection with live Brucella abortus compared to wild-type mice. Similar reduction on cytokine synthesis was not observed for IL-12 and IL-6. However, NOD1, NOD2, and Rip2 knockout mice were no more susceptible to infection with virulent B. abortus than wild-type mice. Additionally, spleen cells from NOD1-, NOD2-, and Rip2-deficient mice showed unaltered production of IFN-γ compared to C57BL/6 mice. Taken together, this study demonstrates that NOD1, NOD2 and Rip2 are dispensable for the control of B. abortus during in vivo infection.

  16. [Efficacy of albendazole chitosan microspheres against Echinococcus granulosus infection in mice].

    Science.gov (United States)

    Liang, Wen; Wang, Xin-Chun; Wu, Xiang-Wei; Zhang, Shi-Jie; Sun, Hong; Ma, Xin; Peng, Xin-Yu

    2014-06-01

    To observe the therapeutic effect of albendazole chitosan microspheres (ABZ-CS-MPs) on cystic echinococcosis in mice. Two hundred male kunming mice were each infected by intraperitoneal inoculation of about 5 000 viable protoscoleces of Echinococcus granulosus. Another 20 mice were kept as blank control. After 12 weeks post infection, the mice were randomly divided into four groups named as infection control group (n = 20), ABZ-CS-MPs group, albendazole liposome (L-ABZ) group, and albendazole tablet group. The latter three treatment groups were then each divided into three subgroups (n = 20) by given the dose of 37.5, 75.0, and 150.0 mg/kg for three times per week, respectively. After 12 weeks of treatment, all mice were sacrificed. The weight of hydatid cysts was measured and the inhibition rate were calculated. Mouse liver was observed. The histopathological changes of E. granulosus were observed by microscopy. The concentration of albendazole sulfoxide in plasma and liver tissues was determined by high-performance liquid chromatography. Compared with the other treatment groups, the turbidity of contained fluid, the consolidation level and calcification level of hydatid cysts in ABZ-CS-MPs group were higher. The average weight of hydatid cysts in each treatment group was lower than that of infection control group [(3.19 +/- 2.94) g] (P albendazole tablet groups [(0.77 +/- 0.74), (0.55 +/- 0.42), (0.76 +/- 0.35) g] (P albendazole tablet group (Palbendazole sulfoxide in 75.0 and 150.0 mg/kg ABZ-CS-MPs sub-groups [(0.83 +/- 0.39), (0.80 +/- 0.5) microg/ml] were higher than that of L-ABZ sub-groups [(0.34 +/- 0.03), (0.43 +/- 0.15) microg/ml] and albendazole tablet sub-groups [(0.31 +/- 0.02), (0.40 +/- 0.10) microg/ml] (P albendazole tablet sub-groups [(0.04 +/- 0.02), (0.07 +/- 0.04), (0.04 +/- 0.0) microg/g], the albendazole sulfoxide concentration in liver tissue was higher in ABZ-CS-MPs sub-groups [(0.33 +/- 0.06), (0.45 +/- 0.31), (0.50 +/- 0.30) microg/g] (P

  17. Hepatitis virus infection and chronic liver disease among atomic-bomb survivors

    International Nuclear Information System (INIS)

    Fujiwara, Saeko; Cologne, John; Akahoshi, Masazumi; Kusumi, Shizuyo; Kodama, Kazunori; Yoshizawa, Hiroshi

    2000-01-01

    Hepatitis C and B virus (HCV, HBV) infection plays a crucial role in the etiology of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma, which have been reported to increase with radiation dose among the atomic bomb survivors. The purpose of this study is to investigate whether radiation exposure altered the prevalence of hepatitis virus infection or accelerated the progress toward chronic hepatitis after hepatitis virus infection. Levels of serum antibody to hepatitis C virus (anti-HCV), HBs antigen (HBsAg), and anti-HBs antibody (anti-HBs) were measured for 6,121 participants in the Adult Health Study of atomic bomb survivors in Hiroshima and Nagasaki. No relationship was found between anti-HCV prevalence and radiation dose, after adjusting for age, sex, city, history of blood transfusion, acupuncture, and family history, but prevalence of anti-HCV was significantly lower overall among the radiation-exposed people (relative prevalence 0.84, p=0.022) compared to people with estimated radiation dose 0 Gy. No significant interaction was found between any of the above mentioned risk factors and radiation dose. People with anti-HCV positive had 13 times higher prevalence of chronic liver disease than those without anti-HCV. However, the radiation dose response for chronic liver disease among anti-HCV positive survivors may be greater than that among anti-HCV negative survivors (slope ratio 20), but the difference was marginally significant (p=0.097). Prevalence of HBsAg increased with whole-body kerma. However, no trend with radiation dose was found in the anti-HBs prevalence. In the background, prevalence of chronic liver disease in people with HBsAg-positive was approximately three times higher that in those without HBsAg. No difference in slope of the dose was found among HBsAg positive and negative individuals (slope: HBsAg positive 0.91/Gy, HBsAg negative 0.11/Gy, difference p=0.66). In conclusion, no dose-response relationship was found between

  18. Hepatitis virus infection and chronic liver disease among atomic-bomb survivors

    Energy Technology Data Exchange (ETDEWEB)

    Fujiwara, Saeko; Cologne, John; Akahoshi, Masazumi [Radiation Effects Research Foundation, Hiroshima (Japan); Kusumi, Shizuyo [Institute of Radiation Epidemiology, Radiation Effects Association, Tokyo (Japan); Kodama, Kazunori; Yoshizawa, Hiroshi [Hiroshima University School of Medicine, Hiroshima (Japan)

    2000-05-01

    Hepatitis C and B virus (HCV, HBV) infection plays a crucial role in the etiology of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma, which have been reported to increase with radiation dose among the atomic bomb survivors. The purpose of this study is to investigate whether radiation exposure altered the prevalence of hepatitis virus infection or accelerated the progress toward chronic hepatitis after hepatitis virus infection. Levels of serum antibody to hepatitis C virus (anti-HCV), HBs antigen (HBsAg), and anti-HBs antibody (anti-HBs) were measured for 6,121 participants in the Adult Health Study of atomic bomb survivors in Hiroshima and Nagasaki. No relationship was found between anti-HCV prevalence and radiation dose, after adjusting for age, sex, city, history of blood transfusion, acupuncture, and family history, but prevalence of anti-HCV was significantly lower overall among the radiation-exposed people (relative prevalence 0.84, p=0.022) compared to people with estimated radiation dose 0 Gy. No significant interaction was found between any of the above mentioned risk factors and radiation dose. People with anti-HCV positive had 13 times higher prevalence of chronic liver disease than those without anti-HCV. However, the radiation dose response for chronic liver disease among anti-HCV positive survivors may be greater than that among anti-HCV negative survivors (slope ratio 20), but the difference was marginally significant (p=0.097). Prevalence of HBsAg increased with whole-body kerma. However, no trend with radiation dose was found in the anti-HBs prevalence. In the background, prevalence of chronic liver disease in people with HBsAg-positive was approximately three times higher that in those without HBsAg. No difference in slope of the dose was found among HBsAg positive and negative individuals (slope: HBsAg positive 0.91/Gy, HBsAg negative 0.11/Gy, difference p=0.66). In conclusion, no dose-response relationship was found between

  19. Routine one-stage exchange for chronic infection after total hip replacement.

    Science.gov (United States)

    Jenny, Jean-Yves; Lengert, Régis; Diesinger, Yann; Gaudias, Jeannot; Boeri, Cyril; Kempf, Jean-François

    2014-12-01

    We hypothesized that a routine one-stage exchange for treatment of chronically infected total hip replacement (THR) will lead to (1) a higher rate of infection recurrence and (2) a poorer hip outcome than the published rates after two-stage exchange. Sixty-five cases have been treated consecutively with one-stage exchange. All patients have been followed for a period of three to six years or until death or infection recurrence. The five-year rate for infection recurrence was 16%. The five-year survival rate for recurrence of the index infection was 8%. Forty-two percent of the hips had a good or excellent PMA score, and 46% a good or excellent OH score. Routine one-stage exchange was not associated with a higher recurrence rate and a poorer hip function than previously published series of two-stage exchange. Therefore, there is little support to choose two-stage exchange as the routine treatment for management of chronically infected THR.

  20. Impaired Thymic Output in Patients with Chronic Hepatitis C Virus Infection

    DEFF Research Database (Denmark)

    Hartling, Hans Jakob; Gaardbo, Julie Christine; Ronit, Andreas

    2013-01-01

    Altered T cell homeostasis in chronic hepatitis C virus (HCV) infection has been demonstrated. However, it is unknown if fibrosis is associated with more perturbed T cell homeostasis in chronic HCV infection. The aim of the present study was to examine and compare T cell subsets including recent...... thymic emigrants (RTE), naive, memory, senescent, apoptotic and IL-7 receptor α (CD127) expressing CD4+ and CD8+ T cells as well as telomere length and interferon-γ production in HCV-infected patients with (n=25) and without (n=26) fibrosis as well as in healthy controls (n=24). Decreased proportions...... of CD4+ and CD8+ RTE were found in HCV-infected patients, especially in HCV-infected patients with fibrosis (14.3% (9.7-23.0) and 28.8% (16.1-40.5), respectively) compared to healthy controls (24.2% (16.3-32.1), P=0.004, and 39.1% (31.6-55.0), P=0.010, respectively). Furthermore, HCV-infected patients...

  1. Cytokine profile and natural killer cell activity in Listeria monocytogenes infected mice treated orally with Petiveria alliacea extract.

    Science.gov (United States)

    Queiroz, M L; Quadros, M R; Santos, L M

    2000-08-01

    In this work, we investigated the effects of Petiveria alliacea extract on the production of Th1-type and Th2-type cytokines and on NK cells activity in normal and Listeria monocytogenes infected mice. Our results demonstrated that in normal/non-infected mice P. alliacea administration led to increased levels of Interleukin-2 (IL-2). The infection alone enhanced INF-gamma levels and NK cell activity at 48 and 72 hours of infection. The treatment with five consecutive doses of 1000 mg/kg/day of P. alliacea extract, given previously to infection, led to further increases in IL-2 levels, in relation to normal/non-infected/P. alliacea treated controls, and in INF-gamma levels at 72 h of infection, compared to infected mice. On the other hand, the production of IL-4 and IL-10 were not altered either by the infection or by the treatment with P. alliacea extract. NK cells activity increased at 48 h and 72 h following the inoculation of the bacteria. When mice were treated with P. alliacea previously to infection, NK activity was higher than that observed at 48 h, 72 h and 120 h of infection in the infected animal. Based on these findings we suggest that P. alliacea up-regulates anti-bacterial immune response by enhancing both Th1 function and the activity of NK cells.

  2. Exacerbation of N-nitrosodiethylamine Induced Hepatotoxicity and DNA Damage in Mice Exposed to Chronic Unpredictable Stress

    Directory of Open Access Journals (Sweden)

    Nayeem Bilal

    2017-06-01

    Full Text Available Psychological stress contributes to increased susceptibility to a number of diseases including cancer. The present study was designed to assess the effect of chronic unpredictable stress on N-nitrosodiethylamine induced liver toxicity in terms of in vivo antioxidant status and DNA damage in Swiss albino mice. The animals used in this study were randomized into different groups based on the treatment with N-nitrosodiethylamine or chronic unpredictable stress alone and post-stress administration of N-nitrosodiethylamine. The mice were sacrificed after 12 weeks of treatment, and the status of major enzymatic and non-enzymatic antioxidants, liver function markers, lipid peroxidation and the extent of DNA damage were determined in circulation and liver tissues of all the groups. The N-nitrosodiethylamine treated group showed significantly compromised levels of the antioxidant enzymes, lipid peroxidation, and the liver function markers with enhanced DNA damage as compared to chronic unpredictable stress or control groups. A similar but less typical pattern observed in the chronic unpredictable stress treated mice. All the measured biochemical parameters were significantly altered in the group treated with the combination of chronic unpredictable stress and N-nitrosodiethylamine when compared to controls, or chronic unpredictable stress alone and/or N-nitrosodiethylamine alone treated groups. Thus, exposure to continuous, unpredictable stress conditions even in general life may significantly enhance the hepatotoxic potential of N-nitrosodiethylamine through an increase in the oxidative stress and DNA damage.

  3. Potential role of meflquine (antimalarial drug and methanol extract of Chenopodium ambrosioides and Sesbania sesban in mice infected with Schistosoma mansoni

    Directory of Open Access Journals (Sweden)

    Mohamed Abdel-Wahab El-Emam

    2015-08-01

    Full Text Available Objective: To elucidate the efficacy of mefloquine and methanol extract of the plants Chenopodium ambrosioides (C. ambrosioides and Sesbania sesban (S. sesban as a combined therapy for the treatment of Schistosoma mansoni (S. mansoni infected mice, and study the parasitological, biochemical and histological parameters of treated mice. Methods: Two groups of male Swiss Albino mice were infected with S. mansoni cercariae. The first group untreated served as control. The second group was orally treated with a single dose (200 mg/kg of mefloquine 3 weeks post infection, then subsequently divided into 2 subgroups; the first orally retreated with the plant extracts 1 000 mg/kg of S. sesban followed by 1 250 mg/kg of C. ambrosioides with an 1 h interval, for 2 successive days. The second sub-group was re-treated with the same (dose and method plant extracts after 7 weeks post infection. Results: The results showed that S. mansoni infected mice treated with mefloquine and the plants’ extracts 3 weeks post infection significantly (P < 0.01 reduced the worm burden/ mouse by 95.5% and the few worms recovered from sacrificed mice in this treatment failed to lay ova. Moreover, no worms were recovered from infected mice treated with mefloquine (3 weeks post infection and re-treated by the plant’s extracts at 7 weeks post infection. Also, treatment of infected mice with mefloquine followed by the plants’ extracts either at 3 or 7 weeks post infection ameliorated the activities of the serum enzymes alanine aminotransferase, aspartate aminotransferase, alkline phosphatase and acid phosphatase as well as the hepatic granulomatous lesions compared to infected untreated group. Conclusions: It is concluded that successive treatment of S. mansoni infected mice with mefloquine and methanol extract of the plants C. ambrosioides and S. sesban could be a promising device in the strategy of schistosomiasis control.

  4. A DESCRIPTIVE STUDY OF FUNGAL INFECTIONS IN CHRONICALLY DISCHARGING EARS

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    Sujatha

    2015-08-01

    Full Text Available BACKGROUND : Chronic Suppurative Otitis Media (CSOM is a disease of multiple aetiology and well known for its persis tence and recurrence inspite of treatment and are the bearbug of otologist, paediatrician and general practitioner. One of the reason s for the refractoriness to treatment and chronicity is coexist ing fungal infection of the ear. OBJECTIVES: Are to find out the prevalence of fungal infections in chronic discharging ears and to identify and isolate the type of fungus prevalent in these ears . MATERIALS AND METHOD S: Tertiary care hospital level descrip tive study was conducted in 50 cases of CSOM with actively discharging ears for a period of one year starting from February 2013. For all the cases aural swabs were collected from the diseased ear and were used for direct microscopic examination in potassi um hydroxide wet mount. Ear swab was cultured on Sabouraud’s dextrose agar plate for fungal cultures. The patient characteristics were prospectively recorded and results were analysed. CONCLUSION : There is high prevalence of coexisting fungal infection in actively discharging ears of CSOM patients

  5. Aged interleukin-10tm1Cgn chronically inflamed mice have substantially reduced fat mass, metabolic rate, and adipokines.

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    Reyhan M Westbrook

    Full Text Available Interleukin 10tm1Cgn (IL 10tm mice have been utilized as a model of chronic inflammation and declining health span because of their propensity to develop chronic activation in NFkB pathways, skeletal muscle and cardiac changes, and mitochondrial dysfunction. We hypothesized that older IL 10tm frail mice would have alterations similar to frail, older humans in measured parameters of glucose metabolism, oxygen consumption (VO2, respiratory quotient (RQ, spontaneous locomotor activity, body composition and plasma adipokine levels. To test this hypothesis, we investigated these metabolic parameters in cohorts of 3, 10, and 20 month old IL 10tm female mice and age and gender matched C57Bl/6 mice. Insulin sensitivity, glucose homeostasis, locomotor activity and RQ were not significantly altered between the two strains of mice. Interestingly, old IL 10tm mice had significantly decreased VO2 when normalized by lean mass, but not when normalized by fat mass or the lean/fat mass ratio. NMR based body composition analysis and dissection weights show that fat mass is decreased with age in IL 10tm mice compared to controls. Further, plasma adiponectin and leptin were also decreased in IL 10tm.These findings suggest that frailty observed in this mouse model of chronic inflammation may in part be driven by alterations in fat mass, hormone secretion and energy metabolism.

  6. IFNγ and IL-12 Restrict Th2 Responses during Helminth/Plasmodium Co-Infection and Promote IFNγ from Th2 Cells.

    Directory of Open Access Journals (Sweden)

    Stephanie M Coomes

    2015-07-01

    Full Text Available Parasitic helminths establish chronic infections in mammalian hosts. Helminth/Plasmodium co-infections occur frequently in endemic areas. However, it is unclear whether Plasmodium infections compromise anti-helminth immunity, contributing to the chronicity of infection. Immunity to Plasmodium or helminths requires divergent CD4+ T cell-driven responses, dominated by IFNγ or IL-4, respectively. Recent literature has indicated that Th cells, including Th2 cells, have phenotypic plasticity with the ability to produce non-lineage associated cytokines. Whether such plasticity occurs during co-infection is unclear. In this study, we observed reduced anti-helminth Th2 cell responses and compromised anti-helminth immunity during Heligmosomoides polygyrus and Plasmodium chabaudi co-infection. Using newly established triple cytokine reporter mice (Il4gfpIfngyfpIl17aFP635, we demonstrated that Il4gfp+ Th2 cells purified from in vitro cultures or isolated ex vivo from helminth-infected mice up-regulated IFNγ following adoptive transfer into Rag1-/- mice infected with P. chabaudi. Functionally, Th2 cells that up-regulated IFNγ were transcriptionally re-wired and protected recipient mice from high parasitemia. Mechanistically, TCR stimulation and responsiveness to IL-12 and IFNγ, but not type I IFN, was required for optimal IFNγ production by Th2 cells. Finally, blockade of IL-12 and IFNγ during co-infection partially preserved anti-helminth Th2 responses. In summary, this study demonstrates that Th2 cells retain substantial plasticity with the ability to produce IFNγ during Plasmodium infection. Consequently, co-infection with Plasmodium spp. may contribute to the chronicity of helminth infection by reducing anti-helminth Th2 cells and converting them into IFNγ-secreting cells.

  7. Zika Virus Infection in Mice Causes Panuveitis with Shedding of Virus in Tears

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    Jonathan J. Miner

    2016-09-01

    Full Text Available Zika virus (ZIKV is an emerging flavivirus that causes congenital abnormalities and Guillain-Barré syndrome. ZIKV infection also results in severe eye disease characterized by optic neuritis, chorioretinal atrophy, and blindness in newborns and conjunctivitis and uveitis in adults. We evaluated ZIKV infection of the eye by using recently developed mouse models of pathogenesis. ZIKV-inoculated mice developed conjunctivitis, panuveitis, and infection of the cornea, iris, optic nerve, and ganglion and bipolar cells in the retina. This phenotype was independent of the entry receptors Axl or Mertk, given that Axl−/−, Mertk−/−, and Axl−/−Mertk−/− double knockout mice sustained levels of infection similar to those of control animals. We also detected abundant viral RNA in tears, suggesting that virus might be secreted from lacrimal glands or shed from the cornea. This model provides a foundation for studying ZIKV-induced ocular disease, defining mechanisms of viral persistence, and developing therapeutic approaches for viral infections of the eye.

  8. Occult hepatitis B virus infection is not associated with disease progression of chronic hepatitis C virus infection.

    Science.gov (United States)

    Cho, Junhyeon; Lee, Sang Soo; Choi, Yun Suk; Jeon, Yejoo; Chung, Jung Wha; Baeg, Joo Yeong; Si, Won Keun; Jang, Eun Sun; Kim, Jin-Wook; Jeong, Sook-Hyang

    2016-11-14

    To clarify the prevalence of occult hepatitis B virus (HBV) infection (OBI) and the association between OBI and liver disease progression, defined as development of liver cirrhosis or hepatocellular carcinoma (HCC), worsening of Child-Pugh class, or mortality in cases of chronic hepatitis C virus (HCV) infection. This prospective cohort study enrolled 174 patients with chronic HCV infection (chronic hepatitis, n = 83; cirrhosis, n = 47; HCC, n = 44), and evaluated disease progression during a mean follow-up of 38.7 mo. OBI was defined as HBV DNA positivity in 2 or more different viral genomic regions by nested polymerase chain reaction using 4 sets of primers in the S, C, P and X open reading frame of the HBV genome. The overall OBI prevalence in chronic HCV patients at enrollment was 18.4%, with 16.9%, 25.5% and 13.6% in the chronic hepatitis C, liver cirrhosis and HCC groups, respectively ( P = 0.845). During follow-up, 52 patients showed disease progression, which was independently associated with aspartate aminotransferase > 40 IU/L, Child-Pugh score and sustained virologic response (SVR), but not with OBI positivity. In 136 patients who were not in the SVR state during the study period, OBI positivity was associated with neither disease progression, nor HCC development. The prevalence of OBI in chronic HCV patients was 18.4%, and OBI was not associated with disease progression in South Koreans.

  9. Swim stress reduces chronic pain in mice through an opioid mechanism.

    Science.gov (United States)

    Carmody, J; Cooper, K

    1987-03-09

    Chronic nociception has been studied in male mice by means of the formalin test in which forelimb motor behaviour is scored after subcutaneous formalin injection. The rating remained above 2.0 for 30 min after the injection (scale range 0-3). The magnitude of the nociception has been compared with that reported in other animal types. Mice are more sensitive than rats, cats and monkeys. The stress of a swim of 3 min has been found to reduce nociception by up to 25%. This analgesia is wholly opioid in nature, being abolished by a moderate dose of naloxone (1 mg/kg).

  10. Germinal center architecture disturbance during Plasmodium berghei ANKA infection in CBA mice

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    Pelajo-Machado Marcelo

    2007-05-01

    Full Text Available Abstract Background Immune responses to malaria blood stage infection are in general defective, with the need for long-term exposure to the parasite to achieve immunity, and with the development of immunopathology states such as cerebral malaria in many cases. One of the potential reasons for the difficulty in developing protective immunity is the poor development of memory responses. In this paper, the potential association of cellular reactivity in lymphoid organs (spleen, lymph nodes and Peyer's patches with immunity and pathology was evaluated during Plasmodium berghei ANKA infection in CBA mice. Methods CBA mice were infected with 1 × 106 P. berghei ANKA-parasitized erythrocytes and killed on days 3, 6–8 and 10 of infection. The spleen, lymph nodes and Peyer's patches were collected, fixed in Carson's formalin, cut in 5 μm sections, mounted in glass slides, stained with Lennert's Giemsa and haematoxylin-eosin and analysed with bright-field microscopy. Results Early (day 3 strong activation of T cells in secondary lymphoid organs was observed and, on days 6–8 of infection, there was overwhelming activation of B cells, with loss of conventional germinal center architecture, intense centroblast activation, proliferation and apoptosis but little differentiation to centrocytes. In the spleen, the marginal zone disappeared and the limits between the disorganized germinal center and the red pulp were blurred. Intense plasmacytogenesis was observed in the T cell zone. Conclusion The observed alterations, especially the germinal center architecture disturbance (GCAD with poor centrocyte differentiation, suggest that B cell responses during P. berghei ANKA infection in mice are defective, with potential impact on B cell memory responses.

  11. Apocynin and ebselen reduce influenza A virus-induced lung inflammation in cigarette smoke-exposed mice.

    Science.gov (United States)

    Oostwoud, L C; Gunasinghe, P; Seow, H J; Ye, J M; Selemidis, S; Bozinovski, S; Vlahos, R

    2016-02-15

    Influenza A virus (IAV) infections are a common cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Oxidative stress is increased in COPD, IAV-induced lung inflammation and AECOPD. Therefore, we investigated whether targeting oxidative stress with the Nox2 oxidase inhibitors and ROS scavengers, apocynin and ebselen could ameliorate lung inflammation in a mouse model of AECOPD. Male BALB/c mice were exposed to cigarette smoke (CS) generated from 9 cigarettes per day for 4 days. On day 5, mice were infected with 1 × 10(4.5) PFUs of the IAV Mem71 (H3N1). BALF inflammation, viral titers, superoxide production and whole lung cytokine, chemokine and protease mRNA expression were assessed 3 and 7 days post infection. IAV infection resulted in a greater increase in BALF inflammation in mice that had been exposed to CS compared to non-smoking mice. This increase in BALF inflammation in CS-exposed mice caused by IAV infection was associated with elevated gene expression of pro-inflammatory cytokines, chemokines and proteases, compared to CS alone mice. Apocynin and ebselen significantly reduced the exacerbated BALF inflammation and pro-inflammatory cytokine, chemokine and protease expression caused by IAV infection in CS mice. Targeting oxidative stress using apocynin and ebselen reduces IAV-induced lung inflammation in CS-exposed mice and may be therapeutically exploited to alleviate AECOPD.

  12. Effect of Morinda Morindiodes Extracts on Organs of Mice Infected ...

    African Journals Online (AJOL)

    Effect of Morinda Morindiodes Extracts on Organs of Mice Infected with ... The histological evaluation of the effect of Morinda(M.) morindiodes plant part(s) extracts in the treatment ... Control animals were given water for the same period of time.

  13. alpha-Glucosidase-albumin conjugates: effect of chronic administration in mice

    International Nuclear Information System (INIS)

    Allen, T.M.; Murray, L.; Bhardwaj, D.; Poznansky, M.J.

    1985-01-01

    Enzyme albumin conjugates have been proposed as a means of increasing the efficacy of enzyme use in vivo and decreasing immune response to the enzyme. Particulate drug carriers, however, have a pronounced tendency to localize in the mononuclear phagocyte (reticuloendothelial) system. The authors have examined in mice the effect on phagocytic index, tissue distribution and organ size of continued administration of conjugates of alpha-glucosidase with either homologous or heterologous albumin. Mice received 10 X 2-mg injections of bovine serum albumin (BSA) or mouse serum albumin (MSA), either free, polymerized or conjugated with alpha-glucosidase. Experiments involving BSA had to be terminated before the end of the experiment because of anaphylaxis, but these reactions were less severe to the polymerized albumin than to free albumin. Free BSA, BSA polymer and BSA-enzyme conjugates all caused a decrease in phagocytic index after six injections. Mice receiving MSA showed no evidence of anaphylaxis, but mice receiving six or more injections of free MSA, MSA polymer or MSA-enzyme conjugate had significantly decreased phagocytic indices as compared to controls. Phagocytic indices had returned to normal by 7 days after the final injection. Tissue distribution of 125 I-labeled albumin preparations was determined in either naive or chronically injected mice

  14. MicroRNA expression signatures in lungs of mice infected with Mycobacterium tuberculosis.

    Science.gov (United States)

    Malardo, Thiago; Gardinassi, Luiz Gustavo; Moreira, Bernardo Pereira; Padilha, Éverton; Lorenzi, Júlio César Cetrulo; Soares, Luana Silva; Gembre, Ana Flávia; Fontoura, Isabela Cardoso; de Almeida, Luciana Previato; de Miranda Santos, Isabel Kinney Ferreira; Silva, Célio Lopes; Coelho-Castelo, Arlete Aparecida Martins

    2016-12-01

    Tuberculosis (TB) is a major public health concern worldwide; however the factors that account for resistance or susceptibility to disease are not completely understood. Although some studies suggest that the differential expression of miRNAs in peripheral blood of TB patients could be useful as biomarkers of active disease, their involvement during the inflammatory process in lungs of infected individuals is unknown. Here, we evaluated the global expression of miRNAs in the lungs of mice experimentally infected with Mycobacterium tuberculosis on 30 and 60 days post-infection. We observed that several miRNAs were differentially expressed compared to uninfected mice. Furthermore, we verified that the expression of miR-135b, miR-21, miR-155, miR-146a, and miR-146b was significantly altered in distinct leukocyte subsets isolated from lungs of infected mice, while genes potentially targeted by those miRNAs were associated with a diversity of immune related molecular pathways. Importantly, we validated the inhibition of Pellino 1 expression by miR-135b in vitro. Overall, this study contributes to the understanding of the dynamics of miRNA expression in lungs during experimental TB and adds further perspectives into the role of miRNAs on the regulation of immune processes such as leukocyte activation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Helicobacter pylori gene silencing in vivo demonstrates urease is essential for chronic infection.

    Science.gov (United States)

    Debowski, Aleksandra W; Walton, Senta M; Chua, Eng-Guan; Tay, Alfred Chin-Yen; Liao, Tingting; Lamichhane, Binit; Himbeck, Robyn; Stubbs, Keith A; Marshall, Barry J; Fulurija, Alma; Benghezal, Mohammed

    2017-06-01

    Helicobacter pylori infection causes chronic active gastritis that after many years of infection can develop into peptic ulceration or gastric adenocarcinoma. The bacterium is highly adapted to surviving in the gastric environment and a key adaptation is the virulence factor urease. Although widely postulated, the requirement of urease expression for persistent infection has not been elucidated experimentally as conventional urease knockout mutants are incapable of colonization. To overcome this constraint, conditional H. pylori urease mutants were constructed by adapting the tetracycline inducible expression system that enabled changing the urease phenotype of the bacteria during established infection. Through tight regulation we demonstrate that urease expression is not only required for establishing initial colonization but also for maintaining chronic infection. Furthermore, successful isolation of tet-escape mutants from a late infection time point revealed the strong selective pressure on this gastric pathogen to continuously express urease in order to maintain chronic infection. In addition to mutations in the conditional gene expression system, escape mutants were found to harbor changes in other genes including the alternative RNA polymerase sigma factor, fliA, highlighting the genetic plasticity of H. pylori to adapt to a changing niche. The tet-system described here opens up opportunities to studying genes involved in the chronic stage of H. pylori infection to gain insight into bacterial mechanisms promoting immune escape and life-long infection. Furthermore, this genetic tool also allows for a new avenue of inquiry into understanding the importance of various virulence determinants in a changing biological environment when the bacterium is put under duress.

  16. Helicobacter pylori gene silencing in vivo demonstrates urease is essential for chronic infection.

    Directory of Open Access Journals (Sweden)

    Aleksandra W Debowski

    2017-06-01

    Full Text Available Helicobacter pylori infection causes chronic active gastritis that after many years of infection can develop into peptic ulceration or gastric adenocarcinoma. The bacterium is highly adapted to surviving in the gastric environment and a key adaptation is the virulence factor urease. Although widely postulated, the requirement of urease expression for persistent infection has not been elucidated experimentally as conventional urease knockout mutants are incapable of colonization. To overcome this constraint, conditional H. pylori urease mutants were constructed by adapting the tetracycline inducible expression system that enabled changing the urease phenotype of the bacteria during established infection. Through tight regulation we demonstrate that urease expression is not only required for establishing initial colonization but also for maintaining chronic infection. Furthermore, successful isolation of tet-escape mutants from a late infection time point revealed the strong selective pressure on this gastric pathogen to continuously express urease in order to maintain chronic infection. In addition to mutations in the conditional gene expression system, escape mutants were found to harbor changes in other genes including the alternative RNA polymerase sigma factor, fliA, highlighting the genetic plasticity of H. pylori to adapt to a changing niche. The tet-system described here opens up opportunities to studying genes involved in the chronic stage of H. pylori infection to gain insight into bacterial mechanisms promoting immune escape and life-long infection. Furthermore, this genetic tool also allows for a new avenue of inquiry into understanding the importance of various virulence determinants in a changing biological environment when the bacterium is put under duress.

  17. Concentration- and age-dependent effects of chronic caffeine on contextual fear conditioning in C57BL/6J mice

    Science.gov (United States)

    Poole, Rachel L.; Braak, David; Gould, Thomas J.

    2015-01-01

    Chronic caffeine exerts negligible effects on learning and memory in normal adults, but it is unknown whether this is also true for children and adolescents. The hippocampus, a brain region important for learning and memory, undergoes extensive structural and functional modifications during pre-adolescence and adolescence. As a result, chronic caffeine may have differential effects on hippocampus-dependent learning in pre-adolescents and adolescents compared with adults. Here, we characterized the effects of chronic caffeine and withdrawal from chronic caffeine on hippocampus-dependent (contextual) and hippocampus-independent (cued) fear conditioning in pre-adolescent, adolescent, and adult mice. The results indicate that chronic exposure to caffeine during pre-adolescence and adolescence enhances or impairs contextual conditioning depending on concentration, yet has no effect on cued conditioning. In contrast, withdrawal from chronic caffeine impairs contextual conditioning in pre-adolescent mice only. No changes in learning were seen for adult mice for either the chronic caffeine or withdrawal conditions. These findings support the hypothesis that chronic exposure to caffeine during pre-adolescence and adolescence can alter learning and memory and as changes were only seen in hippocampus-dependent learning, this suggests that the developing hippocampus may be sensitive to the effects of caffeine. PMID:25827925

  18. Concentration- and age-dependent effects of chronic caffeine on contextual fear conditioning in C57BL/6J mice.

    Science.gov (United States)

    Poole, Rachel L; Braak, David; Gould, Thomas J

    2016-02-01

    Chronic caffeine exerts negligible effects on learning and memory in normal adults, but it is unknown whether this is also true for children and adolescents. The hippocampus, a brain region important for learning and memory, undergoes extensive structural and functional modifications during pre-adolescence and adolescence. As a result, chronic caffeine may have differential effects on hippocampus-dependent learning in pre-adolescents and adolescents compared with adults. Here, we characterized the effects of chronic caffeine and withdrawal from chronic caffeine on hippocampus-dependent (contextual) and hippocampus-independent (cued) fear conditioning in pre-adolescent, adolescent, and adult mice. The results indicate that chronic exposure to caffeine during pre-adolescence and adolescence enhances or impairs contextual conditioning depending on concentration, yet has no effect on cued conditioning. In contrast, withdrawal from chronic caffeine impairs contextual conditioning in pre-adolescent mice only. No changes in learning were seen for adult mice for either the chronic caffeine or withdrawal conditions. These findings support the hypothesis that chronic exposure to caffeine during pre-adolescence and adolescence can alter learning and memory and as changes were only seen in hippocampus-dependent learning, which suggests that the developing hippocampus may be sensitive to the effects of caffeine. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. A Perfect Storm: Increased Colonization and Failure of Vaccination Leads to Severe Secondary Bacterial Infection in Influenza Virus-Infected Obese Mice

    Directory of Open Access Journals (Sweden)

    Erik A. Karlsson

    2017-09-01

    Full Text Available Obesity is a risk factor for developing severe disease following influenza virus infection; however, the comorbidity of obesity and secondary bacterial infection, a serious complication of influenza virus infections, is unknown. To fill this gap in knowledge, lean and obese C57BL/6 mice were infected with a nonlethal dose of influenza virus followed by a nonlethal dose of Streptococcus pneumoniae. Strikingly, not only did significantly enhanced death occur in obese coinfected mice compared to lean controls, but also high mortality was seen irrespective of influenza virus strain, bacterial strain, or timing of coinfection. This result was unexpected, given that most influenza virus strains, especially seasonal human A and B viruses, are nonlethal in this model. Both viral and bacterial titers were increased in the upper respiratory tract and lungs of obese animals as early as days 1 and 2 post-bacterial infection, leading to a significant decrease in lung function. This increased bacterial load correlated with extensive cellular damage and upregulation of platelet-activating factor receptor, a host receptor central to pneumococcal invasion. Importantly, while vaccination of obese mice against either influenza virus or pneumococcus failed to confer protection, antibiotic treatment was able to resolve secondary bacterial infection-associated mortality. Overall, secondary bacterial pneumonia could be a widespread, unaddressed public health problem in an increasingly obese population.

  20. Effect of the histaminergic antagonist over the pulmonary oedema growth in P. berghei - infected mice

    International Nuclear Information System (INIS)

    Martins, M.A.

    1985-01-01

    The involvement of histaminergic mechanisms in the pathogenesis of pulmonary oedema observed in p. berghei - infected mice was investigated. Histamine concentrations in plasma and whole blood of infected and normal mice were determined by radioenzymatic assay during the seven days of the infection. Elevated plasma and whole blood histamine levels were found at the last stages of infection (sixth day and seventh day) after intraperitoneal injection of parasitized erythrocytes, showing a close temporal correlation between the development of the oedema and the elevation of the circulating histamine concentrations. The participation of H 1 and H 2 receptors in the increase in vascular permeability (IVP) induced by histamine was also verified. (author)

  1. Acute or chronic life-threatening diseases associated with Epstein-Barr virus infection.

    Science.gov (United States)

    Okano, Motohiko; Gross, Thomas G

    2012-06-01

    Infectious mononucleosis (IM) is one of the representative, usually benign, acute diseases associated with primary Epstein-Barr virus (EBV) infection. IM is generally self-limiting and is characterized mostly by transient fever, lymphadenopathy and hepatosplenomegaly. However, very rarely primary EBV infection results in severe or fatal conditions such as hemophagocytic lymphohistiocytosis together with fulminant hepatitis designated as severe or fatal IM or EBV-associated hemophagocytic lymphohistiocytosis alone. In addition, chronic EBV-associated diseases include Burkitt's lymphoma, undifferentiated nasopharyngeal carcinoma, Hodgkin lymphoma, T-cell lymphoproliferative disorder (LPD)/lymphoma, natural killer-cell LPD including leukemia or lymphoma, gastric carcinoma, pyothorax-associated lymphoma and senile B-cell LPD as well as chronic active EBV infection and LPD/lymphoma in patients with immunodeficiency. The number of chronic life-threatening diseases linked to the EBV infection is increasingly reported and many of these diseases have a poor prognosis. This review will focus on the historical, pathogenetic, diagnostic, therapeutic and prophylactic issues of EBV-associated life-threatening diseases.

  2. Stressful Presentations: Mild Chronic Cold Stress in Mice Influences Baseline Properties of Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Kathleen Marie Kokolus

    2014-02-01

    Full Text Available The ability of dendritic cells to stimulate and regulate T cells is critical to effective anti-tumor immunity. Therefore, it is important to fully recognize any inherent factors which may influence DC function under experimental conditions, especially in laboratory mice since they are used so heavily to study immune responses. Physiological stress is well recognized to impair several arms of immune protection. The goals of this report are to briefly summarize previous work revealing how DCs respond to various forms of physiologically relevant stress and to present new data highlighting the potential for chronic mild cold stress inherent in mice housed at standard ambient temperatures required for laboratory mice to influence baseline DCs properties. Since recent data from our group shows that CD8+ T cell function is altered by mild chronic cold stress and since DC function is crucial for CD8+ T cell activation, we wondered whether mild cold stress may also be influencing DC properties. We found increased numbers of splenic DCs (CD11c+ in cold stressed mice compared to mice housed at a thermoneutral temperature, which significantly reduces cold stress. However, many of the DCs which are expanded in cold stressed mice express an immature phenotype. We also found that antigen presentation and ability of splenocytes to activate T cells were impaired compared to that seen in DCs isolated from mice at thermoneutrality. The new data presented here strongly suggest that the housing temperature of mice can affect fundamental properties of DC function which in turn could be influencing the response of DCs to added experimental stressors or other treatments.

  3. The role of bacterial biofilms in chronic infections

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas

    2013-01-01

    wounds, chronic otitis media and implant- and catheter-associated infections, affect millions of people in the developed world each year and many deaths occur as a consequence. In general, bacteria have two life forms during growth and proliferation. In one form, the bacteria exist as single, independent...... cells (planktonic) whereas in the other form, bacteria are organized into sessile aggregates. The latter form is commonly referred to as the biofilm growth phenotype. Acute infections are assumed to involve planktonic bacteria, which are generally treatable with antibiotics, although successful......Acute infections caused by pathogenic bacteria have been studied extensively for well over 100 years. These infections killed millions of people in previous centuries, but they have been combated effectively by the development of modern vaccines, antibiotics and infection control measures. Most...

  4. Immunohematopoietic modulation by oral β-1,3-glucan in mice infected with Listeria monocytogenes.

    Science.gov (United States)

    Torello, Cristiane O; de Souza Queiroz, Julia; Oliveira, Sueli C; Queiroz, Mary L S

    2010-12-01

    In this study we demonstrated that the oral administration of β-1,3-glucan (Imunoglucan®) protects mice from a lethal dose of Listeria monocytogenes (LM) when administered prophylactically for 10 days at the doses of 150 and 300 mg/kg, with survival rates up to 40%. These doses also prevented the myelosuppression and the splenomegaly caused by a sublethal infection with LM, due to increased numbers of granulocyte-macrophage progenitors (CFU-GM) in the bone marrow. Investigation of the production of colony-stimulating factors revealed an increased colony-stimulating activity (CSA) in the serum of infected mice pre-treated with Imunoglucan®. The treatment also restored the reduced ability of stromal cells to display myeloid progenitors in long-term bone marrow cultures (LTBMC) and up-regulated IL-6 and IL-1α production by these cells in the infected mice, which was consistent with higher number of non-adherent cells. Additional studies to investigate the levels of interferon-gamma (INF-γ) in the supernatant of splenocyte cultures demonstrated a further increase in the level of this cytokine in infected-treated mice, compared to infected controls. In all cases, no differences were observed between the responses of the two optimal biologically effective doses. In contrast, no significant changes were produced by the treatment with the 50mg/kg dose. In addition, no changes were observed in normal mice treated with the three doses used. All together our results suggest that orally given Imunoglucan® indirectly modulates immune activity and probably disengages Listeria induced suppression of these responses by inducing a higher reserve of myeloid progenitors in the bone marrow in consequence of biologically active cytokine release (CSFs, IL-1α, IL-6, and INF-γ). Copyright © 2010 Elsevier B.V. All rights reserved.

  5. Chronic Mycobacterium marinum Infection Acts as a Tumor Promoter in Japanese Medaka (Oryzias latipes)

    Science.gov (United States)

    An accumulating body of research indicates there is an increased cancer risk associated with chronic infections. The genus Mycobacterium contains a number of species, including M tuberculosis, which mount chronic infections and have been implicated in higher cancer risk. Several ...

  6. Altered social cognition in male BDNF heterozygous mice and following chronic methamphetamine exposure.

    Science.gov (United States)

    Manning, Elizabeth E; van den Buuse, Maarten

    2016-05-15

    Growing clinical evidence suggests that persistent psychosis which occurs in methamphetamine users is closely related to schizophrenia. However, preclinical studies in animal models have focussed on psychosis-related behaviours following methamphetamine, and less work has been done to assess endophenotypes relevant to other deficits observed in schizophrenia. Altered social behaviour is a feature of both the negative symptoms and cognitive deficits in schizophrenia, and significantly impacts patient functioning. We recently found that brain-derived neurotrophic factor (BDNF) heterozygous mice show disrupted sensitization to methamphetamine, supporting other work suggesting an important role of this neurotrophin in the pathophysiology of psychosis and the neuronal response to stimulant drugs. In the current study, we assessed social and cognitive behaviours in methamphetamine-treated BDNF heterozygous mice and wildtype littermate controls. Following chronic methamphetamine exposure male wildtype mice showed a 50% reduction in social novelty preference. Vehicle-treated male BDNF heterozygous mice showed a similar impairment in social novelty preference, with a trend for no further disruption by methamphetamine exposure. Female mice were unaffected in this task, and no groups showed any changes in sociability or short-term spatial memory. These findings suggest that chronic methamphetamine alters behaviour relevant to disruption of social cognition in schizophrenia, supporting other studies which demonstrate a close resemblance between persistent methamphetamine psychosis and schizophrenia. Together these findings suggest that dynamic regulation of BDNF signalling is necessary to mediate the effects of methamphetamine on behaviours relevant to schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Chronic exercise reduces hypothalamic transforming growth factor-β1 in middle-aged obese mice.

    Science.gov (United States)

    Silva, Vagner R R; Katashima, Carlos K; Lenhare, Luciene; Silva, Carla G B; Morari, Joseane; Camargo, Rafael L; Velloso, Licio A; Saad, Mario A; da Silva, Adelino S R; Pauli, Jose Rodrigo; Ropelle, Eduardo Rochete

    2017-08-28

    Obesity and aging are associated with hypothalamic inflammation, hyperphagia and abnormalities in the thermogenesis control. It has been demonstrated that the association between aging and obesity induces hypothalamic inflammation and metabolic disorders, at least in part, through the atypical hypothalamic transforming growth factor-β (TGF-β1). Physical exercise has been used to modulate several metabolic parameters. Thus, the aim of this study was to evaluate the impact of chronic exercise on TGF-β1 expression in the hypothalamus of Middle-Aged mice submitted to a one year of high-fat diet (HFD) treatment. We observed that long-term of HFD-feeding induced hypothalamic TGF-β1 accumulation, potentiated the hypothalamic inflammation, body weight gain and defective thermogenesis of Middle-Aged mice when compared to Middle-Aged animals fed on chow diet. As expected, chronic exercise induced negative energy balance, reduced food consumption and increasing the energy expenditure, which promotes body weight loss. Interestingly, exercise training reduced the TGF-β1 expression and IkB-α ser32 phosphorylation in the hypothalamus of Middle-Aged obese mice. Taken together our study demonstrated that chronic exercise suppressed the TGF-β1/IkB-α axis in the hypothalamus and improved the energy homeostasis in an animal model of obesity-associated to aging.

  8. Anatomopathological study in BALB/c mice brains experimentally infected with Toxoplasma gondii

    Directory of Open Access Journals (Sweden)

    Marcos Gontijo da Silva

    Full Text Available Toxoplasmosis is one of the most important diseases of the nervous central system, leading to severe symptoms and, many times, irreversible sequelae. This work demonstrated the main anatomopathological lesions caused by Toxoplasma gondii in brains from experimentally infected BALB/c mice. We analyzed 51 cases of mice that developed toxoplasmosis after experimental infection by intraperitoneal inoculation of blood, amniotic liquid and cerebrospinal fluid from fetuses, newly born children and pregnant women with clinical and laboratory signals of toxoplasmosis. In all experiments where we detected the parasite in mice we also detected pathological lesions in the animal brains with great polymorphism between experiments. Edema was the most found lesion in all cases. Besides, it was possible to demonstrate the inflammatory process in 82.4% of cases and necrosis in 64.7% of cases, in agreement with the literature that describes severe neurological damage in its hosts.

  9. Increased infectivity of anchorless mouse scrapie prions in transgenic mice overexpressing human prion protein.

    Science.gov (United States)

    Race, Brent; Phillips, Katie; Meade-White, Kimberly; Striebel, James; Chesebro, Bruce

    2015-06-01

    Prion protein (PrP) is found in all mammals, mostly as a glycoprotein anchored to the plasma membrane by a C-terminal glycosylphosphatidylinositol (GPI) linkage. Following prion infection, host protease-sensitive prion protein (PrPsen or PrPC) is converted into an abnormal, disease-associated, protease-resistant form (PrPres). Biochemical characteristics, such as the PrP amino acid sequence, and posttranslational modifications, such as glycosylation and GPI anchoring, can affect the transmissibility of prions as well as the biochemical properties of the PrPres generated. Previous in vivo studies on the effects of GPI anchoring on prion infectivity have not examined cross-species transmission. In this study, we tested the effect of lack of GPI anchoring on a species barrier model using mice expressing human PrP. In this model, anchorless 22L prions derived from tg44 mice were more infectious than 22L prions derived from C57BL/10 mice when tested in tg66 transgenic mice, which expressed wild-type anchored human PrP at 8- to 16-fold above normal. Thus, the lack of the GPI anchor on the PrPres from tg44 mice appeared to reduce the effect of the mouse-human PrP species barrier. In contrast, neither source of prions induced disease in tgRM transgenic mice, which expressed human PrP at 2- to 4-fold above normal. Prion protein (PrP) is found in all mammals, usually attached to cells by an anchor molecule called GPI. Following prion infection, PrP is converted into a disease-associated form (PrPres). While most prion diseases are species specific, this finding is not consistent, and species barriers differ in strength. The amino acid sequence of PrP varies among species, and this variability affects prion species barriers. However, other PrP modifications, including glycosylation and GPI anchoring, may also influence cross-species infectivity. We studied the effect of PrP GPI anchoring using a mouse-to-human species barrier model. Experiments showed that prions produced by

  10. Immunological aspects of Giardia muris and Spironucleus muris infections in inbred and outbred strains of laboratory mice: a comparative study.

    Science.gov (United States)

    Brett, S J; Cox, F E

    1982-08-01

    The intestinal flagellates, Giardia muris and Spironucleus muris, cause similar infections in CBA mice as determined by trophozoite and cyst counts. Both parasites occur all along the small intestine with G. muris, being mainly present in the anterior part and S. muris towards the posterior. The early stages of infection are similar in all strains of mice examined and peak levels of both trophozoites and cysts occur 1-2 weeks after infection. All strains of mice overcome the infection but the rate of recovery varies considerably between strains, being most rapid in BALB/c and slowest in A and C57BL.B10. Outbred mice are more variable in their recovery than inbred mice. After recovery, mice are partially resistant to reinfection with the homologous but not the heterologous parasite. Resistance to reinfection with S. muris is greatest in those strains that eliminate the primary infection most rapidly. Giardia muris and S. muris cause similar changes in the mucosa of the small intestine of BALB/c mice with increased intra-epithelial lymphocyte counts from 3 weeks onwards corresponding with the start of the elimination of the parasites from the gut. A reduction in villus height and increase in crypt depth is also characteristic of these infections.

  11. Management of Developmentally Disabled Children with Chronic Infections.

    Science.gov (United States)

    Andersen, Richard D.

    1988-01-01

    The nature of chronic infections in developmentally disabled children is reviewed, along with appropriate management strategies for care providers and implications for other children. Discussed are herpes simplex virus, cytomegalovirus, hepatitis B virus, and human immunodeficiency virus. (Author/JDD)

  12. Antileishmanial activity of licochalcone A in mice infected with Leishmania major and in hamsters infected with Leishmania donovani

    DEFF Research Database (Denmark)

    Chen, M; Christensen, S B; Theander, T G

    1994-01-01

    This study was designed to examine the antileishmanial activity of the oxygenated chalcone licochalcone A in mice and hamsters infected with Leishmania parasites. Intraperitoneal administration of licochalcone A at doses of 2.5 and 5 mg/kg of body weight per day completely prevented lesion...... development in BALB/c mice infected with Leishmania major. Treatment of hamsters infected with L. donovani with intraperitoneal administration of licochalcone A at a dose of 20 mg/kg of body weight per day for 6 consecutive days resulted in a > 96% reduction of parasite load in the liver and the spleen...... consecutive days resulted in > 65 and 85% reductions of L. donovani parasite loads in the liver and the spleen, respectively, compared with those of untreated control hamsters. These data clearly demonstrate that licochalcone A is a promising lead for the development of a new drug against leishmaniases....

  13. Ocimum basilicum improve chronic stress-induced neurodegenerative changes in mice hippocampus.

    Science.gov (United States)

    Ayuob, Nasra Naeim; El Wahab, Manal Galal Abd; Ali, Soad Shaker; Abdel-Tawab, Hanem Saad

    2018-01-22

    Alzheimer's disease (AD), one of the progressive neurodegenerative diseases might be associated with exposure to stress and altered living conditions. This study aimed to evaluate the effectiveness of Ocimum basilicum (OB) essential oils in improving the neurodegenerative-like changes induced in mice after exposed to chronic unpredictable mild stress (CUMS). Forty male Swiss albino mice divided into four groups (n = 10); the control, CUMS, CUMS + Fluoxetine, CUMS + OB were used. Behavioral tests, serum corticosterone level, hippocampus protein level of the glucocorticoid receptors (GRs) and brain-dreived neurotropic factor (BDNF) were determined after exposure to CUMS. Hippocampus was histopathologically examined. Data were analyzed using statistical package for the social sciences (SPSS) and P value of less than 0.05 was considered significant. OB diminished the depression manifestation as well as impaired short term memory observed in the mice after exposure to the CUMS as evidenced by the forced swimming and elevated plus maze test. OB also up-regulated the serum corticosterone level, hippocampal protein level of the glucocorticoid receptor and the brain-derived neurotropic factor and reduced the neurodegenerative and atrophic changes induced in the hippocampus after exposure to CUMS. Essential oils of OB alleviated the memory impairment and hippocampal neurodegenerative changes induced by exposure to the chronic unpredictable stress indicating that it is the time to test its effectiveness on patients suffering from Alzheimer disease.

  14. Response pattern's of immunoglobulins evaluation in different lineages of mice infected with T. cruzi

    International Nuclear Information System (INIS)

    Silva, Andreia dos Santos

    2006-01-01

    The present work has employed different mice lineages (A/J, C57BL/6, B6AF1, BXA1 and BXA2) that were challenged with different doses of T. cruzi. The objective was to evaluate the pattern of immunoglobulins response presented by resistant and susceptible mice to T. cruzi as well as the lineages developed from the matting between them. So that evaluation was done by using lineages serums' sample, analyzed by ELISA's method. In agreement with the results observed all the lineages presented higher response to IgG2a and IgG2b, if compared with the titles to IgG1. IgG1 immunoglobulins involve a type Th2 pattern response which expressed allergic immunological responses, while IgG2 involves a pattern response Th1 that expresses cellular immunological response. The different lineages used in this research also presented different immunological response pattern by the infection with T. cruzi. Mice of the lineage C57BL/6 are resistant to the infection, while the animals of the lineage A/J are susceptible. The animals of the lineage B6AF1 are more resistant to the infection than their original parental C57BL/6. The immunological response developed by hybrid mice present traces of both susceptible and resistant parental A/J and C57BL/6, respectively. The animals of the lineage BXA1 can be considered resistant to the infection, but they don't present the same control as that presented by those of the lineages B6AF1 and C57BL/6. The animals of the lineage BXA2 can be considered susceptible to the infection, but they can control it for a long period, surviving like this, longer than the animals of the lineage A/J. In addition it was observed that the IgG2b immunoglobulins are very important to the resistance of mice to T. cruzi infection. (author)

  15. Elevated carbon monoxide in the exhaled breath of mice during a systemic bacterial infection.

    Directory of Open Access Journals (Sweden)

    Alan G Barbour

    Full Text Available Blood is the specimen of choice for most laboratory tests for diagnosis and disease monitoring. Sampling exhaled breath is a noninvasive alternative to phlebotomy and has the potential for real-time monitoring at the bedside. Improved instrumentation has advanced breath analysis for several gaseous compounds from humans. However, application to small animal models of diseases and physiology has been limited. To extend breath analysis to mice, we crafted a means for collecting nose-only breath samples from groups and individual animals who were awake. Samples were subjected to gas chromatography and mass spectrometry procedures developed for highly sensitive analysis of trace volatile organic compounds (VOCs in the atmosphere. We evaluated the system with experimental systemic infections of severe combined immunodeficiency Mus musculus with the bacterium Borrelia hermsii. Infected mice developed bacterial densities of ∼10(7 per ml of blood by day 4 or 5 and in comparison to uninfected controls had hepatosplenomegaly and elevations of both inflammatory and anti-inflammatory cytokines. While 12 samples from individual infected mice on days 4 and 5 and 6 samples from uninfected mice did not significantly differ for 72 different VOCs, carbon monoxide (CO was elevated in samples from infected mice, with a mean (95% confidence limits effect size of 4.2 (2.8-5.6, when differences in CO2 in the breath were taken into account. Normalized CO values declined to the uninfected range after one day of treatment with the antibiotic ceftriaxone. Strongly correlated with CO in the breath were levels of heme oxygenase-1 protein in serum and HMOX1 transcripts in whole blood. These results (i provide further evidence of the informativeness of CO concentration in the exhaled breath during systemic infection and inflammation, and (ii encourage evaluation of this noninvasive analytic approach in other various other rodent models of infection and for utility in

  16. Protective effects of lactoferrin chimera and bovine lactoferrin in a mouse model of enterohaemorrhagic Escherichia coli O157:H7 infection

    NARCIS (Netherlands)

    Flores-Villaseñor, H.; Canizalez-Román, A.; Velazquez-Roman, J.; Nazmi, K.; Bolscher, J.G.M.; Leon-Sicairos, N.

    2012-01-01

    Mice orally infected with enterohaemorrhagic Escherichia coli (EHEC) O157:H7 were used to evaluate the activity of bovine lactoferrin (bLF) and the synthetic peptide LFchimera. Groups of BALB/c mice inoculated intragastrically with EHEC O157:H7 showed chronic intestinal infection with the pathogen

  17. Vitamin E reduces hepatic fibrosis in mice with Schistosoma japonicum infection.

    Science.gov (United States)

    Wang, Xuefeng; Zhang, Rongbo; Du, Jiuwei; Hu, Youying; Xu, Lifa; Lu, Jun; Ye, Song

    2012-02-01

    To investigate whether vitamin E protects against hepatic fibrosis in mice with Schistosoma japonicum infection, 24 pathogen-free Kunming mice were selected and randomly divided into four groups: control (uninfected, untreated), model (infected, untreated), low-dose intervention (infected, vitamin E-treated, 30 mg/g bodyweight/day) and high-dose intervention (infected, vitamin E-treated, 60 mg/g bodyweight/day). Mice were infected with Schistosoma japonicum by inoculating abdominal skin with snail hosts. The activities of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were detected in hepatic tissue by colorimetry. The expression levels of laminin (LN), hyaluronic acid (HA), procollagen type Ⅲ (PC-III) and type Ⅳ collagen (IV-C) were detected in the serum by radioimmunoassay. Finally, areas and numbers of granulomas were assessed through histopathology 42 days following treatment. The results revealed that mean areas of granulomas were smaller in the low- and high-dose intervention groups compared to those in the model group. Furthermore, the higher dose of vitamin E resulted in smaller granulomas than the low dose. The levels of LN, HA, PC-III and IV-C in the serum were lower following vitamin E treatment than in the model group. By contrast, activity of SOD, GPx and CAT in hepatic tissue was higher following vitamin E treatment compared to the model group. The activity of MDA was lower in hepatic tissue following vitamin E treatment compared to the model group, but was higher compared to controls. In general, the higher dose of vitamin E affected measurements to a greater extent than the lower dose. In conclusion, vitamin E treatment may reduce the growth of granulomas, slowing the process of hepatic fibrosis, and this effect may be the result of the altered activity of the oxidation-reduction enzyme system.

  18. Role of the chemokine receptors CCR1, CCR2 and CCR4 in the pathogenesis of experimental dengue infection in mice.

    Directory of Open Access Journals (Sweden)

    Rodrigo Guabiraba

    Full Text Available Dengue virus (DENV, a mosquito-borne flavivirus, is a public health problem in many tropical countries. Recent clinical data have shown an association between levels of different chemokines in plasma and severity of dengue. We evaluated the role of CC chemokine receptors CCR1, CCR2 and CCR4 in an experimental model of DENV-2 infection in mice. Infection of mice induced evident clinical disease and tissue damage, including thrombocytopenia, hemoconcentration, lymphopenia, increased levels of transaminases and pro-inflammatory cytokines, and lethality in WT mice. Importantly, infected WT mice presented increased levels of chemokines CCL2/JE, CCL3/MIP-1α and CCL5/RANTES in spleen and liver. CCR1⁻/⁻ mice had a mild phenotype with disease presentation and lethality similar to those of WT mice. In CCR2⁻/⁻ mice, lethality, liver damage, levels of IL-6 and IFN-γ, and leukocyte activation were attenuated. However, thrombocytopenia, hemoconcentration and systemic TNF-α levels were similar to infected WT mice. Infection enhanced levels of CCL17/TARC, a CCR4 ligand. In CCR4⁻/⁻ mice, lethality, tissue injury and systemic inflammation were markedly decreased. Despite differences in disease presentation in CCR-deficient mice, there was no significant difference in viral load. In conclusion, activation of chemokine receptors has discrete roles in the pathogenesis of dengue infection. These studies suggest that the chemokine storm that follows severe primary dengue infection associates mostly to development of disease rather than protection.

  19. Active invasion of oral and aortic tissues by Porphyromonas gingivalis in mice causally links periodontitis and atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Irina M Velsko

    Full Text Available Atherosclerotic vascular disease is a leading cause of myocardial infarction and cerebrovascular accident, and independent associations with periodontal disease (PD are reported. PD is caused by polymicrobial infections and aggressive immune responses. Genomic DNA of Porphyromonas gingivalis, the best-studied bacterial pathogen associated with severe PD, is detected within atherosclerotic plaque. We examined causal relationships between chronic P. gingivalis oral infection, PD, and atherosclerosis in hyperlipidemic ApoEnull mice. ApoEnull mice (n = 24 were orally infected with P. gingivalis for 12 and 24 weeks. PD was assessed by standard clinical measurements while the aorta was examined for atherosclerotic lesions and inflammatory markers by array. Systemic inflammatory markers serum amyloid A, nitric oxide, and oxidized low-density lipoprotein were analyzed. P. gingivalis infection elicited specific antibodies and alveolar bone loss. Fluorescent in situ hybridization detected viable P. gingivalis within oral epithelium and aorta, and genomic DNA was detected within systemic organs. Aortic plaque area was significantly increased in P. gingivalis-infected mice at 24 weeks (P<0.01. Aortic RNA and protein arrays indicated a strong Th2 response. Chronic oral infection with P. gingivalis results in a specific immune response, significant increases in oral bone resorption, aortic inflammation, viable bacteria in oral epithelium and aorta, and plaque development.

  20. A long-term intake of a protein hydrolysate seems to increase the risk of encephalopathy in mice infected with Schistosoma mansoni

    Directory of Open Access Journals (Sweden)

    Haroldo S Ferreira

    1998-01-01

    Full Text Available Previous investigations showed that Schistosoma mansoni infection aggravates protein malabsorption in undernourished mice and this can be reverted by administration of casein hydrolysate. The present study was undertaken to evaluate the effects of ingestion of casein hydrolysate for long periods. Albino Swiss mice were divided into eight groups. Diets contained 5% (undernourished or 20% (controls casein levels. For each group there were sub-groups ingesting whole or hydrolysed casein for 12 weeks. Infection with S. mansoni developed in half of the animals under each diet. All undernourished mice developed malabsorption. Low albuminemia was detected in infected animals independently of the protein level in the diet. However, albuminemia was lower in infected controls than in undernourished non-infected mice, suggesting a deficient liver protein synthesis. Infected mice fed on a 20% protein hydrolysed diet exhibited low weight gain and high mortality rates. On the other hand, non-infected mice ingesting the same diet had the highest body weights. We are investigating the hypothesis that infected mice, even when fed normal diets, are unable to metabolise large amounts of amino acids due to the liver lesions related to schistosomiasis and as a result die of hepatic coma. In some of them, the excessive accumulation of ammonia in the blood enhances the outcome of an encephalopathy.

  1. Chronic Intermittent Hypoxia Induces Chronic Low-Grade Neuroinflammation in the Dorsal Hippocampus of Mice.

    Science.gov (United States)

    Sapin, Emilie; Peyron, Christelle; Roche, Frédéric; Gay, Nadine; Carcenac, Carole; Savasta, Marc; Levy, Patrick; Dematteis, Maurice

    2015-10-01

    Obstructive sleep apnea (OSA) induces cognitive impairment that involves intermittent hypoxia (IH). Because OSA is recognized as a low-grade systemic inflammatory disease and only some patients develop cognitive deficits, we investigated whether IH-related brain consequences shared similar pathophysiology and required additional factors such as systemic inflammation to develop. Nine-week-old male C57BL/6J mice were exposed to 1 day, 6 or 24 w of IH (alternating 21-5% FiO2 every 30 sec, 8 h/day) or normoxia. Microglial changes were assessed in the functionally distinct dorsal (dH) and ventral (vH) regions of the hippocampus using Iba1 immunolabeling. Then the study concerned dH, as vH only tended to be lately affected. Seven proinflammatory and anti-inflammatory cytokine messenger RNA (mRNA) were assessed at all time points using semiquantitative real-time reverse transcription polymerase chain reaction (RT-PCR). Similar mRNA analysis was performed after 6 w IH or normoxia associated for the past 3 w with repeated intraperitoneal low-dose lipopolysaccharide or saline. Chronic (6, 24 w) but not acute IH induced significant microglial changes in dH only, including increased density and morphological features of microglia priming. In dH, acute but not chronic IH increased IL-1β and RANTES/CCL5 mRNA, whereas the other cytokines remained unchanged. In contrast, chronic IH plus lipopolysaccharide increased interleukin (IL)-6 and IL10 mRNA whereas lipopolysaccharide alone did not affect these cytokines. The obstructive sleep apnea component intermittent hypoxia (IH) causes low-grade neuroinflammation in the dorsal hippocampus of mice, including early but transient cytokine elevations, delayed but long-term microglial changes, and cytokine response alterations to lipopolysaccharide inflammatory challenge. These changes may contribute to IH-induced cognitive impairment and pathological brain aging. © 2015 Associated Professional Sleep Societies, LLC.

  2. Turnover of T cells in murine gammaherpesvirus 68-infected mice

    DEFF Research Database (Denmark)

    Hamilton-Easton, A M; Christensen, Jan Pravsgaard; Doherty, P C

    1999-01-01

    Respiratory challenge of C57BL/6 mice with murine gammaherpesvirus 68 induces proliferation of T lymphocytes early after infection, as evidenced by incorporation of the DNA precursor bromodeoxyuridine. Using pulse-chase analysis, splenic and peripheral blood activated T lymphocytes were found...

  3. Therapeutic Efficacy of Vectored PGT121 Gene Delivery in HIV-1-Infected Humanized Mice.

    Science.gov (United States)

    Badamchi-Zadeh, Alexander; Tartaglia, Lawrence J; Abbink, Peter; Bricault, Christine A; Liu, Po-Ting; Boyd, Michael; Kirilova, Marinela; Mercado, Noe B; Nanayakkara, Ovini S; Vrbanac, Vladimir D; Tager, Andrew M; Larocca, Rafael A; Seaman, Michael S; Barouch, Dan H

    2018-04-01

    Broadly neutralizing antibodies (bNAbs) are being explored for HIV-1 prevention and cure strategies. However, administration of purified bNAbs poses challenges in resource-poor settings, where the HIV-1 disease burden is greatest. In vivo vector-based production of bNAbs represents an alternative strategy. We investigated adenovirus serotype 5 (Ad5) and adeno-associated virus serotype 1 (AAV1) vectors to deliver the HIV-1-specific bNAb PGT121 in wild-type and immunocompromised C57BL/6 mice as well as in HIV-1-infected bone marrow-liver-thymus (BLT) humanized mice. Ad5.PGT121 and AAV1.PGT121 produced functional antibody in vivo Ad5.PGT121 produced PGT121 rapidly within 6 h, whereas AAV1.PGT121 produced detectable PGT121 in serum by 72 h. Serum PGT121 levels were rapidly reduced by the generation of anti-PGT121 antibodies in immunocompetent mice but were durably maintained in immunocompromised mice. In HIV-1-infected BLT humanized mice, Ad5.PGT121 resulted in a greater reduction of viral loads than did AAV1.PGT121. Ad5.PGT121 also led to more-sustained virologic control than purified PGT121 IgG. Ad5.PGT121 afforded more rapid, robust, and durable antiviral efficacy than AAV1.PGT121 and purified PGT121 IgG in HIV-1-infected humanized mice. Further evaluation of vector delivery of HIV-1 bNAbs is warranted, although approaches to prevent the generation of antiantibody responses may also be required. IMPORTANCE Broadly neutralizing antibodies (bNAbs) are being explored for HIV-1 prevention and cure strategies, but delivery of purified antibodies may prove challenging. We investigated adenovirus serotype 5 (Ad5) and adeno-associated virus serotype 1 (AAV1) vectors to deliver the HIV-1-specific bNAb PGT121. Ad5.PGT121 afforded more rapid, robust, and durable antiviral efficacy than AAV1.PGT121 and purified PGT121 IgG in HIV-1-infected humanized mice. Copyright © 2018 Badamchi-Zadeh et al.

  4. Chronic pulmonary infection with Stenotrophomonas maltophilia and lung function in patients with cystic fibrosis

    DEFF Research Database (Denmark)

    Dalbøge, C S; Hansen, C R; Pressler, T

    2011-01-01

    Background The clinical consequences of chronic Stenotrophomonas maltophilia infection in cystic fibrosis (CF) patient are still unclear. Method All patients treated in the Copenhagen CF centre (N=278) from 1 January 2008 to 31 December 2009 were included. Each patient chronically infected with S...

  5. IL-21 augments NK effector functions in chronically HIV-infected individuals

    Science.gov (United States)

    Strbo, Natasa; de Armas, Lesley; Liu, Huanliang; Kolber, Michael A.; Lichtenheld, Mathias; Pahwa, Savita

    2009-01-01

    Objective This study addresses the interleukin (IL)-21 effects on resting peripheral blood NK cells in chronically HIV-infected individuals. Design The effects of IL-21 on perforin expression, proliferation, degranulation, IFN-γ production, cytotoxicity and induction of STAT phosphorylation in NK cells were determined in vitro. Methods Peripheral blood mononuclear cells from HIV-infected and healthy individuals were incubated in vitro for 6h, 24h or 5 days with IL-21 or IL-15. Percentages of perforin, IFN-γ, CD107a, NKG2D and STAT3-5 positive cells were determined within NK cell populations. K562 cells were used as target cells in NK cytotoxicity assay. Results Frequency of CD56dim cells in chronically HIV-infected individuals was diminished. Perforin expression in CD56dim and CD56bright was comparable in healthy and HIV-infected individuals. IL-15 up-regulated perforin expression primarily in CD56bright NK cells while IL-21 up-regulated perforin in both NK subsets. IL-21 and IL- 15 up-regulated CD107a and IFN-γ as well as NK cytotoxicity. IL-15 predominantly activated STAT5, while IL-21 activated STAT5 and STAT3. IL-15, but not IL-21 increased NK cell proliferation in uninfected and HIV-infected individuals. Conclusion IL-21 augments NK effector functions in chronically HIV-infected individuals and due to its perforin enhancing properties it has potential for immunotherapy or as a vaccine adjuvant. PMID:18670213

  6. Tissue-specific down-regulation of RIPK 2 in Mycobacterium leprae-infected nu/nu mice

    Directory of Open Access Journals (Sweden)

    Gue-Tae Chae

    1992-01-01

    Full Text Available RIPK 2 is adapter molecule in the signal pathway involved in Toll-like receptors. However, there has been no reported association between receptor-interacting serine/threonine kinase 2 (RIPK 2 expression and the infectious diseases involving mycobacterial infection. This study found that its expression was down-regulated in the footpads and skin but was up-regulated in the liver of Mycobacterium leprae-infected nu/nu mice compared with those of the M. leprae non-infected nu/nu mice. It was observed that the interlukin-12p40 and interferon-γ genes involved in the susceptibility of M. leprae were down-regulated in the skin but were up-regulated in the liver. Overall, this suggests that regulation of RIPK 2 expression is tissue-specifically associated with M. leprae infection.

  7. Chronic traumatic stress impairs memory in mice: Potential roles of acetylcholine, neuroinflammation and corticotropin releasing factor expression in the hippocampus.

    Science.gov (United States)

    Bhakta, Ami; Gavini, Kartheek; Yang, Euitaek; Lyman-Henley, Lani; Parameshwaran, Kodeeswaran

    2017-09-29

    Chronic stress in humans can result in multiple adverse psychiatric and neurobiological outcomes, including memory deficits. These adverse outcomes can be more severe if each episode of stress is very traumatic. When compared to acute or short term stress relatively little is known about the effects of chronic traumatic stress on memory and molecular changes in hippocampus, a brain area involved in memory processing. Here we studied the effects of chronic traumatic stress in mice by exposing them to adult Long Evan rats for 28 consecutive days and subsequently analyzing behavioral outcomes and the changes in the hippocampus. Results show that stressed mice developed memory deficits when assayed with radial arm maze tasks. However, chronic traumatic stress did not induce anxiety, locomotor hyperactivity or anhedonia. In the hippocampus of stressed mice interleukin-1β protein expression was increased along with decreased corticotropin releasing hormone (CRH) gene expression. Furthermore, there was a reduction in acetylcholine levels in the hippocampus of stressed mice. There were no changes in brain derived neurotrophic factor (BDNF) or nerve growth factor (NGF) levels in the hippocampus of stressed mice. Gene expression of immediate early genes (Zif268, Arc, C-Fos) as well as glucocorticoid and mineralocorticoid receptors were also not affected by chronic stress. These data demonstrate that chronic traumatic stress followed by a recovery period might lead to development of resilience resulting in the development of selected, most vulnerable behavioral alterations and molecular changes in the hippocampus. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. HAART impact on prevalence of chronic otitis media in Brazilian HIV-infected children.

    Science.gov (United States)

    Weber, Raimar; Pinheiro Neto, Carlos Diógenes; Miziara, Ivan Dieb; Araújo Filho, Bernardo Cunha

    2006-01-01

    The advent of new antiretroviral drugs such as protease inhibitors has generated sensible changes in morbity and mortality in HIV-infected patients. To evaluate the impact of Highly Active Antiretroviral Therapy (HAART) on the prevalence of chronic otitis media in HIV-infected pediatric population. We analyzed medical charts of 471 children aged zero to 12 years and 11 months with HIV infection from an Ambulatory of ENT and AIDS. Children were divided according to the age: 0 to 5 years and 11 months and 6 to 12 years and 11 months and classified as having chronic otitis media based on history, physical examination, audiologic and tympanometric data. Prevalence of chronic otitis media, as well as CD4+ lymphocyte count were compared between groups in use of HAART and the group without HAART. Out of 459 children, 65 (14.2%) had chronic otitis media. We observed that in children aged 0 to 5 years and 11 months who were taking HAART there was significant lower prevalence of chronic otitis media (p=0.02). The use of HAART was associated to higher mean CD4+ lymphocyte count (pmedia in HIV infected children, probably due to increase in mean CD4+ lymphocyte count.

  9. Exacerbation of autoimmune neuro-inflammation in mice cured from blood-stage Plasmodium berghei infection.

    Directory of Open Access Journals (Sweden)

    Rodolfo Thomé

    Full Text Available The thymus plays an important role shaping the T cell repertoire in the periphery, partly, through the elimination of inflammatory auto-reactive cells. It has been shown that, during Plasmodium berghei infection, the thymus is rendered atrophic by the premature egress of CD4+CD8+ double-positive (DP T cells to the periphery. To investigate whether autoimmune diseases are affected after Plasmodium berghei NK65 infection, we immunized C57BL/6 mice, which was previously infected with P. berghei NK65 and treated with chloroquine (CQ, with MOG35-55 peptide and the clinical course of Experimental Autoimmune Encephalomyelitis (EAE was evaluated. Our results showed that NK65+CQ+EAE mice developed a more severe disease than control EAE mice. The same pattern of disease severity was observed in MOG35-55-immunized mice after adoptive transfer of P. berghei-elicited splenic DP-T cells. The higher frequency of IL-17+- and IFN-γ+-producing DP lymphocytes in the Central Nervous System of these mice suggests that immature lymphocytes contribute to disease worsening. To our knowledge, this is the first study to integrate the possible relationship between malaria and multiple sclerosis through the contribution of the thymus. Notwithstanding, further studies must be conducted to assert the relevance of malaria-induced thymic atrophy in the susceptibility and clinical course of other inflammatory autoimmune diseases.

  10. Effectiveness of wet-cupping in treatment of BALB/c mice infected by ...

    African Journals Online (AJOL)

    Alireza Ahmadi, MD, PhD

    Then all mice were killed and their spleen and lymph node cells were cultured and the level of IFN- γ and IL-4 of cultured cells supernatant were measured ... The protozoan L. major is an obligate intracellular parasite, which can infect various mammalian hosts such as rodents, dogs, and humans. Infection in humans with ...

  11. Serum sphingomyelin has potential to reflect hepatic injury in chronic hepatitis B virus infection

    OpenAIRE

    Su-Jun Zheng; Feng Qu; Jun-Feng Li; Jing Zhao; Jing-Yun Zhang; Mei Liu; Feng Ren; Yu Chen; Jin-Lan Zhang; Zhong-Ping Duan

    2015-01-01

    Objective: To explore the relation between serum sphingolipids and hepatic injury in chronic HBV infection. Methods: A cohort of participants including 48 healthy persons, 103 chronic HBV-infected patients containing chronic hepatitis B (CHB) and HBV-related cirrhosis were included. High performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) was performed to detect serum sphingolipids. The serological indicators were detected and quantified. The valid liver biop...

  12. An efficient chronic unpredictable stress protocol to induce stress-related responses in C57BL/6 mice

    Directory of Open Access Journals (Sweden)

    Susana eMonteiro

    2015-02-01

    Full Text Available Exposure to chronic stress can have broad effects on health ranging from increased predisposition for neuropsychiatric disorders to deregulation of immune responses. The chronic unpredictable stress (CUS protocol has been widely used to study the impact of stress exposure in several animal models and consists in the random, intermittent and unpredictable exposure to a variety of stressors during several weeks. CUS has consistently been shown to induce behavioral and immunological alterations typical of the chronic stress response. Unfortunately C57BL/6 mice, one of the most widely used mouse strains, due to the great variety of genetically modified lines, seem to be resistant to the commonly used 4-week-long CUS protocol. The definition of an alternative CUS protocol allowing the use of C57BL/6 mice in chronic stress experiments is a need. Here we show that by extending the CUS protocol to 8 weeks is possible to induce a chronic stress response in C57BL/6 mice, as revealed by abrogated body weight gain, increased adrenals weight and an overactive hypothalamic-pituitary-adrenal (HPA axis with increased levels of serum corticosterone. Moreover, we also observed stress-associated behavioral alterations, including the potentiation of anxious-like and depressive-like behaviors and a reduction of exploratory behavior, as well as subtle stress-related changes in the cell population of the thymus and of the spleen.The present protocol for C57BL/6 mice consistently triggers the spectrum of CUS-induced changes observed in rats and, thus, will be highly useful to researchers that need to use this particular mouse strain as an animal model of neuropsychiatric disorders and/or immune deregulation related to chronic unpredictable stress.

  13. Effects of gamma radiation and azathioprine on Brucella abortus infection in BALB/c mice

    Energy Technology Data Exchange (ETDEWEB)

    Elzer, P.H.; Rowe, G.E.; Enright, F.M.; Winter, A.J. (Department of Veterinary Microbiology, Immunology and Parasitology, College of Veterinary Medicine, Cornell University, Ithaca, NY (United States))

    1991-06-01

    Sublethal irradiation of BALB/c mice 4 hours prior to inoculation with 5 {times} 10(4) virulent Brucella abortus, caused significant (P less than 0.01) reductions in bacterial numbers in comparison with numbers in unirradiated controls. Numbers of brucellae in the spleen were significantly lower by 5 days after inoculation and decreased thereafter, so that at 2 and 3 weeks after inoculation, there were up to 1,000-fold fewer organisms in the spleen of irradiated mice. The number of brucellae in the spleen increased in irradiated mice thereafter. The course of events in the liver was similar, but developed more slowly, and peak differences in bacterial numbers were about 1 log less. These phenomena were not attributable to differences in implantation of brucellae in the liver or spleen, nor to an abnormal distribution of organisms in other organs of irradiated mice. Irradiation of mice during the plateau phase of infection also resulted in significant (P less than 0.05) reductions in bacterial counts in the spleen during the succeeding 4 weeks. Macrophage activation in the spleen, measured by a Listeria monocytogenes-killing assay, was significantly (P less than 0.01) increased by irradiation alone at 1 week after inoculation and at that time was significantly (P less than 0.01) greater in B abortus-infected, irradiated mice than in B abortus-infected controls. Histologic, cytologic, and immunologic studies revealed that the decrease in numbers of organisms between 1 and 2 weeks after inoculation in irradiated mice occurred at a time when their immune response to B abortus was suppressed and when numbers of neutrophils and monocytes infiltrating the spleen were significantly (P less than 0.01) diminished.

  14. Effects of gamma radiation and azathioprine on Brucella abortus infection in BALB/c mice

    International Nuclear Information System (INIS)

    Elzer, P.H.; Rowe, G.E.; Enright, F.M.; Winter, A.J.

    1991-01-01

    Sublethal irradiation of BALB/c mice 4 hours prior to inoculation with 5 x 10(4) virulent Brucella abortus, caused significant (P less than 0.01) reductions in bacterial numbers in comparison with numbers in unirradiated controls. Numbers of brucellae in the spleen were significantly lower by 5 days after inoculation and decreased thereafter, so that at 2 and 3 weeks after inoculation, there were up to 1,000-fold fewer organisms in the spleen of irradiated mice. The number of brucellae in the spleen increased in irradiated mice thereafter. The course of events in the liver was similar, but developed more slowly, and peak differences in bacterial numbers were about 1 log less. These phenomena were not attributable to differences in implantation of brucellae in the liver or spleen, nor to an abnormal distribution of organisms in other organs of irradiated mice. Irradiation of mice during the plateau phase of infection also resulted in significant (P less than 0.05) reductions in bacterial counts in the spleen during the succeeding 4 weeks. Macrophage activation in the spleen, measured by a Listeria monocytogenes-killing assay, was significantly (P less than 0.01) increased by irradiation alone at 1 week after inoculation and at that time was significantly (P less than 0.01) greater in B abortus-infected, irradiated mice than in B abortus-infected controls. Histologic, cytologic, and immunologic studies revealed that the decrease in numbers of organisms between 1 and 2 weeks after inoculation in irradiated mice occurred at a time when their immune response to B abortus was suppressed and when numbers of neutrophils and monocytes infiltrating the spleen were significantly (P less than 0.01) diminished

  15. Chronic hepatitis C infection is associated with insulin resistance and lipid profiles.

    Science.gov (United States)

    Dai, Chia-Yen; Yeh, Ming-Lun; Huang, Chung-Feng; Hou, Chen-Hsiu; Hsieh, Ming-Yen; Huang, Jee-Fu; Lin, I-Ling; Lin, Zu-Yau; Chen, Shinn-Chern; Wang, Liang-Yen; Chuang, Wan-Long; Yu, Ming-Lung; Tung, Hung-Da

    2015-05-01

    Chronic hepatitis C virus (HCV) infection has been suggested to be associated with non-insulin-dependent diabetes mellitus and lipid profiles. This study aimed to investigate the possible relationships of insulin resistance (IR) and lipid profiles with chronic hepatitis C (CHC) patients in Taiwan. We enrolled 160 hospital-based CHC patients with liver biopsy and the 480 controlled individuals without CHC and chronic hepatitis B from communities without known history of non-insulin-dependent diabetes mellitus. Fasting plasma glucose, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), alanine aminotransferase, and serum insulin levels, and homeostasis model assessment (HOMA-IR) were tested. When comparing factors between CHC patients, and sex- and age-matched controls who had no HCV infection, patients with HCV infection had a significantly higher alanine aminotransferase level, fasting plasma glucose level, insulin level, and HOMA-IR (P C and LDL-C levels (all P  2.5]), a high body mass index, TGs, and HCV RNA level are independent factors significantly associated with high HOMA-IR in multivariate logistic analyses. Chronic HCV infection was associated with metabolic characteristics including IR and lipid profile. IR was also associated with virological characteristics. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  16. Virus-neutralizing antibody response of mice to consecutive infection with human and avian influenza A viruses.

    Science.gov (United States)

    Janulíková, J; Stropkovská, A; Bobišová, Z; Košík, I; Mucha, V; Kostolanský, F; Varečková, E

    2015-06-01

    In this work we simulated in a mouse model a naturally occurring situation of humans, who overcame an infection with epidemic strains of influenza A, and were subsequently exposed to avian influenza A viruses (IAV). The antibody response to avian IAV in mice previously infected with human IAV was analyzed. We used two avian IAV (A/Duck/Czechoslovakia/1956 (H4N6) and the attenuated virus rA/Viet Nam/1203-2004 (H5N1)) as well as two human IAV isolates (virus A/Mississippi/1/1985 (H3N2) of medium virulence and A/Puerto Rico/8/1934 (H1N1) of high virulence). Two repeated doses of IAV of H4 or of H5 virus elicited virus-specific neutralizing antibodies in mice. Exposure of animals previously infected with human IAV (of H3 or H1 subtype) to IAV of H4 subtype led to the production of antibodies neutralizing H4 virus in a level comparable with the level of antibodies against the human IAV used for primary infection. In contrast, no measurable levels of virus-neutralizing (VN) antibodies specific to H5 virus were detected in mice infected with H5 virus following a previous infection with human IAV. In both cases the secondary infection with avian IAV led to a significant increase of the titer of VN antibodies specific to the corresponding human virus used for primary infection. Moreover, cross-reactive HA2-specific antibodies were also induced by sequential infection. By virtue of these results we suggest that the differences in the ability of avian IAV to induce specific antibodies inhibiting virus replication after previous infection of mice with human viruses can have an impact on the interspecies transmission and spread of avian IAV in the human population.

  17. Hepatitis C virus infection can mimic type 1 (antinuclear antibody positive) autoimmune chronic active hepatitis.

    Science.gov (United States)

    Pawlotsky, J M; Deforges, L; Bretagne, S; André, C; Métreau, J M; Thiers, V; Zafrani, E S; Goossens, M; Duval, J; Mavier, J P

    1993-01-01

    Hepatitis C virus (HCV) has been shown to induce anti-liver-kidney microsomal-1 (LKM1) antibody positive chronic active hepatitis, simulating type 2 autoimmune chronic active hepatitis. The cases of five patients presenting with features of type 1 (antinuclear antibody positive) autoimmune chronic active hepatitis and extrahepatic autoimmune manifestations, in whom immunosuppressive treatment had no effect on liver disease are presented. In these patients, HCV infection could be shown by the presence in serum of anti-HCV antibodies and HCV-RNA detected by polymerase chain reaction. These cases suggest the following: (a) chronic HCV infection can mimic type 1, as well as type 2, autoimmune chronic active hepatitis; (b) HCV infection might be systematically sought in patients presenting with features of type 1 autoimmune chronic active hepatitis, with special care in patients who are unresponsive to immunosuppressive treatment. Images Figure PMID:7686122

  18. Role of neutralizing antibodies and T-cells in pathogenesis of herpes simplex virus infection in congenitally athymic mice.

    Science.gov (United States)

    Kapoor, A K; Buckmaster, A; Nash, A A; Field, H J; Wildy, P

    1982-11-01

    Congenitally athymic nude mice were infected with 10(4) p.f.u. herpes simplex type 1 (strain SC16). Following the passive transfer of neutralizing monoclonal antibodies (AP7, AP8 and AP12) it was observed that AP7 alone reduced the virus infectivity in the nervous system; AP8 and AP12 failed to protect mice probably due to poor in vivo binding to the neutralization site on the virus. Latent ganglionic infection could be established in nude mice following adoptive transfer of optimum number (2 x 10(7) cells/mouse) of immune lymph node cells from day 7 herpes virus-infected hairy immunocompetent donor mice. Moreover, in some of the immune lymph node cell protected nudes, latency could be maintained even in complete absence of neutralizing antibodies. Results of ear-ablation experiments revealed that removal of primary source of infection after day 5 of infection reduced the amount of virus in the ganglia and spinal cord. Acute neurological infection was not detected following transfer of protective anti-gp-D neutralizing antibody (LP2) in combination with removal of infected pinna. These data suggest that continuous seeding of virus occurs in related ganglia via the axonal route from infected ear pinna. It appears that local T-cell-mediated immune mechanisms are involved in maintenance of latency.

  19. Antiplasmodial activity of methanolic extract of asparagus officinalis l. stem on plasmodium berghei infected mice

    International Nuclear Information System (INIS)

    Minari, J.B.; Adutuga, A.A.

    2016-01-01

    This study aims at investigating the antiplasmodial activity of methanolic extract of Asparagus officinalis L. stem on Plasmodium berghei infected mice. To investigate this, the mice were infected with P.berghei to cause malaria. The mice were simultaneously given oral doses (20, 40 and 60 mg/kg body weight) of methanolic extract of A. officinalis L. stem. The phytochemical constituents of the extract revealed the presence of alkaloids, phenolics, cardiac glycosides, flavonoids, terpenoid and steroid. The extract administered to the infected mice significantly suppressed the parasite. The extract also significantly (P<0.05) reduced the activities of serum aspatate aminotransferase (AST), alkaline phosphate (ALP), alanine aminotransferase (ALT). White blood corpuscles (WBC), red blood corpuscles (RBC), hemoglobin (HGB), packed cell volume (PCV), platelets (PLT) and the mean corpuscular hemoglobin concentration (MCHC) showed significant (P<0.05) increase after the administration of the extract while mean corpuscular volume (MCV) and the mean corpuscular hemoglobin (MCH) showed significant (P<0.05) reduction. Present findings suggests that the plant extract contains phytochemicals that have antiplasmodial and hepatoprotective properties. (author)

  20. [Intestinal disorder of anaerobic bacteria aggravates pulmonary immune pathological injury of mice infected with influenza virus].

    Science.gov (United States)

    Wu, Sha; Yan, Yuqi; Zhang, Mengyuan; Shi, Shanshan; Jiang, Zhenyou

    2016-04-01

    To investigate the relationship between the intestinal disorder of anaerobic bacteria and influenza virus infection, and the effect on pulmonary inflammatory cytokines in mice. Totally 36 mice were randomly divided into normal control group, virus-infected group and metronidazole treatment group (12 mice in each group). Mice in the metronidazole group were administrated orally with metronidazole sulfate for 8 days causing anaerobic bacteria flora imbalance; then all groups except the normal control group were treated transnasally with influenza virus (50 μL/d FM1) for 4 days to establish the influenza virus-infected models. Their mental state and lung index were observed, and the pathological morphological changes of lung tissues, caecum and intestinal mucosa were examined by HE staining. The levels of interleukin 4 (IL-4), interferon γ (IFN-γ), IL-10 and IL-17 in the lung homogenates were determined by ELISA. Compared with the virus control group, the metronidazole group showed obviously increased lung index and more serious pathological changes of the lung tissue and appendix inflammation performance. After infected by the FM1 influenza virus, IFN-γ and IL-17 of the metronidazole group decreased significantly and IL-4 and IL-10 levels were raised, but there was no statistically difference between the metronidazole and virus control groups. Intestinal anaerobic bacteria may inhibit the adaptive immune response in the lungs of mice infected with FM1 influenza virus through adjusting the lung inflammatory factors, affect the replication and clean-up time of the FM1 influenza virus, thus further aggravating pulmonary immune pathological injury caused by the influenza virus infection.

  1. 5' Rapid Amplification of cDNA Ends and Illumina MiSeq Reveals B Cell Receptor Features in Healthy Adults, Adults With Chronic HIV-1 Infection, Cord Blood, and Humanized Mice.

    Science.gov (United States)

    Waltari, Eric; Jia, Manxue; Jiang, Caroline S; Lu, Hong; Huang, Jing; Fernandez, Cristina; Finzi, Andrés; Kaufmann, Daniel E; Markowitz, Martin; Tsuji, Moriya; Wu, Xueling

    2018-01-01

    Using 5' rapid amplification of cDNA ends, Illumina MiSeq, and basic flow cytometry, we systematically analyzed the expressed B cell receptor (BCR) repertoire in 14 healthy adult PBMCs, 5 HIV-1+ adult PBMCs, 5 cord blood samples, and 3 HIS-CD4/B mice, examining the full-length variable region of μ, γ, α, κ, and λ chains for V-gene usage, somatic hypermutation (SHM), and CDR3 length. Adding to the known repertoire of healthy adults, Illumina MiSeq consistently detected small fractions of reads with high mutation frequencies including hypermutated μ reads, and reads with long CDR3s. Additionally, the less studied IgA repertoire displayed similar characteristics to that of IgG. Compared to healthy adults, the five HIV-1 chronically infected adults displayed elevated mutation frequencies for all μ, γ, α, κ, and λ chains examined and slightly longer CDR3 lengths for γ, α, and λ. To evaluate the reconstituted human BCR sequences in a humanized mouse model, we analyzed cord blood and HIS-CD4/B mice, which all lacked the typical SHM seen in the adult reference. Furthermore, MiSeq revealed identical unmutated IgM sequences derived from separate cell aliquots, thus for the first time demonstrating rare clonal members of unmutated IgM B cells by sequencing.

  2. Development of a Murine Model for Aerosolized Ebolavirus Infection Using a Panel of Recombinant Inbred Mice

    Directory of Open Access Journals (Sweden)

    Malak Kotb

    2012-12-01

    Full Text Available Countering aerosolized filovirus infection is a major priority of biodefense research.  Aerosol models of filovirus infection have been developed in knock-out mice, guinea pigs and non-human primates; however, filovirus infection of immunocompetent mice by the aerosol route has not been reported.  A murine model of aerosolized filovirus infection in mice should be useful for screening vaccine candidates and therapies.  In this study, various strains of wild-type and immunocompromised mice were exposed to aerosolized wild-type (WT or mouse-adapted (MA Ebola virus (EBOV.  Upon exposure to aerosolized WT-EBOV, BALB/c, C57BL/6 (B6, and DBA/2 (D2 mice were unaffected, but 100% of severe combined immunodeficiency (SCID and 90% of signal transducers and activators of transcription (Stat1 knock-out (KO mice became moribund between 7–9 days post-exposure (dpe.  Exposure to MA-EBOV caused 15% body weight loss in BALB/c, but all mice recovered.  In contrast, 10–30% lethality was observed in B6 and D2 mice exposed to aerosolized MA-EBOV, and 100% of SCID, Stat1 KO, interferon (IFN-γ KO and Perforin KO mice became moribund between 7–14 dpe. In order to identify wild-type, inbred, mouse strains in which exposure to aerosolized MA-EBOV is uniformly lethal, 60 BXD (C57BL/6 crossed with DBA/2 recombinant inbred (RI and advanced RI (ARI mouse strains were exposed to aerosolized MA-EBOV, and monitored for disease severity. A complete spectrum of disease severity was observed. All BXD strains lost weight but many recovered. However, infection was uniformly lethal within 7 to 12 days post-exposure in five BXD strains.  Aerosol exposure of these five BXD strains to 10-fold less MA-EBOV resulted in lethality ranging from 0% in two strains to 90–100% lethality in two strains.  Analysis of post-mortem tissue from BXD strains that became moribund and were euthanized at the lower dose of MA-EBOV, showed liver damage in all mice as well as lung lesions in

  3. Chronic voluntary alcohol consumption results in tolerance to sedative/hypnotic and hypothermic effects of alcohol in hybrid mice

    Science.gov (United States)

    Ozburn, Angela Renee; Harris, R. Adron; Blednov, Yuri A.

    2013-01-01

    The continuous two bottle choice test is the most common measure of alcohol consumption but there is remarkably little information about the development of tolerance or dependence with this procedure. We showed that C57BL/6JxFVB/NJ and FVB/NJxC57BL/6J F1 hybrid mice demonstrate greater preference for and consumption of alcohol than either parental strain. In order to test the ability of this genetic model of high alcohol consumption to produce neuroadaptation, we examined development of alcohol tolerance and dependence after chronic self-administration using a continuous access two-bottle choice paradigm. Ethanol-experienced mice stably consumed about 16–18 g/kg/day of ethanol. Ethanol-induced withdrawal severity was assessed (after 59 days of drinking) by scoring handling-induced convulsions; withdrawal severity was minimal and did not differ between ethanol-experienced and -naïve mice. After 71 days of drinking, the rate of ethanol clearance was similar for ethanol-experienced and -naïve mice. After 77 days of drinking, ethanol-induced loss of righting reflex (LORR) was tested daily for 5 days. Ethanol-experienced mice had a shorter duration of LORR. For both ethanol-experienced and -naïve mice, blood ethanol concentrations taken at gain of righting reflex were greater on day 5 than on day 1, indicative of tolerance. After 98 days of drinking, ethanol-induced hypothermia was assessed daily for 3 days. Both ethanol-experienced and –naïve mice developed rapid and chronic tolerance to ethanol-induced hypothermia, with significant group differences on the first day of testing. In summary, chronic, high levels of alcohol consumption in F1 hybrid mice produced rapid and chronic tolerance to both the sedative/hypnotic and hypothermic effects of ethanol; additionally, a small degree of metabolic tolerance developed. The development of tolerance supports the validity of using this model of high alcohol consumption in genetic studies of alcoholism. PMID:23313769

  4. Chronic Pseudomonas aeruginosa infection definition: EuroCareCF Working Group report

    DEFF Research Database (Denmark)

    Pressler, T; Bohmova, C; Conway, S

    2011-01-01

    are particularly challenging: the progressive nature of the disease and the wide variation in severity influence considerably the outcome of drug testing. A validated, universally accepted, and clinically useful classification of patients infected with P. aeruginosa, particularly those chronically infected...

  5. Zika Virus Infection in Mice Causes Panuveitis with Shedding of Virus in Tears.

    Science.gov (United States)

    Miner, Jonathan J; Sene, Abdoulaye; Richner, Justin M; Smith, Amber M; Santeford, Andrea; Ban, Norimitsu; Weger-Lucarelli, James; Manzella, Francesca; Rückert, Claudia; Govero, Jennifer; Noguchi, Kevin K; Ebel, Gregory D; Diamond, Michael S; Apte, Rajendra S

    2016-09-20

    Zika virus (ZIKV) is an emerging flavivirus that causes congenital abnormalities and Guillain-Barré syndrome. ZIKV infection also results in severe eye disease characterized by optic neuritis, chorioretinal atrophy, and blindness in newborns and conjunctivitis and uveitis in adults. We evaluated ZIKV infection of the eye by using recently developed mouse models of pathogenesis. ZIKV-inoculated mice developed conjunctivitis, panuveitis, and infection of the cornea, iris, optic nerve, and ganglion and bipolar cells in the retina. This phenotype was independent of the entry receptors Axl or Mertk, given that Axl(-/-), Mertk(-/-), and Axl(-/-)Mertk(-/-) double knockout mice sustained levels of infection similar to those of control animals. We also detected abundant viral RNA in tears, suggesting that virus might be secreted from lacrimal glands or shed from the cornea. This model provides a foundation for studying ZIKV-induced ocular disease, defining mechanisms of viral persistence, and developing therapeutic approaches for viral infections of the eye. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  6. Dietary supplementation of resveratrol attenuates chronic colonic inflammation in mice.

    Science.gov (United States)

    Sánchez-Fidalgo, Susana; Cárdeno, Ana; Villegas, Isabel; Talero, Elena; de la Lastra, Catalina Alarcón

    2010-05-10

    Ulcerative colitis is a nonspecific inflammatory disorder characterized by oxidative and nitrosative stress, leucocyte infiltration and upregulation of inflammatory mediators. Resveratrol is a polyphenolic compound found in grapes and wine, with multiple pharmacological actions, mainly anti-inflammatory, antioxidant, antitumour and immunomodulatory activities. The aim of this study was to investigate the effect of dietary resveratrol on chronic dextran sulphate sodium (DSS)-induced colitis. Six-week-old mice were randomized into two dietary groups: one standard diet and the other enriched with resveratrol at 20mg/kg of diet. After 30days, mice were exposed to 3% DSS for 5days developing acute colitis that progressed to severe chronic inflammation after 21days of water. Our results demonstrated that resveratrol group significantly attenuated the clinical signs such as loss of body weight, diarrhea and rectal bleeding improving results from disease activity index and inflammatory score. Moreover, the totality of resveratrol-fed animals survived and finished the treatment while animals fed with standard diet showed a mortality of 40%. Three weeks after DSS removal, the polyphenol caused substantial reductions of the rise of pro-inflammatory cytokines, TNF-alpha and IL-1beta and an increase of the anti-inflammatory cytokine IL-10. Also resveratrol reduced prostaglandin E synthase-1 (PGES-1), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) proteins expression, via downregulation of p38, a mitogen-activated protein kinases (MAPK) signal pathway. We conclude that resveratrol diet represents a novel approach to the treatment of chronic intestinal inflammation. Copyright 2010 Elsevier B.V. All rights reserved.

  7. Cognitive deficits associated with combined HIV gp120 expression and chronic methamphetamine exposure in mice

    Science.gov (United States)

    Kesby, James P.; Markou, Athina; Semenova, Svetlana

    2014-01-01

    Methamphetamine abuse is common among individuals infected by human immunodeficiency virus (HIV). Neurocognitive outcomes tend to be worse in methamphetamine users with HIV. However, it is unclear whether discrete cognitive domains are susceptible to impairment after combined HIV infection and methamphetamine abuse. The expression of HIV/gp120 protein induces neuropathology in mice similar to HIV-induced pathology in humans. We investigated the separate and combined effects of methamphetamine exposure and gp120 expression on cognitive function in transgenic (gp120-tg) and control mice. The mice underwent an escalating methamphetamine binge regimen and were tested in novel object/location recognition, object-in-place recognition, and Barnes maze tests. gp120 expression disrupted performance in the object-in-place test (i.e., similar time spent with all objects, regardless of location), indicating deficits in associative recognition memory. gp120 expression also altered reversal learning in the Barnes maze, suggesting impairments in executive function. Methamphetamine exposure impaired spatial strategy in the Barnes maze, indicating deficits in spatial learning. Methamphetamine-exposed gp120-tg mice had the lowest spatial strategy scores in the final acquisition trials in the Barnes maze, suggesting greater deficits in spatial learning than all of the other groups. Although HIV infection involves interactions between multiple proteins and processes, in addition to gp120, our findings in gp120-tg mice suggest that humans with the dual insult of HIV infection and methamphetamine abuse may exhibit a broader spectrum of cognitive deficits than those with either factor alone. Depending on the cognitive domain, the combination of both insults may exacerbate deficits in cognitive performance compared with each individual insult. PMID:25476577

  8. Adaptation and possible attenuation of Theileria parva-infected cells grown in irradiated mice

    International Nuclear Information System (INIS)

    Irvin, A.D.; Brown, C.G.D.; Stagg, D.A.; Kanhai, G.K.; Kimber, C.D.; Radley, D.E.

    1976-01-01

    Theileria parva-infected bovine lymphoid cells were taken from 8 cattle immediately after death from East Coast fever (ECF). Cells were inoculated into groups of irradiated Swiss and athymic nude mice. The irradiated mice were exposed to 800 rad doses from a 60 Co source. Cells became established in one group of Swiss mice and 2 groups of athymic mice. Development of cells in mice only occurred if cells concurrently established in culture; when establishment in culture was delayed, cells failed to develop in mice. Cells from one of the isolates in athymic mice were passaged 6 times through further mice. On inoculation of these mouse-passaged cells into cattle, the animals underwent mild reactions and subsequently resisted a lethal ECF challenge. The possibility of vaccinating cattle aginst ECF by means of mouse passaged cells merits further study. (author)

  9. Intravascular detection of Giardia trophozoites in naturally infected mice

    Directory of Open Access Journals (Sweden)

    El-Shewy K.A.

    2003-06-01

    Full Text Available During routine transmission electron microscopic (TEM examination of mice naturally infected with Giardia muris, an intense infection with Giardia trophozoites was demonstrated within intestinal and renal tissues. Examination of randomly taken sections from these heavily infected tissues revealed marked deep affection with mixed pathology. Duodenal sections were found loaded with Giardia trophozoites in intimate contact with necrotic gut cells. Some of these trophozoites were detected within central lacteal of damaged villi and nearby blood vessels. Interestingly, and for the first time to be demonstrated, morphologically identical G. muris trophozoite was detected in a renal blood vessel. An intense cellular immune reaction was obviously demonstrated with remarkable interaction between giant macrophages and the trophozoites particulates. Involvement of deep tissues by Giardia trophozoites and their presence within vascular channels could open up questions about the possible invasive and disseminative behavior of G. muris, particularly in heavily and naturally infected hosts.

  10. Zika Virus Infection during Pregnancy in Mice Causes Placental Damage and Fetal Demise.

    Science.gov (United States)

    Miner, Jonathan J; Cao, Bin; Govero, Jennifer; Smith, Amber M; Fernandez, Estefania; Cabrera, Omar H; Garber, Charise; Noll, Michelle; Klein, Robyn S; Noguchi, Kevin K; Mysorekar, Indira U; Diamond, Michael S

    2016-05-19

    Zika virus (ZIKV) infection in pregnant women causes intrauterine growth restriction, spontaneous abortion, and microcephaly. Here, we describe two mouse models of placental and fetal disease associated with in utero transmission of ZIKV. Female mice lacking type I interferon signaling (Ifnar1(-/-)) crossed to wild-type (WT) males produced heterozygous fetuses resembling the immune status of human fetuses. Maternal inoculation at embryonic day 6.5 (E6.5) or E7.5 resulted in fetal demise that was associated with ZIKV infection of the placenta and fetal brain. We identified ZIKV within trophoblasts of the maternal and fetal placenta, consistent with a trans-placental infection route. Antibody blockade of Ifnar1 signaling in WT pregnant mice enhanced ZIKV trans-placental infection although it did not result in fetal death. These models will facilitate the study of ZIKV pathogenesis, in utero transmission, and testing of therapies and vaccines to prevent congenital malformations. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. An efficient chronic unpredictable stress protocol to induce stress-related responses in C57BL/6 mice.

    Science.gov (United States)

    Monteiro, Susana; Roque, Susana; de Sá-Calçada, Daniela; Sousa, Nuno; Correia-Neves, Margarida; Cerqueira, João José

    2015-01-01

    Exposure to chronic stress can have broad effects on health ranging from increased predisposition for neuropsychiatric disorders to deregulation of immune responses. The chronic unpredictable stress (CUS) protocol has been widely used to study the impact of stress exposure in several animal models and consists in the random, intermittent, and unpredictable exposure to a variety of stressors during several weeks. CUS has consistently been shown to induce behavioral and immunological alterations typical of the chronic stress-response. Unfortunately C57BL/6 mice, one of the most widely used mouse strains, due to the great variety of genetically modified lines, seem to be resistant to the commonly used 4-week-long CUS protocol. The definition of an alternative CUS protocol allowing the use of C57BL/6 mice in chronic stress experiments is a need. Here, we show that by extending the CUS protocol to 8 weeks is possible to induce a chronic stress-response in C57BL/6 mice, as revealed by abrogated body weight gain, increased adrenals weight, and an overactive hypothalamic-pituitary-adrenal axis with increased levels of serum corticosterone. Moreover, we also observed stress-associated behavioral alterations, including the potentiation of anxious-like and depressive-like behaviors and a reduction of exploratory behavior, as well as subtle stress-related changes in the cell population of the thymus and of the spleen. The present protocol for C57BL/6 mice consistently triggers the spectrum of CUS-induced changes observed in rats and, thus, will be highly useful to researchers that need to use this particular mouse strain as an animal model of neuropsychiatric disorders and/or immune deregulation related to CUS.

  12. Effects of Mirazid Treatment and Vaccination with Irradiated Cercariae in Experimentally Schistosoma mansoni Infected Mice

    International Nuclear Information System (INIS)

    Fayad, M.E.; Moawad, M.A.; Abd El-Fattah, N.Se.

    2006-01-01

    Schistosomiasis Tops all the endemic parasitic diseases particularly in Egypt. This study was performed on 4 groups of mice, each group formed of 25 mice. Group 1 (control group) infected with Schistosoma mansoni cercariae, group 2 (vaccinated group) vaccinated with irradiated cercariae, group 3 (treated group) infected with living cercariae of Schistosoma mansoni, then treated with Mirazid in the day post infection and group 4 (vaccinated and treated group) vaccinated with irradiated cercariae of Schistosoma mansoni then challenged and treated with Mirazid in the day post infection. By comparing the results of group 4 (vaccinated and treated group) with respective control there was a highly significant difference in all parameters. The worm burden reduction was 100 % and the percentage reduction of the eggs in the liver was 96.6 % and in the intestine was 89.76 %. Also, there were marked reduction in the size and number of granulomas with preservation of the liver architecture and absence of areas of degeneration and necrosis. So, this study shown that resistance to schistosomiasis can be consistently induced in mice by combining drug therapy with vaccination

  13. Adverse Events Post Smallpox-Vaccination: Insights from Tail Scarification Infection in Mice with Vaccinia virus

    Science.gov (United States)

    Mota, Bruno E. F.; Gallardo-Romero, Nadia; Trindade, Giliane; Keckler, M. Shannon; Karem, Kevin; Carroll, Darin; Campos, Marco A.; Vieira, Leda Q.; da Fonseca, Flávio G.; Ferreira, Paulo C. P.; Bonjardim, Cláudio A.; Damon, Inger K.; Kroon, Erna G.

    2011-01-01

    Adverse events upon smallpox vaccination with fully-replicative strains of Vaccinia virus (VACV) comprise an array of clinical manifestations that occur primarily in immunocompromised patients leading to significant host morbidity/mortality. The expansion of immune-suppressed populations and the possible release of Variola virus as a bioterrorist act have given rise to concerns over vaccination complications should more widespread vaccination be reinitiated. Our goal was to evaluate the components of the host immune system that are sufficient to prevent morbidity/mortality in a murine model of tail scarification, which mimics immunological and clinical features of smallpox vaccination in humans. Infection of C57BL/6 wild-type mice led to a strictly localized infection, with complete viral clearance by day 28 p.i. On the other hand, infection of T and B-cell deficient mice (Rag1 −/−) produced a severe disease, with uncontrolled viral replication at the inoculation site and dissemination to internal organs. Infection of B-cell deficient animals (µMT) produced no mortality. However, viral clearance in µMT animals was delayed compared to WT animals, with detectable viral titers in tail and internal organs late in infection. Treatment of Rag1 −/− with rabbit hyperimmune anti-vaccinia serum had a subtle effect on the morbidity/mortality of this strain, but it was effective in reduce viral titers in ovaries. Finally, NUDE athymic mice showed a similar outcome of infection as Rag1 −/−, and passive transfer of WT T cells to Rag1 −/− animals proved fully effective in preventing morbidity/mortality. These results strongly suggest that both T and B cells are important in the immune response to primary VACV infection in mice, and that T-cells are required to control the infection at the inoculation site and providing help for B-cells to produce antibodies, which help to prevent viral dissemination. These insights might prove helpful to better identify

  14. Comparison of the course of infection with Giardia muris in male and female mice.

    Science.gov (United States)

    Daniels, C W; Belosevic, M

    1995-01-01

    The infection with Giardia muris in male and female C57BL/6 mice was characterized by enumerating cyst release in the feces and trophozoite burden in the small intestine. Cyst release differed between males and females during the course of the primary and challenge infections. Males and females released similar numbers of cysts in the feces during the acute phase of the infection. However, the trophozoite burden was significantly higher in males during the same period. Males released cysts in their feces longer than females and trophozoites present in their intestines for a longer period than females. From day 18 of infection the females did not release cysts in their feces, while males continued to do so for at least 60 days. Thus, distinct differences exist between male and female mice in their ability to harbor and eliminate this intestinal parasite.

  15. The nervous system in genital herpes simplex virus type 2 infections in mice. Lethal panmyelitis or nonlethal demyelinative myelitis or meningitis.

    Science.gov (United States)

    Martin, J R; Stoner, G L

    1984-11-01

    Female mice were inoculated vaginally with the MS strain of herpes simplex virus type 2, and serially positive vaginal cultures were used to confirm infection. The proportion of mice infected and the mortality rate in infected mice decreased with increasing age. In mice 12 weeks old, clinical, neuropathologic, and virologic criteria defined four patterns of disease. Moribund mice had severe genital lesions, hindleg paralysis, and urinary and fecal retention, and most died during the second week of infection. These mice had a panmyelitis with a decreasing gradient of both viral antigen and lesions extending rostrally from the lumbosacral cord into the brain stem. Lesions were about equally distributed in gray and white matter and were characterized by neuronal loss and axonal demyelination, respectively. By contrast, mice with nonfatal infections had mild or no evident genital lesions and a small proportion had mild hindleg weakness. Of these, some mice had demyelinative lesions, particularly in the lower spinal cord but also at higher cord and brain stem levels, whereas others had leptomeningitis. Both of these groups had sacral sensory root abnormalities. A third group of survivors lacked both sensory root and central nervous system abnormalities. This report defines a broader spectrum of disease patterns following infection by a natural route than has been previously appreciated. It provides the first evidence that nonfatal herpes simplex virus type 2 infection by a peripheral route can produce central nervous system demyelination. It indicates that in aseptic meningitis with this agent, the route of virus spread to the central nervous system is neural and not hematogenous. Finally, the antigenic and pathologic observations presented here complement and confirm the virus isolation data and pathologic findings of others that genital herpes simplex virus type 2 infection causes ascending infection in the peripheral and central nervous system.

  16. Clinical and epidemiological features of patients with chronic hepatitis C co-infected with HIV

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    Braga Eduardo Lorens

    Full Text Available Co-infection with hepatitis C virus (HCV and human immunodeficiency virus (HIV is increasingly common and affects the clinical course of chronic hepatitis C. Highly active antiretroviral therapy has improved the life expectancy of HIV infected patients, but, by extending survival, it permits the development of HCV cirrhosis. This study tried to evaluate clinical and epidemiological features of patients with chronic hepatitis C co-infected with HIV. We evaluated 134 HCV-infected patients: i group A - 65 co-infected HCV/HIV patients, ii group B - 69 mono-infected HCV patients. The impact of HIV infection on HCV liver disease was analyzed using Child's score, ultrasound findings and liver histology. Patients were subjected to HCV genotyping and anti-HBs dosage. Patients mean age was 42.4 years (±9.1 and 97 (72.4% were males. Injected drug use and homo/bisexual practice were more frequently encountered in the co-infected group: 68.3% and 78.0%, respectively. Antibodies against hepatitis B virus (anti-HBs were found in only 38.1% of the patients (66.7% group A x 33.3% group B. Ten out of 14 individuals (71.4% who had liver disease (Child B or C and 25 out of 34 (73.5% who showed ultrasound evidence of chronic liver disease were in the co-infection group. HCV genotype-2/3 was more frequently encountered in co-infected patients (36.9% group A vs. 21.8% group B. Conclusions: a HIV infection seems to adversely affect the clinical course of chronic hepatitis C, b injected drug use, bi/homosexual practice and genotype-2/3 were more frequently encountered in co-infected patients, c immunization against HBV should be encouraged in these patients.

  17. Pharmacokinetic of antimony in mice with cutaneous Leishmaniasis

    Energy Technology Data Exchange (ETDEWEB)

    Borborema, Samanta E.T.; Nascimento, Nanci do [Instituto de Pesquisas Energeticas e Nucleares IPEN/CNEN-SP, Sao Paulo, SP (Brazil). Lab. de Biologia Molecular]. E-mails: samanta@usp.br; nnascime@ipen.br; Andrade Junior, Heitor F. de [Instituto de Pesquisas Energeticas e Nucleares IPEN/CNEN-SP, Sao Paulo, SP (Brazil). Lab. de Biologia Molecular; Instituto de Medicina Tropical de Sao Paulo, Sao Paulo, SP (Brazil); E-mail: hfandrad@usp.br; Osso Junior, Joao A. [Instituto de Pesquisas Energeticas e Nucleares IPEN/CNEN-SP, Sao Paulo, SP (Brazil). Centro de Radiofarmacia]. E-mail: jaosso@ipen.br

    2007-07-01

    Cutaneous Leishmaniasis (CL) remains a major world health problem, with about 1.5 million new cases each year. Caused by protozoa Leishmania, in South America, this infection can vary from a chronic skin ulcer, to an erosive mucosal disease and severe facial disfigurement. Pentavalent antimony (Sb{sup +5}) as sodium stibogluconate (Pentostam) or meglumine antimoniate (Glucantime) are main drugs for treating most forms of human leishmaniasis. For six decades, despite the recent developments, the effective therapy to cutaneous leishmaniasis has been based on long parenteral courses of such drugs, even though these are fairly costly, toxic and inconvenient to use, without adequate knowledge on their pharmacokinetics or mechanism of action. Pharmacokinetics studies could be based on bioactive traceable drugs, usually with radioactive isotopes, but antimony radioisotopes are unavailable commercially. Neutron irradiation is a powerful tool in the analysis of mineral content of samples, for antimony, there are at least two main isotopes that could be formed after neutron irradiation in nuclear reactor. The aim of the present study was to construct antimony salts with those radioisotopes to obtain tracers to compare the pharmacokinetic and the tissue distribution of neutron irradiated meglumine antimoniate in healthy and cutaneous leishmaniasis experimentally infected mice. Meglumine antimoniate, (Glucantime, Aventis, S.P, Brazil), was neutron irradiated inside the IEA-R1 nuclear reactor (IPEN/CNEN-SP), producing two radioisotopes {sup 122}Sb and {sup 124}Sb. Its biodistribution was verified in BALB/c mice experimentally infected with Leishmania (Leishmania) Amazonensis, which received a single intraperitoneal dose of the drug. At different times after injection, the tissues and blood were excised and activity measured in a NaI (Tl) scintillation counter. Compared with the healthy mice, experimentally infected mice had significantly lower maximum concentration of antimony

  18. Pharmacokinetic of antimony in mice with cutaneous Leishmaniasis

    International Nuclear Information System (INIS)

    Borborema, Samanta E.T.; Nascimento, Nanci do; Osso Junior, Joao A.

    2007-01-01

    Cutaneous Leishmaniasis (CL) remains a major world health problem, with about 1.5 million new cases each year. Caused by protozoa Leishmania, in South America, this infection can vary from a chronic skin ulcer, to an erosive mucosal disease and severe facial disfigurement. Pentavalent antimony (Sb +5 ) as sodium stibogluconate (Pentostam) or meglumine antimoniate (Glucantime) are main drugs for treating most forms of human leishmaniasis. For six decades, despite the recent developments, the effective therapy to cutaneous leishmaniasis has been based on long parenteral courses of such drugs, even though these are fairly costly, toxic and inconvenient to use, without adequate knowledge on their pharmacokinetics or mechanism of action. Pharmacokinetics studies could be based on bioactive traceable drugs, usually with radioactive isotopes, but antimony radioisotopes are unavailable commercially. Neutron irradiation is a powerful tool in the analysis of mineral content of samples, for antimony, there are at least two main isotopes that could be formed after neutron irradiation in nuclear reactor. The aim of the present study was to construct antimony salts with those radioisotopes to obtain tracers to compare the pharmacokinetic and the tissue distribution of neutron irradiated meglumine antimoniate in healthy and cutaneous leishmaniasis experimentally infected mice. Meglumine antimoniate, (Glucantime, Aventis, S.P, Brazil), was neutron irradiated inside the IEA-R1 nuclear reactor (IPEN/CNEN-SP), producing two radioisotopes 122 Sb and 124 Sb. Its biodistribution was verified in BALB/c mice experimentally infected with Leishmania (Leishmania) Amazonensis, which received a single intraperitoneal dose of the drug. At different times after injection, the tissues and blood were excised and activity measured in a NaI (Tl) scintillation counter. Compared with the healthy mice, experimentally infected mice had significantly lower maximum concentration of antimony and high

  19. Effect of cold water-induced stress on immune response, pathology and fertility in mice during Chlamydia muridarum genital infection.

    Science.gov (United States)

    Belay, Tesfaye; Woart, Anthony; Graffeo, Vincent

    2017-07-31

    Genital infection by Chlamydia trachomatis is the most common bacterial sexually transmitted disease worldwide. It causes serious reproductive health complications, including pelvic inflammatory disease and infertility. Stress is implicated as a risk factor for various infections; however, its effect on chlamydia genital infection is unknown. We previously showed that repeated exposure of mice to cold water results in increased severity of chlamydia genital infection. In this study, cold water-induced stress resulted in (i) elevated levels of norepinephrine (NE) and epinephrine in the spleen and genital tract of stressed mice; (ii) elevated IL-1β, TNF-α, IL-6 and nitric oxide production in macrophage-rich peritoneal cells of mice; (iii) supplement of NE in vitro exerts an immunosuppressive effect on splenic T-cell production of cytokines; (iv) decreased C. muridarum shedding in the genital tract of β1Adr/β2Adr receptor KO mice; and (v) a higher rate of infertility in infected mice. These results suggest that cold water stress induces the production of catecholamines, which may play a critical role in the modulation of the immune system leading to increased intensity of C. muridarum genital infection. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Persistence of Tetracapsuloides bryosalmonae (Myxozoa) in chronically infected brown trout Salmo trutta.

    Science.gov (United States)

    Abd-Elfattah, Ahmed; Kumar, Gokhlesh; Soliman, Hatem; El-Matbouli, Mansour

    2014-08-21

    Proliferative kidney disease (PKD) is a widespread disease of farmed and wild salmonid populations in Europe and North America, caused by the myxozoan parasite Tetracapsuloides bryosalmonae. Limited studies have been performed on the epidemiological role in spread of the disease played by fish that survive infection with T. bryosalmonae. The aim of the present study was to evaluate the persistence of T. bryosalmonae developmental stages in chronically infected brown trout Salmo trutta up to 2 yr after initial exposure to laboratory-infected colonies of the parasite's alternate host, the bryozoan Fredericella sultana. Kidney, liver, spleen, intestine, brain, gills and blood were sampled 24, 52, 78 and 104 wk post-exposure (wpe) and tested for T. bryosalmonae by PCR and immunohistochemistry (IHC). Cohabitation trials with specific pathogen free (SPF) F. sultana colonies were conducted to test the viability of T. bryosalmonae. PCR detected T. bryosalmonae DNA in all tissue samples collected at the 4 time points. Developmental stages of T. bryosalmonae were demonstrated by IHC in most samples at the 4 time points. Cohabitation of SPF F. sultana with chronically infected brown trout resulted in successful transmission of T. bryosalmonae to the bryozoan. This study verified the persistence of T. bryosalmonae in chronically infected brown trout and their ability to infect the bryozoan F. sultana up to 104 wpe.

  1. Hepatitis C virus quasispecies and pseudotype analysis from acute infection to chronicity in HIV-1 co-infected individuals.

    Science.gov (United States)

    Ferns, R Bridget; Tarr, Alexander W; Hue, Stephane; Urbanowicz, Richard A; McClure, C Patrick; Gilson, Richard; Ball, Jonathan K; Nastouli, Eleni; Garson, Jeremy A; Pillay, Deenan

    2016-05-01

    HIV-1 infected patients who acquire HCV infection have higher rates of chronicity and liver disease progression than patients with HCV mono-infection. Understanding early events in this pathogenic process is important. We applied single genome sequencing of the E1 to NS3 regions and viral pseudotype neutralization assays to explore the consequences of viral quasispecies evolution from pre-seroconversion to chronicity in four co-infected individuals (mean follow up 566 days). We observed that one to three founder viruses were transmitted. Relatively low viral sequence diversity, possibly related to an impaired immune response, due to HIV infection was observed in three patients. However, the fourth patient, after an early purifying selection displayed increasing E2 sequence evolution, possibly related to being on suppressive antiretroviral therapy. Viral pseudotypes generated from HCV variants showed relative resistance to neutralization by autologous plasma but not to plasma collected from later time points, confirming ongoing virus escape from antibody neutralization. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Interaction of TLR-IFN and HLA polymorphisms on susceptibility of chronic HBV infection in Southwest Han Chinese.

    Science.gov (United States)

    He, Dengming; Tao, Shiqi; Guo, Shimin; Li, Maoshi; Wu, Junqiu; Huang, Hongfei; Guo, Xinwu; Yan, Guohua; Zhu, Peng; Wang, Yuming

    2015-08-01

    The toll-like receptor-interferon (TLR-IFN) signalling pathway plays a crucial role in HBV infection. Human leucocyte antigen (HLA) polymorphisms are associated with chronic HBV infection by genome wide association study (GWAS). We aimed to explore interaction between TLR-IFN and HLA gene polymorphisms in susceptibility of chronic HBV infection. In the Chinese Southwest Han population, 1191 chronic HBV infection patients and 273 HBV clearance were selected. A total of 39 single nucleotide polymorphism loci in 23 genes of the TLR-IFN pathway and four HLA polymorphism loci associated with chronic HBV infection identified by GWAS were selected for genotyping. SNPStats, QVALUE, and multifactor dimensionality reduction were used for statistical analysis. A significant association was seen in several of the TLR-IFN pathway genes, TLR9 rs352140 (OR = 0.70, P = 0.0088), IL1B rs16944 (OR = 0.67, P = 0.016), IL12B rs3212227 (OR = 1.38, P = 0.021), IFNGR1 rs3799488 (OR = 1.48, P = 0.0048), IFNGR2 rs1059293 (OR = 0.27, P = 0.011), MX1 rs467960 (OR = 0.68, P = 0.022), as well as four loci in HLA, rs3077 (OR = 0.55, P rs16944 (0.13%), rs1143623 and rs6613 (0.10%). The combination of rs9277535 in HLA and rs16944 in IL1B was the best model to predict chronic HBV infection (testing accuracy = 0.6040, P = 0.0010, cross-validation consistency = 10/10). TLR-IFN pathway gene polymorphisms are associated with chronic HBV infection. Interactions with polymorphisms in these genes may be one mechanism by which HLA polymorphisms influence susceptibility to chronic HBV infection, as specific single nucleotide polymorphism combinations are highly predictive of chronic HBV infection. © 2014 The Authors. Liver International Published by John Wiley & Sons Ltd.

  3. Detection of Toxoplasma gondii DNA in sera samples of mice experimentally infected

    Directory of Open Access Journals (Sweden)

    H. Langoni

    2006-04-01

    Full Text Available Detection of Toxoplasma gondii (T. gondii DNA in blood can help to diagnose the disease in its acute phase; however, it must be considered that hemoglobin, present in blood, can inhibit polymerase activity, making impracticable the detection of DNA in samples. Mice were experimentally infected via oral route with ME49 and BTU2 strains cysts and RH strain tachyzoites; polymerase chain reaction was used to detect T. gondii DNA in mice sera 18, 24, 48, 96, and 192 hours post infection (PI. Toxoplama gondii DNA was detected in only one animal infected with BTU2 strain, genotype III (isolated from a dog with neurological signs 18 hours PI. The agent's DNA was not detected in any sample of the other experimental groups. New studies must be carried out to verify the technique sensitivity in researches on this agent's genetic material using sera samples of acute-phase toxoplasmosis patients, especially in cases of immunosuppression.

  4. The protective effect of Moringa oleifera leaf extract on liver damage in mice infected with Plasmodium berghei ANKA

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    Kittiyaporn Dondee

    2016-09-01

    Full Text Available Objective: To investigate the protective effect of Moringa oleifera leaf extract on liver damage in mice infected with Plasmodium berghei ANKA (P. berghei Methods: For extraction of Moringa oleifera (M. oleifera leaves, microwave with hot water method was used and acute toxicity study was then be done. Standard Peters’ test was carried out to test the efficacy of M. oleifera extract in vivo. The ICR mice were inoculated with 1 × 107 red blood cells infected with P. berghei strain by intraperitoneal injection. They were subsequently given with 100, 500 and 1000 mg/kg of this extract by intragastric route once a day for 4 consecutive days. Parasitemia was estimated using microscopy and levels of aspartate aminotransferase, alanine aminotransferase and albumin were also measured. Results: The M. oleifera leaf extract showed the protective activity on liver damage in mice infected with P. berghei in a dose-dependent fashion. It can be indicated by normal levels of aspartate aminotransferase, alanine aminotransferase and albumin in mice treated with extract. The 1000 mg/kg of extract was observed to present the highest activity. Interestingly, the dosedependent antimalarial activity was also found in the mice treated with extract. Conclusions: The M. oleifera leaf extract presented protective effect on liver damage in mice infected with P. berghei.

  5. Dietary Chitosan Supplementation Increases Microbial Diversity and Attenuates the Severity of Citrobacter rodentium Infection in Mice

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    Guiping Guan

    2016-01-01

    Full Text Available C57BL/6 mice were tested in order to investigate the effects of dietary chitosan (COS supplements on intestinal microflora and resistance to Citrobacter rodentium infection. The findings reveal that, after consuming a 300 mg/kg COS diet for 14 days, microflora became more diverse as a result of the supplement. Mice receiving COS exhibited an increase in the percentage of Bacteroidetes phylum and a decrease in the percentage of Firmicutes phylum. After Citrobacter rodentium infection, the histopathology scores indicated that COS feeding resulted in less severe colitis. IL-6 and TNF-α were significantly lower in colon from COS-feeding mice than those in the control group. Furthermore, mice in COS group were also found to experience inhibited activation of nuclear factor-kappa B (NF-κB in the colonic tissue. Overall, the findings revealed that adding 300 mg/kg COS to the diet changed the composition of the intestinal microflora of mice, resulting in suppressed NF-κB activation and less production of TNF-α and IL-6; and these changes led to better control of inflammation and resolution of infection with C. rodentium.

  6. Exercise Improves Host Response to Influenza Viral Infection in Obese and Non-Obese Mice through Different Mechanisms

    Science.gov (United States)

    Warren, Kristi J.; Olson, Molly M.; Thompson, Nicholas J.; Cahill, Mackenzie L.; Wyatt, Todd A.; Yoon, Kyoungjin J.; Loiacono, Christina M.; Kohut, Marian L.

    2015-01-01

    Obesity has been associated with greater severity of influenza virus infection and impaired host defense. Exercise may confer health benefits even when weight loss is not achieved, but it has not been determined if regular exercise improves immune defense against influenza A virus (IAV) in the obese condition. In this study, diet-induced obese mice and lean control mice exercised for eight weeks followed by influenza viral infection. Exercise reduced disease severity in both obese and non-obese mice, but the mechanisms differed. Exercise reversed the obesity-associated delay in bronchoalveolar-lavage (BAL) cell infiltration, restored BAL cytokine and chemokine production, and increased ciliary beat frequency and IFNα-related gene expression. In non-obese mice, exercise treatment reduced lung viral load, increased Type-I-IFN-related gene expression early during infection, but reduced BAL inflammatory cytokines and chemokines. In both obese and non-obese mice, exercise increased serum anti-influenza virus specific IgG2c antibody, increased CD8+ T cell percentage in BAL, and reduced TNFα by influenza viral NP-peptide-responding CD8+ T cells. Overall, the results suggest that exercise “restores” the immune response of obese mice to a phenotype similar to non-obese mice by improving the delay in immune activation. In contrast, in non-obese mice exercise treatment results in an early reduction in lung viral load and limited inflammatory response. PMID:26110868

  7. Chronic Ethanol Consumption in Mice Alters Hepatocyte Lipid Droplet Properties

    Science.gov (United States)

    Orlicky, David J.; Roede, James R.; Bales, Elise; Greenwood, Carrie; Greenberg, Andrew; Petersen, Dennis; McManaman, James L.

    2014-01-01

    Background Hepatosteatosis is a common pathological feature of impaired hepatic metabolism following chronic alcohol consumption. Although often benign and reversible, it is widely believed that steatosis is a risk factor for development of advanced liver pathologies, including steatohepatitis and fibrosis. The hepatocyte alterations accompanying the initiation of steatosis are not yet clearly defined. Methods Induction of hepatosteatosis by chronic ethanol consumption was investigated using the Lieber-DeCarli (LD) high fat diet model. Effects were assessed by immunohistochemistry and blood and tissue enzymatic assays. Cell culture models were employed for mechanistic studies. Results Pair feeding mice ethanol (LD-Et) or isocaloric control (LD-Co) diets for 6 weeks progressively increased hepatocyte triglyceride accumulation in morphological, biochemical, and zonally distinct cytoplasmic lipid droplets (CLD). The LD-Et diet induced zone 2-specific triglyceride accumulation in large CLD coated with perilipin, adipophilin (ADPH), and TIP47. In LD-Co- fed mice, CLD were significantly smaller than those in LD-Et-fed mice and lacked perilipin. A direct role of perilipin in formation of large CLD was further suggested by cell culture studies showing that perilipin-coated CLD were significantly larger than those coated with ADPH or TIP47. LD-Co- and LD-Et-fed animals also differed in hepatic metabolic stress responses. In LD-Et but not LD-Co-fed mice, inductions were observed in the following: microsomal ethanol-oxidizing system [cytochrome P-4502E1 (CYP2E1)], hypoxia response pathway (hypoxia-inducible factor 1 alpha, HIF1α), endoplasmic reticulum stress pathway (calreticulin), and synthesis of lipid peroxidation products [4-hydroxynonenal (4-HNE)]. CYP2E1 and HIF1 α immunostaining localized to zone 3 and did not correlate with accumulation of large CLD. In contrast, calreticulin and 4-HNE immunostaining closely correlated with large CLD accumulation. Importantly, 4

  8. Immunological tolerance to lymphocytic choriomeningitis virus in neonatally infected virus carrier mice: evidence supporting a clonal inactivation mechanism

    International Nuclear Information System (INIS)

    Cihak, J.; Lehmann-Grube, F.

    1978-01-01

    Experiments are described aimed at analysing the mechanism responsible for the absence of cell-mediated immunity against LCM virus-infected cells in neonatally established LCM virus carrier mice. Virus-specific cell-mediated immunity was assessed by 51 Cr release and target cell reduction assays. Attempts to demonstrate cells in spleens of CBA/J carrier mice able to suppress in syngeneic recipients the induction or the effector phase of the cytotoxic T-cell response against LCM virus-infected cells were unsuccessful. Also, no factors were detected in CBA/J and C57BL/6J carrier mice, either spleen cell-associated or free in the circulation, which would block the activity of cytotoxic T-lymphocytes against LCM virus-infected syngeneic target cells. The results indicate that inability of LCM virus carrier mice to act immunologically against virus-infected target cells is due to deletion or irreversible inactivation of T lymphocytes carrying receptors for virally altered cell membrane antigens. (author)

  9. Characterization and specificity of probiotics to prevent salmonella infection in mice

    Directory of Open Access Journals (Sweden)

    Ana Andino

    2014-08-01

    Full Text Available Background: Probiotic strains of bacteria can prevent Salmonella from causing disease by preventing the pathogen from colonizing the intestines. Two strains of probiotics, Lactobacillus acidophilius and Pediococcus spp, that were obtained from poultry fecal samples have been shown to be efficacious in poultry. The objective of this study was to determine if these strains of probiotics could prevent salmonellosis in a mouse model. Methods: First, both strains of probiotics were evaluated for in vitro efficacy to inhibit the growth of and interfere with virulence gene regulation in Salmonella enterica. For in vivo efficacy, mice was used which models Typhoid illness. Mice were divided into 2 groups: Control and treatment, Lactobacillus and Pediococcus (LP; 108 Log CFU. Two experiments were conducted. In the first experiment, the mice were treated with LP in water for the first two days of the experiment and challenged with Salmonella at day three. In the second experiment, the LP treatment was given in the water for 10 days and challenge was performed on day 11. In both experiments, at day 20 post-challenge, all mice were sacrificed, intestinal tracts and organs removed and cultured for Salmonella. Results: The probiotic strains inhibited the growth of Salmonella and down-regulation of virulence genes was noted, but dependent on the strain of Salmonella being evaluated. For the in vivo experiment, the probiotics did not afford the mice protection from infection and increasing the length of time the probiotics were administered did not improve the efficacy of the probiotics. Conclusions: It appears that these strains of probiotic bacteria are effective against Salmonella in vitro. However, these isolates did not afford protection from Salmonella infection to mice which may be due to host specifity as these isolates were obtained from poultry

  10. Mortality in patients with chronic and cleared hepatitis C viral infection: a nationwide cohort study

    DEFF Research Database (Denmark)

    Omland, Lars Haukali; Krarup, Henrik; Jepsen, Peter

    2010-01-01

    It is unknown whether mortality differs between patients with chronic hepatitis C virus (HCV) replication and those who cleared the virus after infection. We examined the impact of chronic HCV replication on mortality among Danish patients testing positive for HCV antibodies.......It is unknown whether mortality differs between patients with chronic hepatitis C virus (HCV) replication and those who cleared the virus after infection. We examined the impact of chronic HCV replication on mortality among Danish patients testing positive for HCV antibodies....

  11. Rate of red blood cell destruction varies in different strains of mice infected with Plasmodium berghei-ANKA after chronic exposure

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    Kikuchi Mihoko

    2009-05-01

    Full Text Available Abstract Background Severe malaria anaemia in the semi-immune individuals in the holo-endemic area has been observed to occur at low parasite density with individual variation in the responses. Thus the following has been thought to be involved: auto-immune-mediated mechanisms of uninfected red blood cell destruction, and host genetic factors to explain the differences in individual responses under the same malaria transmission. In this study, the extent of red blood cell (RBC destruction in different strains of semi-immune mice model at relatively low parasitaemia was studied. Methodology To generate semi-immunity, four strains of mice were taken through several cycles of infection and treatment. By means of immunofluorescent assay and ELISA, sera were screened for anti-erythrocyte auto-antibodies, and their relationship with haematological parameters and parasitaemia in the strains of semi-immune mice was investigated. Results Upon challenge with Plasmodium berghei ANKA after generating semi-immune status, different mean percentage haemoglobin (Hb drop was observed in the mice strains (Balb/c = 47.1%; NZW = 30.05%; C57BL/6 = 28.44%; CBA = 25.1%, which occurred on different days for each strain (for Balb/c, mean period = 13.6 days; for C57BL/6, NZW, and CBA mean period = 10.6, 10.8, 10.9 days respectively. Binding of antibody to white ghost RBCs was observed in sera of the four strains of semi-immune mice by immunofluorescence. Mean percentage Hb drop per parasitaemia was highest in Balb/c (73.6, followed by C57BL/6 (8.6, CBA (6.9 and NZW (4.0, p = 0.0005. Consequently, auto-antibodies level to ghost RBC were correlated with degree of anaemia and were highest in Balb/c, when compared with the other strains, p Conclusion The results presented in this study seem to indicate that anti-RBC auto-antibodies may be involved in the destruction of uninfected RBC in semi-immune mice at relatively low parasite burden. Host genetic factors may also

  12. Significance of occult hbv infection in patients with chronic hepatitis c

    International Nuclear Information System (INIS)

    Anwar, W.; Sarwar, M.; Saif, M.; Hussain, A.B.; Tariq, W.Z.

    2006-01-01

    Objective: To determine the frequency of occurrence of occult Hepatitis B infection in chronic hepatitis C patients and its impact (if any) on the effectivity of standard chronic hepatitis C treatment. Design: Quasi-experimental study. Place and Duration of Study: The study was conducted at the Department of Medicine, Military Hospital, Rawalpindi, and Virology Department, Armed Forces Institute of Pathology, Rawalpindi, for a period of nine months from January 2003 to September 2003. Patients and Methods: This study was conducted on 30 HBsAg negative patients with chronic hepatitis C liver disease who were receiving combination therapy with interferon and ribavirin. Occult hepatitis B infection was assessed by carrying out HBV DNA by polymerase chain reaction (PCR) in the sera of these patients. Markers of previous hepatitis B infection Le; anti-HBs and total anti-HBc antibodies were also tested. Response to treatment for hepatitis C (with interferon and ribavirin) was assessed at the end of six months of therapy by measuring ALT levels and HCV RNA by PCR in the serum. Results: In our study only one patient (3.33%) was found to be harbouring HBV DNA in the serum detectable by PCR, with markers of previous HBV infection (both anti HBc antibodies and anti HBs antibodies were positive). A total 14 patients (46.67%) had markers of previous HBV infection, while 16 patients (53.33%) had no such sero markers. Twenty five out of 30 patients (83.33%) responded to treatment and 5 (16.66%) turned out to be non-responders. The single case of occult hepatitis B detected in this study responded to hepatitis C treatment. Conclusion: Occult hepatitis B is not a common occurrence in chronic hepatitis C patients and it did not alter the outcome of treatment for hepatitis C in our study. (author)

  13. The role of environmental tobacco exposure and Helicobacter pylori infection in the risk of chronic tonsillitis in children

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    Chen Li’e

    Full Text Available ABSTRACT CONTEXT AND OBJECTIVE: Helicobacter pylori (H. pylori is a chronic infectious pathogen with high prevalence. This study investigated the interaction between environmental tobacco exposure and H. pylori infection on the incidence of chronic tonsillitis in Chinese children. DESIGN AND SETTING: Cross-sectional study performed in an outpatient clinic in China. METHODS: Pediatric patients with chronic tonsillitis were enrolled. H. pylori infection was determined according to the presence of H. pylori CagA IgG antibodies. Serum cotinine levels and environmental tobacco smoke (ETS exposure were determined for all participants. RESULTS: There was no significant difference in H. pylori infection between the children with chronic tonsillitis and children free of disease, but there was a significant difference in ETS between the two groups (P = 0.011. We next studied the association between ETS and chronic tonsillitis based on H. pylori infection status. In the patients with H. pylori infection, there was a significant difference in ETS distribution between the chronic tonsillitis and control groups (P = 0.022. Taking the participants without ETS as the reference, multivariate logistic regression analysis showed that those with high ETS had higher susceptibility to chronic tonsillitis (adjusted OR = 2.33; 95% CI: 1.67-3.25; adjusted P < 0.001. However, among those without H. pylori infection, ETS did not predispose towards chronic tonsillitis. CONCLUSION: Our findings suggest that tobacco exposure should be a putative mediator risk factor to chronic tonsillitis among children with H. pylori infection.

  14. Using of essential oils in the treatment of mice infected with Trypanosoma evansi

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    Matheus D. Baldissera

    2014-06-01

    Full Text Available Objective. This study aimed to test the effectiveness of copaiba, andiroba and aroeira essential oils for controlling trypanosomosis by Trypanosoma evansi with mice as experimental model. Materials and methods. Sixty-six mice were divided into eleven groups (A to L with six animals each. Group A was the unique composed by healthy and uninfected animals (negative control. Animals in groups B to L were inoculated with 0.1 mL of blood containing 2.7 x 106 trypanosomes. Group B was used as a positive control without treatment. In experiment were tested copaiba (C, D and E, andiroba (F, G and H and aroeira (I, J and L oils at doses of 0.6, 0.8 and 1.0 mL kg-1 to infected mice (T. evansi. Results. These protocols did not provide curative efficacy; however, the mice treated with highest dose of copaiba showed a significant increase in the longevity when compared others groups. Conclusions. Previously in our studies, these essential oils have shown trypanocidal activity in vitro, but when they were tested in vivo in mice infected with T. evansi, this trypanocidal activity, or the curative effect was not found, being only able to prolong the lifespan of the animals treated with copaiba oil.

  15. The Efect of Probiotic Lactobacilli and Alginite on the Cellular Immune Response in Salmonella Infected Mice

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    Hlubeňová K.

    2017-06-01

    Full Text Available Alginite is organic matter rich in humic substances and commonly found in nature, but despite that, the knowledge of its biological effects is limited. In our study we focused on monitoring the effects of alginite alone, as well as its effect as a carrier of probiotic lactobacilli on the cellular immune response in SPF mice after infection with Salmonella Typhimurium. Sixty six conventional SPF female mice of the Balb/c line were divided into 4 groups: 1. infection free negative control (NK supplied neither alginite nor probiotic lactobacilli in the feed; 2. infection free alginite control (Alg supplied feed with 10 % alginite; infected control supplied alginite in the feed but no lactobacilli; 3. infectious control (Alg + Sal - animals infected with salmonella and supplied 10 % alginite in the feed but no lactobacilli;and 4. probiotic group (Lab + Alg + Sal - animals infected with salmonella and administered 10 % alginite and Lactobacillus reuteri 2/6 in the feed. On day 21 of the experiments, the mice were bled and their mesenteric lymph nodes were taken after their death. The peripheral blood of the mice was analysed for the activity of phagocytes and the percentage of selected lymphocyte subpopulations was determined in the mesenteric lymph nodes and blood. The significantly highest phagocytic activity (FA was noted in the infected group with alginite (Alg + Sal. The FA was significantly increased in groups Alg and Lab + Alg + Sal in comparison with the NK group. The highest engulfing ability of phagocytes (phagocytic index was observed in the Lab + Alg + Sal group in comparison with other groups, but also in Alg group in comparison with NK. In the Lab + Alg + Sal group, we observed a significantly higher percentage of B-lymphocytes, CD4+CD8+ and natural killer T cells (NKT, but more significant impact on the numbers of subpopulations of lymphocytes was observed in the mesenteric lymph nodes, with the significantly highest proportions of CD4

  16. Granulocyte colony-stimulating factor protects mice during respiratory virus infections.

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    Tamar Hermesh

    Full Text Available A burst in the production of pro-inflammatory molecules characterizes the beginning of the host response to infection. Cytokines, chemokines, and growth factors work in concert to control pathogen replication and activate innate and adaptive immune responses. Granulocyte colony-stimulating factor (G-CSF mobilizes and activates hematopoietic cells from the bone marrow, and it has been shown to mediate the generation of effective immunity against bacterial and fungal infections. G-CSF is produced at high levels in the lungs during infection with influenza and parainfluenza viruses, but its role during these infections is unknown. Here we show that during infection of mice with a non-lethal dose of influenza or Sendai virus, G-CSF promotes the accumulation of activated Ly6G+ granulocytes that control the extent of the lung pro-inflammatory response. Remarkably, these G-CSF-mediated effects facilitate viral clearance and sustain mouse survival.

  17. The Risk of Chronic Gastrointestinal Disorders Following Acute Infection with Intestinal Parasites

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    Jason Blitz

    2018-01-01

    Full Text Available Background: Infectious gastroenteritis (IGE is caused by numerous bacterial, viral, and parasitic pathogens. A history of IGE has been shown in previous studies to increase the risk of developing chronic gastrointestinal disorders and other chronic conditions. As bacteria and viruses represent the majority of pathogen-specific causes of IGE, post-infectious studies have primarily focused on these organisms. The objective of this study was to investigate an association between a history of parasite-associated IGE and the subsequent development of chronic post-infectious gastrointestinal and non-gastrointestinal disorders in a military population.Methods: International Classification of Diseases, 9th Revision Clinical Modification (ICD-9-CM diagnostic coding data for primary exposures and outcomes were obtained for a retrospective cohort study of active component military personnel from 1998 to 2013. Exposed subjects consisted of individuals with documented infection with one of ten parasitic pathogens. Unexposed subjects were matched to exposed subjects on demographic and operational deployment history parameters. Adjusted odds ratios (aORs were estimated using logistic regression for several chronic disorders previously shown to be associated with a history of IGE.Results: A total of 896 subjects with a parasitic exposure were matched to 3681 unexposed subjects for multivariate regression analysis. Individuals infected with Balantidium coli, Ascaris lumbricoides, Strongyloides stercoralis, Necator americanus/Ancylostoma duodenale, and Taenia spp. had higher aOR for development of several chronic gastrointestinal disorders when compared with unexposed subjects after controlling for various covariates.Conclusion: We found that parasite-associated enteric infection increases the risk of development of post-infectious chronic gastrointestinal disorders in a military population. These results require confirmation in similar populations and in the

  18. Effects of Thymus vulgaris ethanolic extract on chronic toxoplasmosis in a mouse model.

    Science.gov (United States)

    Eraky, Maysa Ahmad; El-Fakahany, Amany Farouk; El-Sayed, Nagwa Mostafa; Abou-Ouf, Eman Abdel-Rahman; Yaseen, Doaa Ibrahim

    2016-07-01

    The current work was undertaken to investigate the potential effectiveness of Thymus vulgaris ethanolic extract (TVE) against Toxoplasma gondii infection in chronic experimental toxoplasmosis. To evaluate prophylactic effects, mice received 500 mg/kg TVE for 5 days before they were infected by an avirulent Me49 T. gondii strain. To investigate the therapeutic effects of the extract postinfection, daily treatment with TVE was initiated at 6 weeks postinfection and continued for 10 days. The following groups of animals were used as controls: uninfected/non-treated, infected/non-treated, and infected/treated with a combination of pyrimethamine and sulfadiazine. Brain cyst count and histopathological changes using H&E and Feulgen stains were used to evaluate the efficacy of TVE. The mean number of brain cysts was significantly decreased by 24 % in mice treated prophylactically with TVE. TVE also significantly reduced the mean number of brain cysts when administered to animals already chronically infected with T. gondii. The effect of TVE was comparable to that of treatment with a mixture of sulfadiazine and pyrimethamine (46 and 51 % reduction, respectively). Moreover, considerable amelioration of the pathological lesions in the brain and retina was observed. The results demonstrate the potential efficacy of T. vulgaris as a new natural therapeutic and prophylactic agent for use in the treatment of chronic toxoplasmosis.

  19. Effect of Porphyromonas gingivalis infection on post-transcriptional regulation of the low-density lipoprotein receptor in mice

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    Miyazawa Haruna

    2012-09-01

    Full Text Available Abstract Background Periodontal disease is suggested to increase the risk of atherothrombotic disease by inducing dyslipidemia. Recently, we demonstrated that proprotein convertase subtilisin/kexin type 9 (PCSK9, which is known to play a critical role in the regulation of circulating low-density lipoprotein (LDL cholesterol levels, is elevated in periodontitis patients. However, the underlying mechanisms of elevation of PCSK9 in periodontitis patients are largely unknown. Here, we explored whether Porphyromonas gingivalis, a representative periodontopathic bacterium, -induced inflammatory response regulates serum PCSK9 and cholesterol levels using animal models. Methods We infected C57BL/6 mice intraperitoneally with Porphyromonas gingivalis, a representative strain of periodontopathic bacteria, and evaluated serum PCSK9 levels and the serum lipid profile. PCSK9 and LDL receptor (LDLR gene and protein expression, as well as liver X receptors (Lxrs, inducible degrader of the LDLR (Idol, and sterol regulatory element binding transcription factor (Srebf2 gene expression, were examined in the liver. Results P. gingivalis infection induced a significant elevation of serum PCSK9 levels and a concomitant elevation of total and LDL cholesterol compared with sham-infected mice. The LDL cholesterol levels were significantly correlated with PCSK9 levels. Expression of the Pcsk9, Ldlr, and Srebf2 genes was upregulated in the livers of the P. gingivalis-infected mice compared with the sham-infected mice. Although Pcsk9 gene expression is known to be positively regulated by sterol regulatory element binding protein (SREBP2 (human homologue of Srebf2, whereas Srebf2 is negatively regulated by cholesterol, the elevated expression of Srebf2 found in the infected mice is thought to be mediated by P. gingivalis infection. Conclusions P. gingivalis infection upregulates PCSK9 production via upregulation of Srebf2, independent of cholesterol levels. Further studies

  20. MRI Visualization of Staphyloccocus aureus-Induced Infective Endocarditis in Mice

    Science.gov (United States)

    Ring, Janine; Hoerr, Verena; Tuchscherr, Lorena; Kuhlmann, Michael T.; Löffler, Bettina; Faber, Cornelius

    2014-01-01

    Infective endocarditis (IE) is a severe and often fatal disease, lacking a fast and reliable diagnostic procedure. The purpose of this study was to establish a mouse model of Staphylococcus aureus-induced IE and to develop a MRI technology to characterize and diagnose IE. To establish the mouse model of hematogenous IE, aortic valve damage was induced by placing a permanent catheter into right carotid artery. 24 h after surgery, mice were injected intravenously with either iron particle-labeled or unlabeled S. aureus (strain 6850). To distinguish the effect of IE from mere tissue injury or recruited macrophages, subgroups of mice received sham surgery prior to infection (n = 17), received surgery without infection (n = 8), or obtained additionally injection of free iron particles to label macrophages (n = 17). Cardiac MRI was performed 48 h after surgery using a self-gated ultra-short echo time (UTE) sequence (TR/TE, 5/0.31 ms; in-plane/slice, 0.125/1 mm; duration, 12∶08 min) to obtain high-resolution, artifact-free cinematographic images of the valves. After MRI, valves were either homogenized and plated on blood agar plates for determination of bacterial titers, or sectioned and stained for histology. In the animal model, both severity of the disease and mortality increased with bacterial numbers. Infection with 105 S. aureus bacteria reliably caused endocarditis with vegetations on the valves. Cinematographic UTE MRI visualised the aortic valve over the cardiac cycle and allowed for detection of bacterial vegetations, while mere tissue trauma or labeled macrophages were not detected. Iron labeling of S. aureus was not required for detection. MRI results were consistent with histology and microbial assessment. These data showed that S. aureus-induced IE in mice can be detected by MRI. The established mouse model allows for investigation of the pathophysiology of IE, testing of novel drugs and may serve for the development of a clinical diagnostic

  1. Interleukin-1 receptor type I gene-deficient mice are less susceptible to Staphylococcus epidermidis biomaterial-associated infection than are wild-type mice

    NARCIS (Netherlands)

    Boelens, J. J.; van der Poll, T.; Zaat, S. A.; Murk, J. L.; Weening, J. J.; Dankert, J.

    2000-01-01

    Elevated concentrations of interleukin-1 (IL-1) were found in tissue surrounding biomaterials infected with Staphylococcus epidermidis. To determine the role of IL-1 in biomaterial-associated infection (BAI), IL-1 receptor type I-deficient (IL-1R(-/-)) and wild-type mice received subcutaneous

  2. Some putative prebiotics increase the severity of Salmonella enterica serovar Typhimurium infection in mice

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    Lahtinen Sampo

    2009-01-01

    Full Text Available Abstract Background Prebiotics are non-digestible food ingredients believed to beneficially affect host health by selectively stimulating the growth of the beneficial bacteria residing in the gut. Such beneficial bacteria have been reported to protect against pathogenic infections. However, contradicting results on prevention of Salmonella infections with prebiotics have been published. The aim of the present study was to examine whether S. Typhimurium SL1344 infection in mice could be prevented by administration of dietary carbohydrates with different structures and digestibility profiles. BALB/c mice were fed a diet containing 10% of either of the following carbohydrates: inulin, fructo-oligosaccharide, xylo-oligosaccharide, galacto-oligosaccharide, apple pectin, polydextrose or beta-glucan for three weeks prior to oral Salmonella challenge (107 CFU and compared to mice fed a cornstarch-based control diet. Results The mice fed with diets containing fructo-oligosaccharide (FOS or xylo-oligosaccharide (XOS had significantly higher (P < 0.01 and P < 0.05 numbers of S. Typhimurium SL1344 in liver, spleen and mesenteric lymph nodes when compared to the mice fed with the cornstarch-based control diet. Significantly increased amounts (P < 0.01 of Salmonella were detected in ileal and fecal contents of mice fed with diets supplemented with apple pectin, however these mice did not show significantly higher numbers of S. Typhimyrium in liver, spleen and lymph nodes than animals from the control group (P < 0.20. The acute-phase protein haptoglobin was a good marker for translocation of S. Typhimurium in mice. In accordance with the increased counts of Salmonella in the organs, serum concentrations of haptoglobin were significantly increased in the mice fed with FOS or XOS (P < 0.001. Caecum weight was increased in the mice fed with FOS (P < 0.01, XOS (P < 0.01, or polydextrose (P < 0.001, and caecal pH was reduced in the mice fed with polydextrose (P < 0

  3. 5′ Rapid Amplification of cDNA Ends and Illumina MiSeq Reveals B Cell Receptor Features in Healthy Adults, Adults With Chronic HIV-1 Infection, Cord Blood, and Humanized Mice

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    Eric Waltari

    2018-03-01

    Full Text Available Using 5′ rapid amplification of cDNA ends, Illumina MiSeq, and basic flow cytometry, we systematically analyzed the expressed B cell receptor (BCR repertoire in 14 healthy adult PBMCs, 5 HIV-1+ adult PBMCs, 5 cord blood samples, and 3 HIS-CD4/B mice, examining the full-length variable region of μ, γ, α, κ, and λ chains for V-gene usage, somatic hypermutation (SHM, and CDR3 length. Adding to the known repertoire of healthy adults, Illumina MiSeq consistently detected small fractions of reads with high mutation frequencies including hypermutated μ reads, and reads with long CDR3s. Additionally, the less studied IgA repertoire displayed similar characteristics to that of IgG. Compared to healthy adults, the five HIV-1 chronically infected adults displayed elevated mutation frequencies for all μ, γ, α, κ, and λ chains examined and slightly longer CDR3 lengths for γ, α, and λ. To evaluate the reconstituted human BCR sequences in a humanized mouse model, we analyzed cord blood and HIS-CD4/B mice, which all lacked the typical SHM seen in the adult reference. Furthermore, MiSeq revealed identical unmutated IgM sequences derived from separate cell aliquots, thus for the first time demonstrating rare clonal members of unmutated IgM B cells by sequencing.

  4. Monoassociation with probiotic Lactobacillus delbrueckii UFV-H2b20 stimulates the immune system and protects germfree mice against Listeria monocytogenes infection.

    Science.gov (United States)

    dos Santos, Liliane Martins; Santos, Mônica Morais; de Souza Silva, Humberto Pereira; Arantes, Rosa Maria Esteves; Nicoli, Jacques Robert; Vieira, Leda Quercia

    2011-02-01

    In the present study, we investigated the protective effects of Lactobacillus delbrueckii UFV-H2b20 on the resistance to Listeria monocytogenes infection in gnotobiotic mice. Germfree mice or monoassociated mice were infected with L. monocytogenes, and the microbiological and immunological responses were evaluated after 1, 3, and 5 days of infection. Monoassociation with L. delbrueckii was capable of protecting mice against death caused by L. monocytogenes and induced a faster clearance of the bacteria in the liver, spleen, and peritoneal cavity at days 1, 3, and 5 post-infection. Also, monoassociated mice displayed less liver injury than germfree mice. The production of TNF-α in the serum, peritoneal cavity, and gut was augmented in monoassociated mice. Likewise, the levels of IFN-γ found on supernatants of spleen cells cultures were higher after the monoassociation. In addition, increased production of nitric oxide in peritoneal cell cultures supernatants and in serum was observed in mice that received L. delbrueckii. The monoassociation with L. delbrueckii induced higher production of IL-10 in the mucosal immune system. We conclude that monoassociation with L. delbrueckii UFV-H2b20 protects mice from death caused by L. monocytogenes infection by favoring effector responses while preventing their immunopathological consequences.

  5. Prevention of Diet-Induced Obesity Effects on Body Weight and Gut Microbiota in Mice Treated Chronically with Δ9-Tetrahydrocannabinol

    Science.gov (United States)

    Cluny, Nina L.; Keenan, Catherine M.; Reimer, Raylene A.; Le Foll, Bernard; Sharkey, Keith A.

    2015-01-01

    Objective Acute administration of cannabinoid CB1 receptor agonists, or the ingestion of cannabis, induces short-term hyperphagia. However, the incidence of obesity is lower in frequent cannabis users compared to non-users. Gut microbiota affects host metabolism and altered microbial profiles are observed in obese states. Gut microbiota modifies adipogenesis through actions on the endocannabinoid system. This study investigated the effect of chronic THC administration on body weight and gut microbiota in diet-induced obese (DIO) and lean mice. Methods Adult male DIO and lean mice were treated daily with vehicle or THC (2mg/kg for 3 weeks and 4 mg/kg for 1 additional week). Body weight, fat mass, energy intake, locomotor activity, whole gut transit and gut microbiota were measured longitudinally. Results THC reduced weight gain, fat mass gain and energy intake in DIO but not lean mice. DIO-induced changes in select gut microbiota were prevented in mice chronically administered THC. THC had no effect on locomotor activity or whole gut transit in either lean or DIO mice. Conclusions Chronic THC treatment reduced energy intake and prevented high fat diet-induced increases in body weight and adiposity; effects that were unlikely to be a result of sedation or altered gastrointestinal transit. Changes in gut microbiota potentially contribute to chronic THC-induced actions on body weight in obesity. PMID:26633823

  6. Role of Transient Receptor Potential Vanilloid 1 in Electroacupuncture Analgesia on Chronic Inflammatory Pain in Mice

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    Jun Yang

    2017-01-01

    Full Text Available Chronic inflammatory pain may result from peripheral tissue injury or inflammation, increasing the release of protons, histamines, adenosine triphosphate, and several proinflammatory cytokines and chemokines. Transient receptor potential vanilloid 1 (TRPV1 is known to be involved in acute to subacute neuropathic and inflammatory pain; however, its exact mechanisms in chronic inflammatory pain are not elucidated. Our results showed that EA significantly reduced chronic mechanical and thermal hyperalgesia in the chronic inflammatory pain model. Chronic mechanical and thermal hyperalgesia were also abolished in TRPV1−/− mice. TRPV1 increased in the dorsal root ganglion (DRG and spinal cord (SC at 3 weeks after CFA injection. The expression levels of downstream molecules such as pPKA, pPI3K, and pPKC increased, as did those of pERK, pp38, and pJNK. Transcription factors (pCREB and pNFκB and nociceptive ion channels (Nav1.7 and Nav1.8 were involved in this process. Inflammatory mediators such as GFAP, S100B, and RAGE were also involved. The expression levels of these molecules were reduced in EA and TRPV1−/− mice but not in the sham EA group. Our data provided evidence to support the clinical use of EA for treating chronic inflammatory pain.

  7. Establishment of Chronic Infection: Brucella's Stealth Strategy

    Science.gov (United States)

    Ahmed, Waqas; Zheng, Ke; Liu, Zheng-Fei

    2016-01-01

    Brucella is a facultative intracellular pathogen that causes zoonotic infection known as brucellosis which results in abortion and infertility in natural host. Humans, especially in low income countries, can acquire infection by direct contact with infected animal or by consumption of animal products and show high morbidity, severe economic losses and public health problems. However for survival, host cells develop complex immune mechanisms to defeat and battle against attacking pathogens and maintain a balance between host resistance and Brucella virulence. On the other hand as a successful intracellular pathogen, Brucella has evolved multiple strategies to evade immune response mechanisms to establish persistent infection and replication within host. In this review, we mainly summarize the “Stealth” strategies employed by Brucella to modulate innate and the adaptive immune systems, autophagy, apoptosis and possible role of small noncoding RNA in the establishment of chronic infection. The purpose of this review is to give an overview for recent understanding how this pathogen evades immune response mechanisms of host, which will facilitate to understanding the pathogenesis of brucellosis and the development of novel, more effective therapeutic approaches to treat brucellosis. PMID:27014640

  8. Garlic blocks quorum sensing and promotes rapid clearing of pulmonary Pseudomonas aeruginosa infections

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Jensen, P. Ø.; Rasmussen, Thomas Bovbjerg

    2005-01-01

    The opportunistic human pathogen Pseudomonas aeruginosa is the predominant micro-organism of chronic lung infections in cystic fibrosis patients. P. aeruginosa colonizes the lungs by forming biofilm microcolonies throughout the lung. Quorum sensing (QS) renders the biofilm bacteria highly tolerant......-treated biofilm. Garlic extract was administered as treatment for a mouse pulmonary infection model. Mice were treated with garlic extract or placebo for 7 days, with the initial 2 days being prophylactic before P. aeruginosa was instilled in the left lung of the mice. Bacteriology, mortality, histopathology...... and phagocytosis by PMNs, as well as leading to an improved outcome of pulmonary infections....

  9. Galectins expressed differently in genetically susceptible C57BL/6 and resistant BALB/c mice during acute ocular Toxoplasma gondii infection.

    Science.gov (United States)

    Chen, S-J; Zhang, Y-X; Huang, S-G; Lu, F-L

    2017-07-01

    Ocular toxoplasmosis (OT) caused by Toxoplasma gondii is a major cause of infectious uveitis, however little is known about its immunopathological mechanism. Susceptible C57BL/6 (B6) and resistant BALB/c mice were intravitreally infected with 500 tachyzoites of the RH strain of T. gondii. B6 mice showed more severe ocular pathology and higher parasite loads in the eyes. The levels of galectin (Gal)-9 and its receptors (Tim-3 and CD137), interferon (IFN)-γ, IL-6 and IL-10 were significantly higher in the eyes of B6 mice than those of BALB/c mice; however, the levels of IFN-α and -β were significantly decreased in the eyes and CLNs of B6 mice but significantly increased in BALB/c mice after infection. After blockage of galectin-receptor interactions by α-lactose, neither ocular immunopathology nor parasite loads were different from those of infected BALB/c mice without α-lactose treatment. Although the expressions of Gal-9/receptor were significantly increased in B6 mice and Gal-1 and -3 were upregulated in both strains of mice upon ocular T. gondii infection, blockage of galectins did not change the ocular pathogenesis of genetic resistant BALB/c mice. However, IFN-α and -β were differently expressed in B6 and BALB/c mice, suggesting that type I IFNs may play a protective role in experimental OT.

  10. A recombinant bivalent fusion protein rVE confers active and passive protection against Yersinia enterocolitica infection in mice.

    Science.gov (United States)

    Singh, Amit Kumar; Kingston, Joseph Jeyabalaji; Murali, Harishchandra Sripathy; Batra, Harsh Vardhan

    2014-03-05

    In the present study, a bivalent chimeric protein rVE comprising immunologically active domains of Yersinia pestis LcrV and YopE was assessed for its prophylactic abilities against Yersinia enterocolitica O:8 infection in murine model. Mice immunized with rVE elicited significantly higher antibody titers with substantial contribution from the rV component (3:1 ratio). Robust and significant resistance to Y. enterocolitica infection with 100% survival (Penterocolitica O:8 against the 75%, 60% and 75% survival seen in mice immunized with rV, rE, rV+rE, respectively. Macrophage monolayer supplemented with anti-rVE polysera illustrated efficient protection (89.41% survival) against challenge of Y. enterocolitica O:8. In contrast to sera from sham-immunized mice, immunization with anti-rVE polysera provided complete protection to BALB/c mice against I.P. challenge with 10(8)CFU of Y. enterocolitica O:8 and developed no conspicuous signs of infection in necropsy. The histopathological analysis of microtome sections confirmed significantly reduced lesion size or no lesion in liver and intestine upon infection in anti-rVE immunized mice. The findings from this study demonstrated the fusion protein rVE as a potential candidate subunit vaccine and showed the functional role of antibodies in protection against Y. enterocolitica infections. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. M2 Macrophages Play Critical Roles in Progression of Inflammatory Liver Disease in Hepatitis C Virus Transgenic Mice.

    Science.gov (United States)

    Ohtsuki, Takahiro; Kimura, Kiminori; Tokunaga, Yuko; Tsukiyama-Kohara, Kyoko; Tateno, Chise; Hayashi, Yukiko; Hishima, Tsunekazu; Kohara, Michinori

    2016-01-01

    Macrophages in liver tissue are widely defined as important inflammatory cells in chronic viral hepatitis due to their proinflammatory activity. We reported previously that interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) play significant roles in causing chronic hepatitis in hepatitis C virus (HCV) transgenic mice (S. Sekiguchi et al., PLoS One 7:e51656, 2012, http://dx.doi.org/10.1371/journal.pone.0051656). In addition, we showed that recombinant vaccinia viruses expressing an HCV nonstructural protein (rVV-N25) could protect against the progression of chronic hepatitis by suppression of macrophage activation. Here, we focus on the role of macrophages in liver disease progression in HCV transgenic mice and examine characteristic features of macrophages following rVV-N25 treatment. The number of CD11b(+) F4/80(+) CD11c(-) CD206(+) (M2) macrophages in the liver of HCV transgenic mice was notably increased compared to that of age-matched control mice. These M2 macrophages in the liver produced elevated levels of IL-6 and TNF-α. rVV-N25 infection suppressed the number and activation of M2 macrophages in liver tissue. These results suggested that inflammatory cytokines produced by M2-like macrophages contribute to the induction of chronic liver inflammation in HCV transgenic mice. Moreover, the therapeutic effect of rVV-N25 might be induced by the suppression of the number and activation of hepatic macrophages. HCV causes persistent infections that can lead to chronic liver diseases, liver fibrosis, and hepatocellular carcinoma; the search for an HCV curative is the focus of ongoing research. Recently, effective anti-HCV drugs have been developed; however, vaccine development still is required for the prevention and therapy of infection by this virus. We demonstrate here that M2 macrophages are important for the pathogenesis of HCV-caused liver diseases and additionally show that M2 macrophages contribute to the therapeutic mechanism observed following r

  12. Serum antibody responses by male and female C57Bl/6 mice infected with Giardia muris.

    Science.gov (United States)

    Daniels, C W; Belosevic, M

    1994-09-01

    We compared the levels of serum antibodies in male and female C57Bl/6 mice during the primary and after challenge infection with Giardia muris. Male mice began passing cysts in their faeces earlier than females, and were shedding cysts for over 60 days, while females stopped shedding cysts by day 20 after infection. In both males and females there were significant increases in parasite-specific IgM 10 and 20 days after infection. No differences in parasite-specific serum IgA were observed until 40 days after infection. Parasite-specific IgG (whole) levels were elevated on days 20 and 40 in females, while males showed no significant increases. In addition, females had a much stronger IgG2b and IgG3 response than males. After challenge with either cysts or soluble parasite protein only the females had significant increases in specific anti-parasite IgG2b. Our data show differential ability of males and females to control the infection with G. muris is paralleled by a difference in the anti-parasite serum IgG response of the mice.

  13. Thymidine Kinase-Negative Herpes Simplex Virus 1 Can Efficiently Establish Persistent Infection in Neural Tissues of Nude Mice.

    Science.gov (United States)

    Huang, Chih-Yu; Yao, Hui-Wen; Wang, Li-Chiu; Shen, Fang-Hsiu; Hsu, Sheng-Min; Chen, Shun-Hua

    2017-02-15

    Herpes simplex virus 1 (HSV-1) establishes latency in neural tissues of immunocompetent mice but persists in both peripheral and neural tissues of lymphocyte-deficient mice. Thymidine kinase (TK) is believed to be essential for HSV-1 to persist in neural tissues of immunocompromised mice, because infectious virus of a mutant with defects in both TK and UL24 is detected only in peripheral tissues, but not in neural tissues, of severe combined immunodeficiency mice (T. Valyi-Nagy, R. M. Gesser, B. Raengsakulrach, S. L. Deshmane, B. P. Randazzo, A. J. Dillner, and N. W. Fraser, Virology 199:484-490, 1994, https://doi.org/10.1006/viro.1994.1150). Here we find infiltration of CD4 and CD8 T cells in peripheral and neural tissues of mice infected with a TK-negative mutant. We therefore investigated the significance of viral TK and host T cells for HSV-1 to persist in neural tissues using three genetically engineered mutants with defects in only TK or in both TK and UL24 and two strains of nude mice. Surprisingly, all three mutants establish persistent infection in up to 100% of brain stems and 93% of trigeminal ganglia of adult nude mice at 28 days postinfection, as measured by the recovery of infectious virus. Thus, in mouse neural tissues, host T cells block persistent HSV-1 infection, and viral TK is dispensable for the virus to establish persistent infection. Furthermore, we found 30- to 200-fold more virus in neural tissues than in the eye and detected glycoprotein C, a true late viral antigen, in brainstem neurons of nude mice persistently infected with the TK-negative mutant, suggesting that adult mouse neurons can support the replication of TK-negative HSV-1. Acyclovir is used to treat herpes simplex virus 1 (HSV-1)-infected immunocompromised patients, but treatment is hindered by the emergence of drug-resistant viruses, mostly those with mutations in viral thymidine kinase (TK), which activates acyclovir. TK mutants are detected in brains of immunocompromised

  14. Sub-chronic lung inflammation after airway exposures to Bacillus thuringiensis biopesticides in mice

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    Barfod Kenneth K

    2010-09-01

    exposures to commercial Bt based biopesticides can induce sub-chronic lung inflammation in mice, which may be the first step in the development of chronic lung diseases. Inhalation of Bt aerosols does not induce airway irritation, which could explain why workers may be less inclined to use a filter mask during the application process, and are thereby less protected from exposure to Bt spores.

  15. Therapy of infections in mice irradiated in mixed neutron/photon fields and inflicted with wound trauma: a review of current work.

    Science.gov (United States)

    Ledney, G D; Madonna, G S; Elliott, T B; Moore, M M; Jackson, W E

    1991-10-01

    When host antimicrobial defenses are severely compromised by radiation or trauma in conjunction with radiation, death from sepsis results. To evaluate therapies for sepsis in radiation casualties, we developed models of acquired and induced bacterial infections in irradiated and irradiated-wounded mice. Animals were exposed to either a mixed radiation field of equal proportions of neutrons and gamma rays (n/gamma = 1) from a TRIGA reactor or pure gamma rays from 60[Co sources. Skin wounds (15% of total body surface area) were inflicted under methoxyflurane anesthesia 1 h after irradiation. In all mice, wounding after irradiation decreased resistance to infection. Treatments with the immunomodulator synthetic trehalose dicorynomycolate (S-TDCM) before or after mixed neutron-gamma irradiation or gamma irradiation increased survival. Therapy with S-TDCM for mice irradiated with either a mixed field or gamma rays increased resistance to Klebsiella pneumoniae-induced infections. Combined therapy with S-TDCM and ceftriaxone for K. pneumoniae infections in mice exposed to a mixed radiation field or to gamma rays was more effective than single-agent therapy. In all irradiated-wounded mice, single therapy of acquired infections with an antibiotic or S-TDCM did not increase survival. Survival of irradiated-wounded mice after topical application of gentamicin sulfate cream suggested that bacteria colonizing the wound disseminated systemically in untreated irradiated mice, resulting in death from sepsis. In lethal models of acquired infections in irradiated-wounded mice, significant increases in survival were achieved when systemic treatments with S-TDCM or gentamicin were combined with topical treatments of gentamicin cream. Therapies for sepsis in all mice exposed to a mixed field were less effective than in mice exposed to gamma rays. Nonetheless, the data show a principle by which successful therapy may be provided to individuals receiving tissue trauma in conjunction with

  16. [Experimental model of activated Lamblia (Giardia) muris infection in albino mice].

    Science.gov (United States)

    Irikov, O A; Kovalenko, F P

    2007-01-01

    Experimental L. muris infection was reproduced in 100% of the intact albino mice intragastrically given levomycin in an average total dose of 15.88-34.84 or 0.88-1.02 g/kg for 18-34 days. With levomycin administration, the intensity of giardiasis was 1121.6-8540.1 (mean 4830.9) thousand L. muris trophozoites per animal. The total number of trophozoites per animal decreased to 302.2-3481.4 (mean 1546.4) thousand and 28.1-324.0 (mean 109.4) thousand specimens 5-8 and 11-13 days after discontinuation of the antibiotic, respectively. The maximum number of L. muris trophozoites was observed in the proximal and middle portions of the murine small intestine during and after the administration oflevomycin. The highest isolation of cysts was seen 12-14 days after the initiation of administration of the antibiotic. Following 8-10 days of terminations of a course of levomycin therapy the native smear of animal feces showed no Lamblia cysts. In mice with activated infection, the isolation rate of Lamblia cysts was directly related to the intensity of intestinal infection with trophozoites of the parasite.

  17. Insulin resistance and liver steatosis in chronic hepatitis C infection genotype 3.

    Science.gov (United States)

    Abenavoli, Ludovico; Masarone, Mario; Peta, Valentina; Milic, Natasa; Kobyliak, Nazarii; Rouabhia, Samir; Persico, Marcello

    2014-11-07

    Hepatitis C virus (HCV) infection is a common chronic liver disease worldwide. Non-alcoholic fatty liver disease and insulin resistance (IR) are the major determinants of fibrosis progression and response to antiviral therapy. The pathogenetic link between IR and chronic HCV infection is complex, and is associated with HCV genotype. Liver steatosis is the most common in the patients infected with genotype 3 virus, possibly due to direct effects of genotype 3 viral proteins. To the contrary, hepatic steatosis in the patients infected with other genotypes is thought to be mostly due to the changes in host metabolism, involving IR. In HCV genotype 3, liver steatosis correlates with viral load, reverts after reaching the sustained virologic response and reoccurs in the relapsers. A therapeutic strategy to improve IR and liver steatosis and subsequently the response to antiviral treatment in these patients is warranted.

  18. IL-17 receptor A signaling is protective in infection-stimulated periapical bone destruction.

    Science.gov (United States)

    AlShwaimi, Emad; Berggreen, Ellen; Furusho, Hisako; Rossall, Jonathan Caleb; Dobeck, Justine; Yoganathan, Subbiah; Stashenko, Philip; Sasaki, Hajime

    2013-08-15

    IL-17 is a pleiotropic cytokine produced by Th17 T cells that induces a myriad of proinflammatory mediators. However, different models of inflammation report opposite functional roles of IL-17 signal in terms of its effects on bone destruction. In this study we determined the role of IL-17RA signal in bone resorption stimulated by dentoalveolar infections. Infrabony resorptive lesions were induced by surgical pulp exposure and microbial infection of mouse molar teeth. IL-17 was strongly induced in periapical tissues in wild-type (WT) mice by 7 d after the infection but was not expressed in uninfected mice. Dentoalveolar infections of IL-17RA knockout (KO) mice demonstrated significantly increased bone destruction and more abscess formation in the apical area compared with WT mice. Infected IL-17RA KO mice exhibited significantly increased neutrophils and macrophages compared with the WT littermates at day 21, suggesting a failure of transition from acute to chronic inflammation in the IL-17RA KO mice. The expression of IL-1 (both α and β isoforms) and MIP2 were significantly upregulated in the IL-17RA KO compared with WT mice at day 21 postinfection. The development of periapical lesions in IL-17RA KO mice was significantly attenuated by neutralization of IL-1β and MIP2. Taken together, these results demonstrate that IL-17RA signal seems to be protective against infection-induced periapical inflammation and bone destruction via suppression of neutrophil and mononuclear inflammation.

  19. Vacuolating encephalitis in mice infected by human coronavirus OC43

    International Nuclear Information System (INIS)

    Jacomy, Helene; Talbot, Pierre J.

    2003-01-01

    Involvement of viruses in human neurodegenerative diseases and the underlying pathologic mechanisms remain generally unclear. Human respiratory coronaviruses (HCoV) can infect neural cells, persist in human brain, and activate myelin-reactive T cells. As a means of understanding the human infection, we characterized in vivo the neurotropic and neuroinvasive properties of HCoV-OC43 through the development of an experimental animal model. Virus inoculation of 21-day postnatal C57BL/6 and BALB/c mice led to a generalized infection of the whole CNS, demonstrating HCoV-OC43 neuroinvasiveness and neurovirulence. This acute infection targeted neurons, which underwent vacuolation and degeneration while infected regions presented strong microglial reactivity and inflammatory reactions. Damage to the CNS was not immunologically mediated and microglial reactivity was instead a consequence of direct virus-mediated neuronal injury. Although this acute encephalitis appears generally similar to that induced by murine coronaviruses, an important difference rests in the prominent spongiform-like degeneration that could trigger neuropathology in surviving animals

  20. Chronic cutaneous ulcers secondary to Haemophilus ducreyi infection.

    Science.gov (United States)

    Peel, Trisha N; Bhatti, Deepak; De Boer, Jim C; Stratov, Ivan; Spelman, Denis W

    2010-03-15

    Haemophilus ducreyi is a well recognised causative agent of genital ulcers and chancroid. We report two unusual cases of non-sexually transmitted H. ducreyi infection leading to chronic lower limb ulcers. Both patients were Australian expatriates visiting Australia from the Pacific Islands--one from Papua New Guinea and the other from Vanuatu.

  1. Relation between Helicobacter pylori infection and chronic urticaria

    Directory of Open Access Journals (Sweden)

    Adianez Sugrañes-Montalván

    2017-12-01

    Conclusions: In the present study, the relationship between chronic urticaria and Helicobacter pylori infection was demonstrated. Apparently, the eradicating treatment for Helicobacter pylori was effective as the patients had no symptoms after treatment. Specific immunoglobulin G and Urease Test together constitute a suitable diagnostic module for the diagnosis of Helicobacter pylori conditions.

  2. Chronic exposure to microcystin-LR affected mitochondrial DNA maintenance and caused pathological changes of lung tissue in mice

    International Nuclear Information System (INIS)

    Li, Xinxiu; Xu, Lizhi; Zhou, Wei; Zhao, Qingya; Wang, Yaping

    2016-01-01

    Microcystin-LR (MC-LR), an important variant of cyanotoxin family, was frequently encountered in the contaminated aquatic environment and taken as a potent hepatotoxin. However, a little was known on the association between the long-term MC-LR exposure and lung damage. In this study, we investigated the changes of the pulmonary histopathology, mitochondrial DNA (mtDNA) integrity and the expression of mtDNA encoded genes in the mice with chronic exposed to MC-LR at different concentrations (1, 5, 10, 20 and 40 μg/L) for 12 months. Our results showed that the long-term and persistent exposure to MC-LR disturbed the balance of redox system, influenced mtDNA stability, changed the expression of mitochondrial genes in the lung cells. Notably, MC-LR exposure influenced the level of inflammatory cytokines and resulted in thickening of the alveolar septa. In conclusion, chronic exposure to MC-LR affected mtDNA maintenance, and caused lung impairment in mice. - Highlights: • A simulated natural exposure to MC-LR caused the lung pathological changes. • The chronic exposure disturbed the redox system balance of lung tissue cells. • The chronic exposure impaired the mtDNA stability and mitochondria function. • The lung was one of the vulnerable organs to MC-LR exposure in mice. - Long-term exposure to MC-LR in drinking water disturbed the balance of redox system, affected mitochondrial DNA maintenance and caused lung impairment in mice.

  3. Effects of acute and chronic administration of neurosteroid dehydroepiandrosterone sulfate on neuronal excitability in mice

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    Svob Strac D

    2016-03-01

    Full Text Available Dubravka Svob Strac,1 Josipa Vlainic,1 Janko Samardzic,2 Julija Erhardt,3 Zeljka Krsnik41Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia; 2Institute of Pharmacology, Clinical Pharmacology and Toxicology, Medical Faculty, University of Belgrade, Belgrade, Serbia; 3Department of Animal Physiology, Faculty of Science, University of Zagreb, 4Croatian Institute for Brain Research, Department of Neuroscience, School of Medicine, University of Zagreb, Zagreb, CroatiaBackground: Neurosteroid dehydroepiandrosterone sulfate (DHEAS has been associated with important brain functions, including neuronal survival, memory, and behavior, showing therapeutic potential in various neuropsychiatric and cognitive disorders. However, the antagonistic effects of DHEAS on γ-amino-butyric acidA receptors and its facilitatory action on glutamatergic neurotransmission might lead to enhanced brain excitability and seizures and thus limit DHEAS therapeutic applications. The aim of this study was to investigate possible age and sex differences in the neuronal excitability of the mice following acute and chronic DHEAS administration.Methods: DHEAS was administered intraperitoneally in male and female adult and old mice either acutely or repeatedly once daily for 4 weeks in a 10 mg/kg dose. To investigate the potential proconvulsant properties of DHEAS, we studied the effects of acute and chronic DHEAS treatment on picrotoxin-, pentylentetrazole-, and N-methyl-d-aspartate-induced seizures in mice. The effects of acute and chronic DHEAS administration on the locomotor activity, motor coordination, and body weight of the mice were also studied. We also investigated the effects of DHEAS treatment on [3H]flunitrazepam binding to the mouse brain membranes.Results: DHEAS did not modify the locomotor activity, motor coordination, body weight, and brain [3H]flunitrazepam binding of male and female mice. The results

  4. Syphacia obvelata and Radfordia affinis infection in mice

    DEFF Research Database (Denmark)

    Harslund, Jakob le Fèvre; Mandrupsen, Karina; Bollen, Peter

    Fèvre Harslund, Karina Mandrupsen & Peter Bollen, Biomedical Laboratory, University of Southern Denmark, DK-5000 Odense C, Denmark. Introduction: In 2014 we experienced an infection with pinworms. Subsequent health monitoring revealed positive findings of Radfordia and Tritrichomonas. Activities were...... of IVC have been negative.Treatment strategies for eliminating Tritrichomonas muris have not yet been established, and the protozoa is diagnosed on irregular basis by PCR and microscopy on intestinal smears. Discussion and conclusion: Previously new animals were accepted after evaluation of a recent...... with pinworms and fur mites were successfully treated, and successive health monitoring has demonstrated continuous absence of these pathogens. Tritrichomonas muris is to a wide extent regarded as a commensal in the intestinal lumen with minimal side effects on mice (3), and so far, the infection has not been...

  5. Inhibitory effect of glutathione on oxidative liver injury induced by dengue virus serotype 2 infections in mice.

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    Juan Wang

    Full Text Available The pathogenesis of dengue virus (DV infection has not been completely defined and change of redox status mediated by depletion of glutathione (GSH in host cell is a common result of viral infection. Our previous study has demonstrated that DV serotype 2 (DV2 infection alters host intracellular GSH levels, and exogenous GSH inhibits viral production by modulating the activity of NF-κB in HepG2 cells. GSH is the most powerful intracellular antioxidant and involved in viral infections. Thus, this study was to investigate whether DV2 infection can induce alteration in redox balance and effect of GSH on the disease in HepG2 xenografts SCID mice. Our results revealed that mice infected with DV2 showed alterations in oxidative stress by increasing the level of malondialdehyde (MDA, an end product of lipid peroxidation, and GSSG/GSH ratio. DV2-infected mice also showed a decrease in the activity of catalase (CAT and total superoxide dismutase (T-SOD in the serum and/or observed organs, especially the liver. Moreover, DV2 infection resulted in elevated serum levels of the cytokines tumor necrosis factor-α and interlukin-6 and obvious histopathological changes in the liver. The administration of exogenous GSH significantly reversed all of the aforementioned pathological changes and prevented significant liver damage. Furthermore, in vitro treatment of HepG2 cells with antioxidants such as GSH inhibited viral entry as well as the production of reactive oxygen species in HepG2 cells. These results suggest that GSH prevents DV2-induced oxidative stress and liver injury in mice by inhibiting proinflammatory cytokine production, and GSH and may be a promising therapeutic agent for prevention of oxidative liver damage during DV infection.

  6. Distinct Macrophage Fates after in vitro Infection with Different Species of Leishmania: Induction of Apoptosis by Leishmania (Leishmania) amazonensis, but Not by Leishmania (Viannia) guyanensis.

    Science.gov (United States)

    DaMata, Jarina Pena; Mendes, Bárbara Pinheiro; Maciel-Lima, Kátia; Menezes, Cristiane Alves Silva; Dutra, Walderez Ornelas; Sousa, Lirlândia Pires; Horta, Maria Fátima

    2015-01-01

    Leishmania is an intracellular parasite in vertebrate hosts, including man. During infection, amastigotes replicate inside macrophages and are transmitted to healthy cells, leading to amplification of the infection. Although transfer of amastigotes from infected to healthy cells is a crucial step that may shape the outcome of the infection, it is not fully understood. Here we compare L. amazonensis and L. guyanensis infection in C57BL/6 and BALB/c mice and investigate the fate of macrophages when infected with these species of Leishmania in vitro. As previously shown, infection of mice results in distinct outcomes: L. amazonensis causes a chronic infection in both strains of mice (although milder in C57BL/6), whereas L. guyanensis does not cause them disease. In vitro, infection is persistent in L. amazonensis-infected macrophages whereas L. guyanensis growth is controlled by host cells from both strains of mice. We demonstrate that, in vitro, L. amazonensis induces apoptosis of both C57BL/6 and BALB/c macrophages, characterized by PS exposure, DNA cleavage into nucleosomal size fragments, and consequent hypodiploidy. None of these signs were seen in macrophages infected with L. guyanensis, which seem to die through necrosis, as indicated by increased PI-, but not Annexin V-, positive cells. L. amazonensis-induced macrophage apoptosis was associated to activation of caspases-3, -8 and -9 in both strains of mice. Considering these two species of Leishmania and strains of mice, macrophage apoptosis, induced at the initial moments of infection, correlates with chronic infection, regardless of its severity. We present evidence suggestive that macrophages phagocytize L. amazonensis-infected cells, which has not been verified so far. The ingestion of apoptotic infected macrophages by healthy macrophages could be a way of amastigote spreading, leading to the establishment of infection.

  7. Distinct Macrophage Fates after in vitro Infection with Different Species of Leishmania: Induction of Apoptosis by Leishmania (Leishmania amazonensis, but Not by Leishmania (Viannia guyanensis.

    Directory of Open Access Journals (Sweden)

    Jarina Pena DaMata

    Full Text Available Leishmania is an intracellular parasite in vertebrate hosts, including man. During infection, amastigotes replicate inside macrophages and are transmitted to healthy cells, leading to amplification of the infection. Although transfer of amastigotes from infected to healthy cells is a crucial step that may shape the outcome of the infection, it is not fully understood. Here we compare L. amazonensis and L. guyanensis infection in C57BL/6 and BALB/c mice and investigate the fate of macrophages when infected with these species of Leishmania in vitro. As previously shown, infection of mice results in distinct outcomes: L. amazonensis causes a chronic infection in both strains of mice (although milder in C57BL/6, whereas L. guyanensis does not cause them disease. In vitro, infection is persistent in L. amazonensis-infected macrophages whereas L. guyanensis growth is controlled by host cells from both strains of mice. We demonstrate that, in vitro, L. amazonensis induces apoptosis of both C57BL/6 and BALB/c macrophages, characterized by PS exposure, DNA cleavage into nucleosomal size fragments, and consequent hypodiploidy. None of these signs were seen in macrophages infected with L. guyanensis, which seem to die through necrosis, as indicated by increased PI-, but not Annexin V-, positive cells. L. amazonensis-induced macrophage apoptosis was associated to activation of caspases-3, -8 and -9 in both strains of mice. Considering these two species of Leishmania and strains of mice, macrophage apoptosis, induced at the initial moments of infection, correlates with chronic infection, regardless of its severity. We present evidence suggestive that macrophages phagocytize L. amazonensis-infected cells, which has not been verified so far. The ingestion of apoptotic infected macrophages by healthy macrophages could be a way of amastigote spreading, leading to the establishment of infection.

  8. An immunological analysis of natural resistance to moise hepatitis virus (JHMV strain) infection in C3H mice

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, C A; Pickel, K [Wurzburg Univ. (Germany, F.R.). Inst. fuer Virologie und Immunbiologie

    1987-01-01

    Since the development of resistance against mouse hepatitis virus (JHMV strain) coincides with the maturation of the immune system, we studied the possible role of distinct immunological components in the resistance of adult mice during JHMV infection. Adult C3H mice naturally resistant to JHMV were rendered susceptible to infection by lethal {sup 60}Co-irradiation and were subsequently reconstituted with limiting numbers of syngeneic bone marrow cells or spleen cells. Resistance or susceptibility dependend on the number of cells used for reconstitution and the interval between reconsitution and infection. Spleen cells from suckling mice affected neither resistance nor susceptibility and peritoneal cells from adult mice and thymus cells reduced resistance. Persistence of JHMV was demonstrated by virus reactivation. Animals infected with JHMV only once before being rendered immunoincompetent showed a different pattern of resistance. One to four months after infection, 15 to 35% of the animals died after reconstitution without having been reinfected, and persisting JHMV was found in their liver, spleen and peritoneal exudate. The survivors (47 to 87%) were resistant to further JHMV infection during immunodeficiency. Animals immunized 3 times with JHMV before irradiation did not show virus reactivation and were fully resistant to JHMV reinfection after reconstitution. The level of neutralizing anti JHMV serum antibodies in the group of mice immunized only once was comparable with the level of those immunized 3 times. The role of macrophage activation and cell-mediated immunity in this model are discused as an explanation for the resistance to, and persistence of, JHMV. (author).

  9. An immunological analysis of natural resistance to moise hepatitis virus (JHMV strain) infection in C3H mice

    International Nuclear Information System (INIS)

    Pereira, C.A.; Pickel, K.

    1987-01-01

    Since the development of resistance against mouse hepatitis virus (JHMV strain) coincides with the maturation of the immune system, we studied the possible role of distinct immunological components in the resistance of adult mice during JHMV infection. Adult C3H mice naturally resistant to JHMV were rendered susceptible to infection by lethal 60 Co-irradiation and were subsequently reconstituted with limiting numbers of syngeneic bone marrow cells or spleen cells. Resistance or susceptibility dependend on the number of cells used for reconstitution and the interval between reconsitution and infection. Spleen cells from suckling mice affected neither resistance nor susceptibility and peritoneal cells from adult mice and thymus cells reduced resistance. Persistence of JHMV was demonstrated by virus reactivation. Animals infected with JHMV only once before being rendered immunoincompetent showed a different pattern of resistance. One to four months after infection, 15 to 35% of the animals died after reconstitution without having been reinfected, and persisting JHMV was found in their liver, spleen and peritoneal exudate. The survivors (47 to 87%) were resistant to further JHMV infection during immunodeficiency. Animals immunized 3 times with JHMV before irradiation did not show virus reactivation and were fully resistant to JHMV reinfection after reconstitution. The level of neutralizing anti JHMV serum antibodies in the group of mice immunized only once was comparable with the level of those immunized 3 times. The role of macrophage activation and cell-mediated immunity in this model are discused as an explanation for the resistance to, and persistence of, JHMV. (author) [pt

  10. Morphological studies in a model for dengue-2 virus infection in mice

    Directory of Open Access Journals (Sweden)

    Ortrud Monika Barth

    2006-12-01

    Full Text Available One of the main difficulties in studying dengue virus infection in humans and in developing a vaccine is the absence of a suitable animal model which develops the full spectrum of dengue fever, dengue haemorrhagic fever, and dengue shock syndrome. It is our proposal to present morphological aspects of an animal model which shows many similarities with the dengue infection in humans. BALB/c mice were intraperitoneally infected with non-neuroadapted dengue virus serotype 2 (DENV-2. Histopathological and morphometrical analyses of liver tissue revealed focal alterations along the infection, reaching wide-ranging portal and centrolobular veins congestion and sinusoidal cell death. Additional ultrastructural observations demonstrated multifocal endothelial injury, platelet recruitment, and alterated hepatocytes. Dengue virus antigen was detected in hepatocytes and in the capillar endothelium of the central lobular vein area. Liver function tests showed high levels of aspartate transaminase and alanine transaminase enzyme activity. Lung tissue showed interstitial pneumonia and mononuclear cells, interseptal oedema, hyperplasia, and hypertrophy of the bronchiolar epithelial cells. DENV-2 led to a transient inflammatory process, but caused focal alterations of the blood-exchange barrier. Viremia was observed from 2nd to 11th day p.i. by isolation of DENV-2 in C6/36 mosquito cell line inoculated with the supernatant of macerated liver, lung, kidney, and cerebellum tissues of the infected mice.

  11. Induction of TNF-alfa and CXCL-2 mRNAs in different organs of mice infected with pathogenic Leptospira.

    Science.gov (United States)

    da Silva, Josefa B; Carvalho, Enéas; Covarrubias, Ambart E; Ching, Ana Tung C; Mattaraia, Vania G M; Paiva, Delhi; de Franco, Marcelo; Fávaro, Regiane Degan; Pereira, Martha M; Vasconcellos, Silvio; Zorn, Telma T M; Ho, Paulo Lee; Martins, Elizabeth A L

    2012-04-01

    The role of innate immune response in protection against leptospirosis is poorly understood. We examined the expression of the chemokine CXCL2/MIP-2 and the cytokine TNF-α in experimental resistant and susceptible mice models, C3H/HeJ, C3H/HePas and BALB/c strains, using a virulent strain of Leptospira interrogans serovar Copenhageni. Animals were infected intraperitoneally with 10(7) cells and the development of the disease was followed. Mortality of C3H/HeJ mice was observed whereas C3H/HePas presented jaundice and BALB/c mice remained asymptomatic. The infection was confirmed by the presence of leptospiral DNA in the organs of the animals, demonstrated by PCR. Sections of the organs were analyzed, after H&E stain. The relative expression of mRNA of chemokine CXCL2/MIP-2 and cytokine TNF-α was measured in lung, kidney and liver of the mice by qPCR. The concentrations of these proteins were measured in extracts of tissues and in serum of the animals, by ELISA. Increasing levels of transcripts and protein CXCL2/MIP-2 were detected since the first day of infection. The highest expression was observed at third day of infection in kidney, liver and lung of BALB/c mice. In C3H/HeJ the expression of CXCL2/MIP-2 was delayed, showing highest protein concentration in lung and kidney at the 5th day. Increasing in TNF-α transcripts were detected after infection, in kidney and liver of animals from the three mice strains. The expression of TNF-α protein in C3H/HeJ was also delayed, being detected in kidney and lung. Our data demonstrated that Leptospira infection stimulates early expression of CXCL2/MIP-2 and TNF-α in the resistant strain of mice. Histological analysis suggests that the expression of those molecules may be related to the influx of distinct immune cells and plays a role in the naturally acquired protective immunity. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Coadministration of cruzipain and GM-CSF DNAs, a new immunotherapeutic vaccine against Trypanosoma cruzi infection.

    Science.gov (United States)

    Cerny, Natacha; Sánchez Alberti, Andrés; Bivona, Augusto E; De Marzi, Mauricio C; Frank, Fernanda M; Cazorla, Silvia I; Malchiodi, Emilio L

    2016-01-01

    Therapeutic vaccine research and development are especially important in Chagas disease considering the characteristics of the chronic infection and the number of people in the Americas living with a parasite infection for decades. We have previously reported the efficacy of attenuated Salmonella enterica (S) carrying plasmid encoding cruzipain (SCz) to protect against Trypanosoma cruzi infection. In the present work we investigated whether Cz DNA vaccine immunotherapy could be effective in controlling an ongoing T. cruzi infection in mice. We here report the intramuscular administration of naked Cz DNA or the oral administration of Salmonella as Cz DNA delivery system as therapeutic vaccines in mice during acute or chronic infection. The coadministration of a plasmid encoding GM-CSF improved vaccine performance, indicating that the stimulation of innate immune cells is needed in the event of an ongoing infection. These therapeutic vaccines were able to address the response to a protective and sustained Th1 biased profile not only against Cz but also against a variety of parasite antigens. The combined therapeutic vaccine during the chronic phase of infection prevents tissue pathology as shown by a reduced level of enzyme activity characteristic of tissue damage and a tissue status compatible with normal tissue. The obtained results suggest that immunotherapy with Cz and GM-CSF DNAs, either alone or in combination with other drug treatments, may represent a promising alternative for Chagas disease therapy.

  13. Effect of sucralfate on antibiotic therapy for Helicobacter pylori infection in mice.

    Science.gov (United States)

    Watanabe, Koichiro; Murakami, Kazunari; Sato, Ryugo; Kashimura, Koji; Miura, Masahiro; Ootsu, Satoshi; Miyajima, Hajime; Nasu, Masaru; Okimoto, Tadayoshi; Kodama, Masaaki; Fujioka, Toshio

    2004-12-01

    It has been documented that sucralfate, a basic aluminum salt, enhances the efficacies of antibiotics against Helicobacter pylori, resulting in eradication rates comparable to those associated with the use of proton pump inhibitors. However, its mechanism of action remains unclear. The aim of the present study was to investigate sucralfate's ability to complement antibiotic treatment of H. pylori infection in vivo. Four weeks following induced H. pylori infection, clarithromycin (CAM) and amoxicillin (AMPC) were administered orally to C57BL/6 mice for 5 days, both with and without sucralfate or lansoprazole. When sucralfate was concurrently given with CAM and AMPC at the maximum noninhibitory doses for the treatment of H. pylori infection, the bacterial clearance rates were comparable to those achieved by treatment with lansoprazole plus those antibiotics. The results of pharmacokinetic studies showed that lansoprazole delayed gastric clearance and accelerated the absorption of CAM, whereas sucralfate suppressed both gastric clearance and absorption. AMPC was undetectable in all samples. Scanning electron microscopy with a microscope to which a energy dispersive spectrometer was attached revealed that aluminum-containing aggregated substances coated the mucosa surrounding H. pylori in mice receiving sucralfate plus antibiotics, whereas the gastric surface and pits where H. pylori had attached were clearly visible in mice receiving lansoprazole plus antibiotics. The addition of sucralfate to the antibiotic suspension resulted in a more viscous mixture that bound to the H. pylori-infected mucosa and that inhibited the loss of CAM bioavailability in the acidic environment. Sucralfate delays gastric clearance of CAM and physically captures H. pylori through the creation of an adherent mucus, which leads to bacterial clearance.

  14. Early Life Arsenic Exposure and Acute and Long-term Responses to Influenza A Infection in Mice

    OpenAIRE

    Ramsey, Kathryn A.; Foong, Rachel E.; Sly, Peter D.; Larcombe, Alexander N.; Zosky, Graeme R.

    2013-01-01

    Background: Arsenic is a significant global environmental health problem. Exposure to arsenic in early life has been shown to increase the rate of respiratory infections during infancy, reduce childhood lung function, and increase the rates of bronchiectasis in early adulthood. Objective: We aimed to determine if early life exposure to arsenic exacerbates the response to early life influenza infection in mice. Methods: C57BL/6 mice were exposed to arsenic in utero and throughout postnatal lif...

  15. Prevalence of Irritable Bowel Syndrome and Chronic Fatigue 10 Years After Giardia Infection.

    Science.gov (United States)

    Litleskare, Sverre; Rortveit, Guri; Eide, Geir Egil; Hanevik, Kurt; Langeland, Nina; Wensaas, Knut-Arne

    2018-03-06

    Irritable bowel syndrome (IBS) is a complication that can follow gastrointestinal infection, but it is not clear if patients also develop chronic fatigue. We investigated the prevalence and odds ratio of IBS and chronic fatigue 10 years after an outbreak of Giardia lamblia, compared with a control cohort, and changes in prevalence over time. We performed a prospective follow-up study of 1252 laboratory-confirmed cases of giardiasis (exposed), which developed in Bergen, Norway in 2004. Statistics Norway provided us with information from 2504 unexposed individuals from Bergen, matched by age and sex (controls). Questionnaires were mailed to participants 3, 6, and 10 years after the outbreak. Results from the 3- and 6-year follow-up analyses have been published previously. We report the 10-year data and changes in prevalence among time points, determined by logistic regression using generalized estimating equations. The prevalence of IBS 10 years after the outbreak was 43% (n = 248) among 576 exposed individuals and 14% (n = 94) among 685 controls (adjusted odds ratio for development of IBS in exposed individuals, 4.74; 95% CI, 3.61-6.23). At this time point, the prevalence of chronic fatigue was 26% (n = 153) among 587 exposed individuals and 11% (n = 73) among 692 controls (adjusted odds ratio, 3.01; 95% CI, 2.22-4.08). The prevalence of IBS among exposed persons did not change significantly from 6 years after infection (40%) to 10 years after infection (43%; adjusted odds ratio for the change 1.03; 95% CI, 0.87-1.22). However, the prevalence of chronic fatigue decreased from 31% at 6 years after infection to 26% at 10 years after infection (adjusted odds ratio for the change 0.74; 95% CI, 0.61-0.90). The prevalence of IBS did not change significantly from 6 years after an outbreak of Giardia lamblia infection in Norway to 10 years after. However, the prevalence of chronic fatigue decreased significantly from 6 to 10 years afterward. IBS and chronic fatigue were

  16. Effects of HIV-1 on Cognition in Humanized NSG Mice

    Science.gov (United States)

    Akhter, Sidra Pervez

    Host species specificity of human immunodeficiency virus (HIV) creates a challenge to study the pathology, diagnostic tools, and therapeutic agents. The closely related simian immunodeficiency virus and studies of neurocognitive impairments on transgenic animals expressing partial viral genome have significant limitations. The humanized mice model provides a small animal system in which a human immune system can be engrafted and immunopathobiology of HIV-1 infection can be studied. However, features of HIV-associated neurocognitive disorders (HAND) were not evaluated in this model. Open field activity test was selected to characterize behavior of original strain NOD/scid-IL-2Rgammac null (NSG) mice, effects of engraftment of human CD34+ hematopoietic stem cells (HSCs) and functional human immune system (huNSG), and finally, investigate the behavior changes induced by chronic HIV-1 infection. Long-term infected HuNSG mice showed the loss of working memory and increased anxiety in the open field. Additionally, these animals were utilized for evaluation of central nervous system metabolic and structural changes. Detected behavioral abnormalities are correlated with obtained neuroimaging and histological abnormalities published.

  17. Compromised virus control and augmented perforin-mediated immunopathology in IFN-gamma-deficient mice infected with lymphocytic choriomeningitis virus

    DEFF Research Database (Denmark)

    Nansen, A; Jensen, Teis; Christensen, Jan Pravsgaard

    1999-01-01

    To define the role of IFN-gamma in the control of acute infection with a noncytopathogenic virus, mice with targeted defects of the genes encoding IFN-gamma, perforin, or both were infected i.v. with two strains of lymphocytic choriomeningitis virus differing markedly in their capacity to spread...... in wild-type mice. Our results reveal that IFN-gamma is pivotal to T cell-mediated control of a rapidly invasive stain, whereas it is less important in the acute elimination of a slowly invasive strain. Moreover, the majority of mice infected with the rapidly invasive strain succumb to a wasting syndrome...... mediated by CD8+ effector cells. The primary effector mechanism underlying this disease is perforin-dependent lysis, but other mechanisms are also involved. Wasting disease can be prevented if naive CD8+ cells from mice transgenic for an MHC class I-restricted lymphocytic choriomeningitis virus...

  18. Immunoperoxidase technique in experimental chronic chagasic myocarditis

    Directory of Open Access Journals (Sweden)

    M.d. Maria Celina Morales

    1987-04-01

    Full Text Available Chagas'disease has been described as the commonest form of chronic myocarditis. An immunologic pathogenesis has been discribed for this form of the disease. So far, no immunoperoxidase technique has been used for the detection of immunological deposits in chronic experimental Chagas'myocardiopathy. Forty-one Swiss mice, three months old were inoculated intraperitoneally with doses between 10 and 10(5 Tulahuen trypomastigotes. Mice were reinoculated one month after with doses between 10² and 10(5 and sacrificed at 6 (n=21 and 9 months (n=9 after the first inoculation. ECGs were recorded before sacrifice. Immunoperoxidase technique (peroxidase-antiperoxidase method, immunofluorescence (direct and indirect as well as histological studies were performed in myocardiums and skeletal muscles of the surviving animals. The most sensitive methods for detecting chronic chagasic infection were the routine histologic studies (73% and the ECGs 83% and 89% on 6 and 9 mo. post-infected mice, respectively. Myocardial involvement varied from interstitial mild focal lymphocyte infiltrates up to replacement of myocytes by loose connective tissue. Atrial myocardiums (21/23, 91% were more affected than ventricles (9/23, 39%. Typical chagasic nests were rarely found. Skeletal muscle involvement (11/18 and 7/9 varied from mild to extensive lymphocyte and plasmacell infiltrates, and necrotic fibers. The involved antigen were shown in skeletal muscles by the immunoperoxidase technique as diffusely arranged granular intracytoplasmatic deposit for both IgC and total immunoglobulins. The coincidence between this technique and histologic muscle lesions was 11/18 (61(% in 6 mo. and 6/8 (75% at 9 mo. post-infection. In heart, delicate granular deposits of total immunoglobulins were seen diffusely arranged within the ventricular myocytes; coincidence between immunoperoxidase technique anl histologic involvement increased from 36 to 66% in animals sacrifeced 6 and 9 mo. post-infection

  19. Sequential colonization of periodontal pathogens in induction of periodontal disease and atherosclerosis in LDLRnull mice.

    Science.gov (United States)

    Chukkapalli, Sasanka S; Easwaran, Meena; Rivera-Kweh, Mercedes F; Velsko, Irina M; Ambadapadi, Sriram; Dai, Jiayin; Larjava, Hannu; Lucas, Alexandra R; Kesavalu, Lakshmyya

    2017-01-01

    Periodontal disease (PD) and atherosclerotic vascular disease (ASVD) are both chronic inflammatory diseases with a polymicrobial etiology and have been epidemiologically associated. The purpose is to examine whether periodontal bacteria that infect the periodontium can also infect vascular tissues and enhance pre-existing early aortic atherosclerotic lesions in LDLRnull mice. Mice were orally infected with intermediate bacterial colonizer Fusobacterium nucleatum for the first 12 weeks followed by late bacterial colonizers (Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia) for the remaining 12 weeks mimicking the human oral microbiota ecological colonization. Genomic DNA from all four bacterial was detected in gingival plaque by PCR, consistently demonstrating infection of mouse gingival surfaces. Infected mice had significant levels of IgG and IgM antibodies, alveolar bone resorption, and showed apical migration of junctional epithelium revealing the induction of PD. These results support the ability of oral bacteria to cause PD in mice. Detection of bacterial genomic DNA in systemic organs indicates hematogenous dissemination from the gingival pockets. Bacterial infection did not alter serum lipid fractions or serum amyloid A levels and did not induce aortic atherosclerotic plaque. This is the first study examining the causal role of periodontal bacteria in induction of ASVD in LDLRnull mice. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Estimation of TiO₂ nanoparticle-induced genotoxicity persistence and possible chronic gastritis-induction in mice.

    Science.gov (United States)

    Mohamed, Hanan Ramadan Hamad

    2015-09-01

    Titanium dioxide (TiO2) nanoparticles are widely used as a food additive and coloring agent in many consumer products however limited data is available on the nano-TiO2 induced genotoxicity persistence. Thus, this study investigated the persistence of nano-TiO2 induced genotoxicity and possible induction of chronic gastritis in mice. The mice were orally administered 5, 50 or 500 mg/kg body weight nano-TiO2 for five consecutive days, and then mice from each dosage group were sacrificed 24 h or one or two weeks after the last treatment. The administration of nano-TiO2 resulted in persistent apoptotic DNA fragmentation and mutations in p53 exons (5-8) as well as significant persistent elevations in malondialdehyde and nitric oxide levels and decreases in the reduced glutathione level and catalase activity compared with the control mice in a dose- and time-dependent manner. Necrosis and inflammation were evident upon histological examination. These findings could be attributed to the persistent accumulation of nano-TiO2 at the tested doses at all three time points. Based on these findings, we conclude that the administration of nano-TiO2, even at low doses, leads to persistent accumulation of nano-TiO2 in mice, resulting in persistent inflammation, apoptosis and oxidative stress, ultimately leading to the induction of chronic gastritis. Copyright © 2015 Elsevier Ltd. All rights reserved.