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Sample records for postoperative host immunity

  1. Host genetics affect microbial ecosystems via host immunity.

    Science.gov (United States)

    El Kafsi, Hela; Gorochov, Guy; Larsen, Martin

    2016-10-01

    Genetic evolution of multicellular organisms has occurred in response to environmental challenges, including competition for nutrients, climate change, physical and chemical stressors, and pathogens. However, fitness of an organism is dependent not only on defense efficacy, but also on the ability to take advantage of symbiotic organisms. Indeed, microbes not only encompass pathogenicity, but also enable efficient nutrient uptake from diets nondegradable by the host itself. Moreover, microbes play important roles in the development of host immunity. Here we review associations between specific host genes and variance in microbiota composition and compare with interactions between microbes and host immunity. Recent genome-wide association studies reveal that symbiosis between host and microbiota is the exquisite result of genetic coevolution. Moreover, a subset of microbes from human and mouse microbiota have been identified to interact with humoral and cellular immunity. Interestingly, microbes associated with both host genetics and host immunity are taxonomically related. Most involved are Bifidobacterium, Lactobacillus, and Akkermansia, which are dually associated with both host immunity and host genetics. We conclude that future therapeutics targeting microbiota in the context of chronic inflammatory diseases need to consider both immune and genetic host features associated with microbiota homeostasis.

  2. Epigenetic modulation of host: new insights into immune evasion by ...

    Indian Academy of Sciences (India)

    Viruses have evolved with their hosts, which include all living species. This has been partly responsible for the development of highly advanced immune systems in the hosts. However, viruses too have evolved ways to regulate and evade the host's immune defence. In addition to mutational mechanisms that viruses employ ...

  3. Evasion of host immune defenses by human papillomavirus.

    Science.gov (United States)

    Westrich, Joseph A; Warren, Cody J; Pyeon, Dohun

    2017-03-02

    A majority of human papillomavirus (HPV) infections are asymptomatic and self-resolving in the absence of medical interventions. Various innate and adaptive immune responses, as well as physical barriers, have been implicated in controlling early HPV infections. However, if HPV overcomes these host immune defenses and establishes persistence in basal keratinocytes, it becomes very difficult for the host to eliminate the infection. The HPV oncoproteins E5, E6, and E7 are important in regulating host immune responses. These oncoproteins dysregulate gene expression, protein-protein interactions, posttranslational modifications, and cellular trafficking of critical host immune modulators. In addition to the HPV oncoproteins, sequence variation and dinucleotide depletion in papillomavirus genomes has been suggested as an alternative strategy for evasion of host immune defenses. Since anti-HPV host immune responses are also considered to be important for antitumor immunity, immune dysregulation by HPV during virus persistence may contribute to immune suppression essential for HPV-associated cancer progression. Here, we discuss cellular pathways dysregulated by HPV that allow the virus to evade various host immune defenses. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  4. Immune defense and host life history.

    Science.gov (United States)

    Zuk, Marlene; Stoehr, Andrew M

    2002-10-01

    Recent interest has focused on immune response in an evolutionary context, with particular attention to disease resistance as a life-history trait, subject to trade-offs against other traits such as reproductive effort. Immune defense has several characteristics that complicate this approach, however; for example, because of the risk of autoimmunity, optimal immune defense is not necessarily maximum immune defense. Two important types of cost associated with immunity in the context of life history are resource costs, those related to the allocation of essential but limited resources, such as energy or nutrients, and option costs, those paid not in the currency of resources but in functional or structural components of the organism. Resource and option costs are likely to apply to different aspects of resistance. Recent investigations into possible trade-offs between reproductive effort, particularly sexual displays, and immunity have suggested interesting functional links between the two. Although all organisms balance the costs of immune defense against the requirements of reproduction, this balance works out differently for males than it does for females, creating sex differences in immune response that in turn are related to ecological factors such as the mating system. We conclude that immune response is indeed costly and that future work would do well to include invertebrates, which have sometimes been neglected in studies of the ecology of immune defense.

  5. Modulation of host immunity by tick saliva

    Czech Academy of Sciences Publication Activity Database

    Kotál, Jan; Langhansová, H.; Lieskovská, J.; Andersen, J. F.; Francischetti, I.M.B.; Chavakis, T.; Kopecký, J.; Pedra, J. H. F.; Kotsyfakis, Michalis; Chmelař, J.

    2015-01-01

    Roč. 128, OCT 14 2015 (2015), s. 58-68 ISSN 1874-3919 R&D Projects: GA ČR GAP502/12/2409 Institutional support: RVO:60077344 Keywords : Adaptive immunity * Innate immunity * Saliva * Salivary glands * Tick Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.867, year: 2015

  6. Escaping deleterious immune response in their hosts: lessons from trypanosomatids

    Directory of Open Access Journals (Sweden)

    Anne eGeiger

    2016-05-01

    Full Text Available The Trypanosomatidae family includes the genera Trypanosoma and Leishmania, protozoan parasites displaying complex digenetic life cycles requiring a vertebrate host and an insect vector. Trypanosoma brucei gambiense, T. cruzi and Leishmania spp are important human pathogens causing Human African Trypanosomiasis (HAT or Sleeping Sickness, Chagas’ disease, and various clinical forms of Leishmaniasis, respectively. They are transmitted to humans by tsetse flies, triatomine bugs or sandflies and affect millions of people worldwide.In humans, extracellular African trypanosomes (T. brucei evade the hosts’ immune defences, allowing their transmission to the next host, via the tsetse vector. By contrast, T. cruzi and Leishmania sp. have developed a complex intracellular lifestyle, also preventing several mechanisms to circumvent the host’s immune response.This review seeks to set out the immune evasion strategies developed by the different trypanosomatids resulting from parasite-host interactions and, will focus on: clinical and epidemiological importance of diseases; life cycles: parasites-hosts-vectors; innate immunity: key steps for trypanosomatids in invading hosts; deregulation of antigen presenting cells; disruption of efficient specific immunity; and the immune responses used for parasite proliferation.

  7. Effects of preoperative and postoperative enteral nutrition on postoperative nutritional status and immune function of gastric cancer patients.

    Science.gov (United States)

    Ding, Dayong; Feng, Ye; Song, Bin; Gao, Shuohui; Zhao, Jisheng

    2015-03-01

    Effects of preoperative one week enteral nutrition (EN) support on the postoperative nutritional status, immune function and inflammatory response of gastric cancer patients were investigated. 106 cases of gastric cancer patients were randomly divided into preoperative one week EN group (trial group) and early postoperative EN group (control group), which were continuously treated with EN support until the postoperative 9th day according to different treatment protocols. All the patients were checked for their body weight, skinfold thickness, upper arm circumference, white blood cell count (WBC), albumin (ALB), prealbumin (PA), C-reactive protein (CRP), humoral immunity (IgA, IgG), T cell subsets (CD4, CD8 and CD4/CD8), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), etc. on the preoperative and the postoperative 1st and 10th day, respectively. PA and IgG levels of the experimental group were higher than those of the control group on the postoperative 10th day, whereas IL-6 level of the experimental group was lower than that of the control group. EN support for preoperative gastric cancer patients will improve the postoperative nutritional status and immune function, alleviate inflammatory response, and facilitate the recovery of patients.

  8. Staphylococcal Immune Evasion Proteins: Structure, Function, and Host Adaptation.

    Science.gov (United States)

    Koymans, Kirsten J; Vrieling, Manouk; Gorham, Ronald D; van Strijp, Jos A G

    2017-01-01

    Staphylococcus aureus is a successful human and animal pathogen. Its pathogenicity is linked to its ability to secrete a large amount of virulence factors. These secreted proteins interfere with many critical components of the immune system, both innate and adaptive, and hamper proper immune functioning. In recent years, numerous studies have been conducted in order to understand the molecular mechanism underlying the interaction of evasion molecules with the host immune system. Structural studies have fundamentally contributed to our understanding of the mechanisms of action of the individual factors. Furthermore, such studies revealed one of the most striking characteristics of the secreted immune evasion molecules: their conserved structure. Despite high-sequence variability, most immune evasion molecules belong to a small number of structural categories. Another remarkable characteristic is that S. aureus carries most of these virulence factors on mobile genetic elements (MGE) or ex-MGE in its accessory genome. Coevolution of pathogen and host has resulted in immune evasion molecules with a highly host-specific function and prevalence. In this review, we explore how these shared structures and genomic locations relate to function and host specificity. This is discussed in the context of therapeutic options for these immune evasion molecules in infectious as well as in inflammatory diseases.

  9. Host immune cellular reactions in corneal neovascularization

    Directory of Open Access Journals (Sweden)

    Nizar S. Abdelfattah

    2016-04-01

    Full Text Available Corneal neovascularization (CNV is a global important cause of visual impairment. The immune mechanisms leading to corneal heme- and lymphangiogenesis have been extensively studied over the past years as more attempts were made to develop better prophylactic and therapeutic measures. This article aims to discuss immune cells of particular relevance to CNV, with a focus on macrophages, Th17 cells, dendritic cells and the underlying immunology of common pathologies involving neovascularization of the cornea. Hopefully, a thorough understanding of these topics would propel the efforts to halt the detrimental effects of CNV.

  10. Escaping Deleterious Immune Response in Their Hosts: Lessons from Trypanosomatids

    Science.gov (United States)

    Geiger, Anne; Bossard, Géraldine; Sereno, Denis; Pissarra, Joana; Lemesre, Jean-Loup; Vincendeau, Philippe; Holzmuller, Philippe

    2016-01-01

    The Trypanosomatidae family includes the genera Trypanosoma and Leishmania, protozoan parasites displaying complex digenetic life cycles requiring a vertebrate host and an insect vector. Trypanosoma brucei gambiense, Trypanosoma cruzi, and Leishmania spp. are important human pathogens causing human African trypanosomiasis (HAT or sleeping sickness), Chagas’ disease, and various clinical forms of Leishmaniasis, respectively. They are transmitted to humans by tsetse flies, triatomine bugs, or sandflies, and affect millions of people worldwide. In humans, extracellular African trypanosomes (T. brucei) evade the hosts’ immune defenses, allowing their transmission to the next host, via the tsetse vector. By contrast, T. cruzi and Leishmania sp. have developed a complex intracellular lifestyle, also preventing several mechanisms to circumvent the host’s immune response. This review seeks to set out the immune evasion strategies developed by the different trypanosomatids resulting from parasite–host interactions and will focus on: clinical and epidemiological importance of diseases; life cycles: parasites–hosts–vectors; innate immunity: key steps for trypanosomatids in invading hosts; deregulation of antigen-presenting cells; disruption of efficient specific immunity; and the immune responses used for parasite proliferation. PMID:27303406

  11. Effect of immune nutritional support on immune function and inflammatory factor in postoperative patients with gastric cancer

    Directory of Open Access Journals (Sweden)

    Hua-Jia Dai

    2016-05-01

    Full Text Available Objective: To investigate the effect of immune nutritional support on immune function and inflammatory factor in postoperative patients with gastric cancer. Methods: A total of 100 patients with gastric cancer were selected and randomly divided into the observation group and the control group with 50 cases in each group. The control group received routine perioperative enteral and parenteral nutrition, on the basis of conventional nutritional support, and the observation group was given enteral nutrition emulsion immune support. Then, the immune function and the inflammatory factor of postoperative day 1 and day 7 were compared between the two groups. Results: (1 With the preoperative data as the basis, the levels of serum IgG, IgA, C3 and C4 decreased at the postoperative day 1 and then increased at the postoperative day 7, while the level of IgM showed an increasing trend and then a decreasing trend in the two groups, and the corresponding figures for the postoperative day 1 and day 7 were statistically different between the two groups. In the observation group, the levels of IgG, IgA, C3 and C4 were higher, while the level of IgM was lower at the postoperative day 1 and day 7 than that in the control group, and the differences were statistically significant; (2 With the preoperative data as the basis, the levels of serum TNF-α, IL-6 and CRP significantly increased at the postoperative day 1 and then decreased at the postoperative day 7 in the two groups, and the corresponding figures for the postoperative day 1 and day 7 in the observation group were lower than those in the control group, and the differences were statistically significant. Conclusion: Immune nutritional support can help to reduce the damage of immune function and the inflammatory response induced by surgery in patients with gastric cancer, which is worthy of clinical application.

  12. Characterization of host immune responses in Ebola virus infections.

    Science.gov (United States)

    Wong, Gary; Kobinger, Gary P; Qiu, Xiangguo

    2014-06-01

    Ebola causes highly lethal hemorrhagic fever in humans with no licensed countermeasures. Its virulence can be attributed to several immunoevasion mechanisms: an early inhibition of innate immunity started by the downregulation of type I interferon, epitope masking and subversion of the adaptive humoural immunity by secreting a truncated form of the viral glycoprotein. Deficiencies in specific and non-specific antiviral responses result in unrestricted viral replication and dissemination in the host, causing death typically within 10 days after the appearance of symptoms. This review summarizes the host immune response to Ebola infection, and highlights the short- and long-term immune responses crucial for protection, which holds implications for the design of future vaccines and therapeutics.

  13. Host-microbiota interplay in mediating immune disorders.

    Science.gov (United States)

    Felix, Krysta M; Tahsin, Shekha; Wu, Hsin-Jung Joyce

    2018-04-01

    To maintain health, the immune system must maintain a delicate balance between eliminating invading pathogens and avoiding immune disorders such as autoimmunity and allergies. The gut microbiota provide essential health benefits to the host, particularly by regulating immune homeostasis. Dysbiosis, an alteration and imbalance of the gut microbiota, is associated with the development of several autoimmune diseases in both mice and humans. In this review, we discuss recent advances in understanding how certain factors, such as age and gender, affect the gut microbiota, which in turn can influence the development of autoimmune diseases. The age factor in microbiota-dependent immune disorders indicates a window of opportunity for future diagnostic and therapeutic approaches. We also discuss unique commensal bacteria with strong immunomodulatory activity. Finally, we provide an overview of the potential molecular mechanisms whereby gut microbiota induce autoimmunity, as well as the evidence that gut microbiota trigger extraintestinal diseases by inducing the migration of gut-derived immune cells. Elucidating the interaction of gut microbiota and the host immune system will help us understand the pathogenesis of immune disorders, and provide us with new foundations to develop novel immuno- or microbe-targeted therapies. © 2017 New York Academy of Sciences.

  14. The host immune response to Clostridium difficile infection

    Science.gov (United States)

    2013-01-01

    Clostridium difficile infection (CDI) is the most common infectious cause of healthcare-acquired diarrhoea. Outcomes of C. difficile colonization are varied, from asymptomatic carriage to fulminant colitis and death, due in part to the interplay between the pathogenic virulence factors of the bacterium and the counteractive immune responses of the host. Secreted toxins A and B are the major virulence factors of C. difficile and induce a profound inflammatory response by intoxicating intestinal epithelial cells causing proinflammatory cytokine release. Host cell necrosis, vascular permeability and neutrophil infiltration lead to an elevated white cell count, profuse diarrhoea and in severe cases, dehydration, hypoalbuminaemia and toxic megacolon. Other bacterial virulence factors, including surface layer proteins and flagella proteins, are detected by host cell surface signal molecules that trigger downstream cell-mediated immune pathways. Human studies have identified a role for serum and faecal immunoglobulin levels in protection from disease, but the recent development of a mouse model of CDI has enabled studies into the precise molecular interactions that trigger the immune response during infection. Key effector molecules have been identified that can drive towards a protective anti-inflammatory response or a damaging proinflammatory response. The limitations of current antimicrobial therapies for CDI have led to the development of both active and passive immunotherapies, none of which have, as yet been formally approved for CDI. However, recent advances in our understanding of the molecular basis of host immune protection against CDI may provide an exciting opportunity for novel therapeutic developments in the future. PMID:25165542

  15. Tumor - host immune interactions in Ewing sarcoma : implications for therapy

    NARCIS (Netherlands)

    Berghuis, Dagmar

    2012-01-01

    In this thesis, we report on various aspects of tumor - host (immune) interactions in Ewing sarcoma patients with the aim to obtain leads for immunotherapeutic or targeted treatment strategies. We demonstrate a key role for interferon gamma (IFNg) in enhancing both Ewing sarcoma immunogenicity and

  16. Dual oxidase in mucosal immunity and host-microbe homeostasis.

    Science.gov (United States)

    Bae, Yun Soo; Choi, Myoung Kwon; Lee, Won-Jae

    2010-07-01

    Mucosal epithelia are in direct contact with microbes, which range from beneficial symbionts to pathogens. Accordingly, hosts must have a conflicting strategy to combat pathogens efficiently while tolerating symbionts. Recent progress has revealed that dual oxidase (DUOX) plays a key role in mucosal immunity in organisms that range from flies to humans. Information from the genetic model of Drosophila has advanced our understanding of the regulatory mechanism of DUOX and its role in mucosal immunity. Further investigations of DUOX regulation in response to symbiotic or non-symbiotic bacteria and the in vivo consequences in host physiology will give a novel insight into the microbe-controlling system of the mucosa. Copyright 2010 Elsevier Ltd. All rights reserved.

  17. Pathogens and host immunity in the ancient human oral cavity

    Science.gov (United States)

    Warinner, Christina; Matias Rodrigues, João F.; Vyas, Rounak; Trachsel, Christian; Shved, Natallia; Grossmann, Jonas; Radini, Anita; Hancock, Y.; Tito, Raul Y.; Fiddyment, Sarah; Speller, Camilla; Hendy, Jessica; Charlton, Sophy; Luder, Hans Ulrich; Salazar-García, Domingo C.; Eppler, Elisabeth; Seiler, Roger; Hansen, Lars; Samaniego Castruita, José Alfredo; Barkow-Oesterreicher, Simon; Teoh, Kai Yik; Kelstrup, Christian; Olsen, Jesper V.; Nanni, Paolo; Kawai, Toshihisa; Willerslev, Eske; von Mering, Christian; Lewis, Cecil M.; Collins, Matthew J.; Gilbert, M. Thomas P.; Rühli, Frank; Cappellini, Enrico

    2014-01-01

    Calcified dental plaque (dental calculus) preserves for millennia and entraps biomolecules from all domains of life and viruses. We report the first high-resolution taxonomic and protein functional characterization of the ancient oral microbiome and demonstrate that the oral cavity has long served as a reservoir for bacteria implicated in both local and systemic disease. We characterize: (i) the ancient oral microbiome in a diseased state, (ii) 40 opportunistic pathogens, (iii) the first evidence of ancient human-associated putative antibiotic resistance genes, (iv) a genome reconstruction of the periodontal pathogen Tannerella forsythia, (v) 239 bacterial and 43 human proteins, allowing confirmation of a long-term association between host immune factors, “red-complex” pathogens, and periodontal disease, and (vi) DNA sequences matching dietary sources. Directly datable and nearly ubiquitous, dental calculus permits the simultaneous investigation of pathogen activity, host immunity, and diet, thereby extending the direct investigation of common diseases into the human evolutionary past. PMID:24562188

  18. New Players in Immunity to Tuberculosis: The Host Microbiome, Lung Epithelium, and Innate Immune Cells

    Science.gov (United States)

    Gupta, Nancy; Kumar, Rakesh; Agrawal, Babita

    2018-01-01

    Tuberculosis (TB) is a highly contagious infection and devastating chronic disease, causing 10.4 million new infections and 1.8 million deaths every year globally. Efforts to control and eradicate TB are hampered by the rapid emergence of drug resistance and limited efficacy of the only available vaccine, BCG. Immunological events in the airways and lungs are of major importance in determining whether exposure to Mycobacterium tuberculosis (Mtb) results in successful infection or protective immunity. Several studies have demonstrated that the host microbiota is in constant contact with the immune system, and thus continually directs the nature of immune responses occurring during new infections. However, little is known about its role in the eventual outcome of the mycobacterial infection. In this review, we highlight the changes in microbial composition in the respiratory tract and gut that have been linked to the alteration of immune responses, and to the risk, prevention, and treatment of TB. In addition, we summarize our current understanding of alveolar epithelial cells and the innate immune system, and their interaction with Mtb during early infection. Extensive studies are warranted to fully understand the all-inclusive role of the lung microbiota, its interaction with epithelium and innate immune responses and resulting adaptive immune responses, and in the pathogenesis and/or protection from Mtb infection. Novel interventions aimed at influencing the microbiota, the alveolar immune system and innate immunity will shape future strategies of prevention and treatment for TB. PMID:29692778

  19. Yersinia type III effectors perturb host innate immune responses

    Science.gov (United States)

    Pha, Khavong; Navarro, Lorena

    2016-01-01

    The innate immune system is the first line of defense against invading pathogens. Innate immune cells recognize molecular patterns from the pathogen and mount a response to resolve the infection. The production of proinflammatory cytokines and reactive oxygen species, phagocytosis, and induced programmed cell death are processes initiated by innate immune cells in order to combat invading pathogens. However, pathogens have evolved various virulence mechanisms to subvert these responses. One strategy utilized by Gram-negative bacterial pathogens is the deployment of a complex machine termed the type III secretion system (T3SS). The T3SS is composed of a syringe-like needle structure and the effector proteins that are injected directly into a target host cell to disrupt a cellular response. The three human pathogenic Yersinia spp. (Y. pestis, Y. enterocolitica, and Y. pseudotuberculosis) are Gram-negative bacteria that share in common a 70 kb virulence plasmid which encodes the T3SS. Translocation of the Yersinia effector proteins (YopE, YopH, YopT, YopM, YpkA/YopO, and YopP/J) into the target host cell results in disruption of the actin cytoskeleton to inhibit phagocytosis, downregulation of proinflammatory cytokine/chemokine production, and induction of cellular apoptosis of the target cell. Over the past 25 years, studies on the Yersinia effector proteins have unveiled tremendous knowledge of how the effectors enhance Yersinia virulence. Recently, the long awaited crystal structure of YpkA has been solved providing further insights into the activation of the YpkA kinase domain. Multisite autophosphorylation by YpkA to activate its kinase domain was also shown and postulated to serve as a mechanism to bypass regulation by host phosphatases. In addition, novel Yersinia effector protein targets, such as caspase-1, and signaling pathways including activation of the inflammasome were identified. In this review, we summarize the recent discoveries made on Yersinia

  20. Regulation of host metabolism and immunity by the gut microbiome

    DEFF Research Database (Denmark)

    Laursen, Janne Marie

    During recent years, central roles of the gut microbiome in metabolic and immunological diseases have been uncovered, and multiple studies have shown that bacterial-derived components shape host physiology and immune responses via direct cellular interactions. The intestinal immune system...... developed a computational framework for identifying bacteria that produce specific endotoxin variants with opposing immunological effects in metagenomic fecal samples. This framework was used to identify the endotoxin variant distribution amongst bacteria in the gut microbiome of Danes and Chinese...... with obesity and type 2 diabetes. We show for the first time that species producing pro-inflammatory endotoxin variants are vastly underrepresented in the gut microbiome compared to species producing non-inflammatory endotoxin and we identify country-specific gram-negative bacterial modules associated...

  1. Pathogens and host immunity in the ancient human oral cavity

    DEFF Research Database (Denmark)

    Warinner, Christina; Rodrigues, João F Matias; Vyas, Rounak

    2014-01-01

    Calcified dental plaque (dental calculus) preserves for millennia and entraps biomolecules from all domains of life and viruses. We report the first, to our knowledge, high-resolution taxonomic and protein functional characterization of the ancient oral microbiome and demonstrate that the oral...... cavity has long served as a reservoir for bacteria implicated in both local and systemic disease. We characterize (i) the ancient oral microbiome in a diseased state, (ii) 40 opportunistic pathogens, (iii) ancient human-associated putative antibiotic resistance genes, (iv) a genome reconstruction...... calculus permits the simultaneous investigation of pathogen activity, host immunity and diet, thereby extending direct investigation of common diseases into the human evolutionary past....

  2. DNA Tumor Virus Regulation of Host DNA Methylation and Its Implications for Immune Evasion and Oncogenesis.

    Science.gov (United States)

    Kuss-Duerkop, Sharon K; Westrich, Joseph A; Pyeon, Dohun

    2018-02-13

    Viruses have evolved various mechanisms to evade host immunity and ensure efficient viral replication and persistence. Several DNA tumor viruses modulate host DNA methyltransferases for epigenetic dysregulation of immune-related gene expression in host cells. The host immune responses suppressed by virus-induced aberrant DNA methylation are also frequently involved in antitumor immune responses. Here, we describe viral mechanisms and virus-host interactions by which DNA tumor viruses regulate host DNA methylation to evade antiviral immunity, which may contribute to the generation of an immunosuppressive microenvironment during cancer development. Recent trials of immunotherapies have shown promising results to treat multiple cancers; however, a significant number of non-responders necessitate identifying additional targets for cancer immunotherapies. Thus, understanding immune evasion mechanisms of cancer-causing viruses may provide great insights for reversing immune suppression to prevent and treat associated cancers.

  3. DNA Tumor Virus Regulation of Host DNA Methylation and Its Implications for Immune Evasion and Oncogenesis

    Directory of Open Access Journals (Sweden)

    Sharon K. Kuss-Duerkop

    2018-02-01

    Full Text Available Viruses have evolved various mechanisms to evade host immunity and ensure efficient viral replication and persistence. Several DNA tumor viruses modulate host DNA methyltransferases for epigenetic dysregulation of immune-related gene expression in host cells. The host immune responses suppressed by virus-induced aberrant DNA methylation are also frequently involved in antitumor immune responses. Here, we describe viral mechanisms and virus–host interactions by which DNA tumor viruses regulate host DNA methylation to evade antiviral immunity, which may contribute to the generation of an immunosuppressive microenvironment during cancer development. Recent trials of immunotherapies have shown promising results to treat multiple cancers; however, a significant number of non-responders necessitate identifying additional targets for cancer immunotherapies. Thus, understanding immune evasion mechanisms of cancer-causing viruses may provide great insights for reversing immune suppression to prevent and treat associated cancers.

  4. Pteromalus puparum venom impairs host cellular immune responses by decreasing expression of its scavenger receptor gene

    Science.gov (United States)

    Insect host/parasitoid interactions are co-evolved systems in which host defenses are balanced by parasitoid mechanisms to disable or hide from host immune effectors. Although there is a rich literature on these systems, parasitoid immune-disabling mechanisms have not been fully elucidated. Here we ...

  5. Regulation of stem-cell mediated host immunity by the sphingolipid ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Regulation of stem-cell mediated host immunity by the sphingolipid pathway ... in the generation of mature immune cells and the functioning of the surrounding ... methods with human cells and genetically engineered mice to examine how the ...

  6. Gut Microbiota Co-microevolution with Selection for Host Humoral Immunity

    Directory of Open Access Journals (Sweden)

    Lingyu Yang

    2017-07-01

    Full Text Available To explore coevolution between the gut microbiota and the humoral immune system of the host, we used chickens as the model organism. The host populations were two lines (HAS and LAS developed from a common founder that had undergone 40 generations of divergent selection for antibody titers to sheep red blood cells (SRBC and two relaxed sublines (HAR and LAR. Analysis revealed that microevolution of host humoral immunity contributed to the composition of gut microbiota at the taxa level. Relaxing selection enriched some microorganisms whose functions were opposite to host immunity. Particularly, Ruminococcaceae and Oscillospira enriched in high antibody relaxed (HAR and contributed to reduction in antibody response, while Lactobacillus increased in low antibody relaxed (LAR and elevated the antibody response. Microbial functional analysis showed that alterations were involved in pathways relating to the immune system and infectious diseases. Our findings demonstrated co-microevolution relationships of host-microbiota and that gut microorganisms influenced host immunity.

  7. Patterns of oligonucleotide sequences in viral and host cell RNA identify mediators of the host innate immune system.

    Directory of Open Access Journals (Sweden)

    Benjamin D Greenbaum

    Full Text Available The innate immune response provides a first line of defense against pathogens by targeting generic differential features that are present in foreign organisms but not in the host. These innate responses generate selection forces acting both in pathogens and hosts that further determine their co-evolution. Here we analyze the nucleic acid sequence fingerprints of these selection forces acting in parallel on both host innate immune genes and ssRNA viral genomes. We do this by identifying dinucleotide biases in the coding regions of innate immune response genes in plasmacytoid dendritic cells, and then use this signal to identify other significant host innate immune genes. The persistence of these biases in the orthologous groups of genes in humans and chickens is also examined. We then compare the significant motifs in highly expressed genes of the innate immune system to those in ssRNA viruses and study the evolution of these motifs in the H1N1 influenza genome. We argue that the significant under-represented motif pattern of CpG in an AU context--which is found in both the ssRNA viruses and innate genes, and has decreased throughout the history of H1N1 influenza replication in humans--is immunostimulatory and has been selected against during the co-evolution of viruses and host innate immune genes. This shows how differences in host immune biology can drive the evolution of viruses that jump into species with different immune priorities than the original host.

  8. DMPD: Macrophage migration inhibitory factor and host innate immune responses tomicrobes. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 14620137 Macrophage migration inhibitory factor and host innate immune responses to...microbes. Calandra T. Scand J Infect Dis. 2003;35(9):573-6. (.png) (.svg) (.html) (.csml) Show Macrophage migration... inhibitory factor and host innate immune responses tomicrobes. PubmedID 14620137 Title Macrophage migration

  9. Treg cell-IgA axis in maintenance of host immune homeostasis with microbiota

    OpenAIRE

    Feng, Ting; Elson, Charles O.; Cong, Yingzi

    2010-01-01

    The intestine is the home to a vast diversity of microbiota and a complex of mucosal immune system. Multiple regulatory mechanisms control host immune responses to microbiota and maintain intestinal immune homeostasis. This mini review will provide evidence indicating a Treg cell-IgA axis and such axis playing a major role in maintenance of intestinal homeostasis.

  10. Long-term effect of postoperative irradiation on the immune functions in patients with mammary carcinoma

    International Nuclear Information System (INIS)

    Toivanen, A.; Nordman, E.

    1981-01-01

    The effect of postoperative irradiation on the immune functions of 13 patients with breast carcinoma is reported, using as parameters the peipheral blood lymphocyte count, percentages of E and EAC rosette forming cells, and lymphocyte proliferative responses to PHA, Con A and PPD. After irradiation the number of peripheral blood lymphocytes was reduced during 8 months. The percentages of E and EAC rosette forming cells were not altered during the observation time of 7 to 36 months. In the proliferative responses of lymphocytes to PHA, Con A and PPD, the postoperative irradiation caused a decrease which, regarding PHA and Con A, lasted up to 8 months and then recovered. The decrease in the proliferative responses to PPD was stronger and lasted during the whole observation time. In the mitogenic responses of patients with recurrent or disseminating disease no difference could be demonstrated as compared with the patients living recurrence-free. (Auth.)

  11. Impact of enteral nutrition on postoperative immune function and nutritional status.

    Science.gov (United States)

    Wang, F; Hou, M X; Wu, X L; Bao, L D; Dong, P D

    2015-06-10

    We studied the effects of enteral nutrition (EN) support initiated 1 week before surgery on postoperative nutritional status, immune function, and inflammatory response in gastric cancer patients. A total of 200 gastric cancer patients were randomly divided into two groups: EN starting 1 week before surgery (study group) and EN starting early after surgery (control group). The two groups received EN support, following different therapeutic schedules, until the 9th day after operation. In the patients, body weight, skinfold thickness, upper-arm circumference, white blood cell count, albumin, prealbumin, C-reactive protein, peripheral immunoglobulins (IgA, IgG, and IgM), T lymphocyte subsets, interleukin-6, and tumor necrosis factor-α were measured 10 days before and after surgery and on the first day after surgery. There was no statistically significant difference in the results of recovery time of passage of gas by anus, abdominal distension, stomachache, blood glucose, hepatic and renal functions, and electrolytes between the two groups of patients (P > 0. 05). Adverse reactions occurred to both groups at 1 and 2 days after operation. Such conditions was improved after the intravenous drip rate was adjusted. The albumin and prealbumin levels of the patients in both groups decreased at 1 day after operation (P gastric cancer patients can improve their postoperative nutritional status and immune function, can reduce inflammatory response, and is more conducive to the recovery of patients.

  12. Patterns of early gut colonization shape future immune responses of the host

    DEFF Research Database (Denmark)

    Hansen, Camilla Hartmann Friis; Nielsen, Dennis Sandris; Kverka, Miloslav

    2012-01-01

    The most important trigger for immune system development is the exposure to microbial components immediately after birth. Moreover, targeted manipulation of the microbiota can be used to change host susceptibility to immune-mediated diseases. Our aim was to analyze how differences in early gut...... production. In conclusion, a time window exists that enables the artificial colonization of GF mice by a single oral dose of caecal content, which may modify the future immune phenotype of the host. Moreover, delayed microbial colonization of the gut causes permanent changes in the immune system....

  13. Host immunity to Mycobacterium tuberculosis and risk of tuberculosis

    DEFF Research Database (Denmark)

    Michelsen, Sascha Wilk; Soborg, Bolette; Agger, Else-Marie

    2016-01-01

    BACKGROUND: Human immune responses to latent Mycobacterium tuberculosis (Mtb) infection (LTBI) may enable individuals to control Mtb infection and halt progression to tuberculosis (TB), a hypothesis applied in several novel TB vaccines. We aimed to evaluate whether immune responses to selected LTBI...

  14. Innate Immunity Evasion by Enteroviruses: Insights into Virus-Host Interaction

    Directory of Open Access Journals (Sweden)

    Xiaobo Lei

    2016-01-01

    Full Text Available Enterovirus genus includes multiple important human pathogens, such as poliovirus, coxsackievirus, enterovirus (EV A71, EV-D68 and rhinovirus. Infection with EVs can cause numerous clinical conditions including poliomyelitis, meningitis and encephalitis, hand-foot-and-mouth disease, acute flaccid paralysis, diarrhea, myocarditis and respiratory illness. EVs, which are positive-sense single-stranded RNA viruses, trigger activation of the host antiviral innate immune responses through pathogen recognition receptors such as retinoic acid-inducible gene (RIG-I-likeand Toll-like receptors. In turn, EVs have developed sophisticated strategies to evade host antiviral responses. In this review, we discuss the interplay between the host innate immune responses and EV infection, with a primary focus on host immune detection and protection against EV infection and viral strategies to evade these antiviral immune responses.

  15. Host range, immunity and antigenic properties of lambdoid coliphage HK97.

    Science.gov (United States)

    Dhillon, E K; Dhillon, T S; Lai, A N; Linn, S

    1980-09-01

    Temperate coliphage HK97 was isolated from pig dung. Although HK97 is antigenically unrelated to coliphage lambda, it has similar morphology, host range and immunity properties, and can recombine with it.

  16. Epigenetic modulation of host: new insights into immune evasion

    Indian Academy of Sciences (India)

    MADHU

    regulation of gene expression is intrinsically active inside the host and is involved in regulating gene expression and .... self from non-self, helps the packaging of the viral DNA ..... with DNA as genetic material, and having the potential to.

  17. Glycan gimmickry by parasitic helminths: a strategy for modulating the host immune response?

    Science.gov (United States)

    van Die, Irma; Cummings, Richard D

    2010-01-01

    Parasitic helminths (worms) co-evolved with vertebrate immune systems to enable long-term survival of worms in infected hosts. Among their survival strategies, worms use their glycans within glycoproteins and glycolipids, which are abundant on helminth surfaces and in their excretory/ secretory products, to regulate and suppress host immune responses. Many helminths express unusual and antigenic (nonhost-like) glycans, including those containing polyfucose, tyvelose, terminal GalNAc, phosphorylcholine, methyl groups, and sugars in unusual linkages. In addition, some glycan antigens are expressed that share structural features with those in their intermediate and vertebrate hosts (host-like glycans), including Le(X) (Galbeta1-4[Fucalpha1-3]GlcNAc-), LDNF (GalNAcbeta1-4[Fucalpha1-3]GlcNAc-), LDN (GalNAcbeta1-4GlcNAc-), and Tn (GalNAcalpha1-O-Thr/Ser) antigens. The expression of host-like glycan determinants is remarkable and suggests that helminths may gain advantages by synthesizing such glycans. The expression of host-like glycans by parasites previously led to the concept of "molecular mimicry," in which molecules are either derived from the pathogen or acquired from the host to evade recognition by the host immune system. However, recent discoveries into the potential of host glycan-binding proteins (GBPs), such as C-type lectin receptors and galectins, to functionally interact with various host-like helminth glycans provide new insights. Host GBPs through their interactions with worm-derived glycans participate in shaping innate and adaptive immune responses upon infection. We thus propose an alternative concept termed "glycan gimmickry," which is defined as an active strategy of parasites to use their glycans to target GBPs within the host to promote their survival.

  18. Comparative Proteomics Identifies Host Immune System Proteins Affected by Infection with Mycobacterium bovis.

    Directory of Open Access Journals (Sweden)

    Vladimir López

    2016-03-01

    Full Text Available Mycobacteria of the Mycobacterium tuberculosis complex (MTBC greatly impact human and animal health worldwide. The mycobacterial life cycle is complex, and the mechanisms resulting in pathogen infection and survival in host cells are not fully understood. Eurasian wild boar (Sus scrofa are natural reservoir hosts for MTBC and a model for mycobacterial infection and tuberculosis (TB. In the wild boar TB model, mycobacterial infection affects the expression of innate and adaptive immune response genes in mandibular lymph nodes and oropharyngeal tonsils, and biomarkers have been proposed as correlates with resistance to natural infection. However, the mechanisms used by mycobacteria to manipulate host immune response are not fully characterized. Our hypothesis is that the immune system proteins under-represented in infected animals, when compared to uninfected controls, are used by mycobacteria to guarantee pathogen infection and transmission. To address this hypothesis, a comparative proteomics approach was used to compare host response between uninfected (TB- and M. bovis-infected young (TB+ and adult animals with different infection status [TB lesions localized in the head (TB+ or affecting multiple organs (TB++]. The results identified host immune system proteins that play an important role in host response to mycobacteria. Calcium binding protein A9, Heme peroxidase, Lactotransferrin, Cathelicidin and Peptidoglycan-recognition protein were under-represented in TB+ animals when compared to uninfected TB- controls, but protein levels were higher as infection progressed in TB++ animals when compared to TB- and/or TB+ adult wild boar. MHCI was the only protein over-represented in TB+ adult wild boar when compared to uninfected TB- controls. The results reported here suggest that M. bovis manipulates host immune response by reducing the production of immune system proteins. However, as infection progresses, wild boar immune response recovers to

  19. Comparative Proteomics Identifies Host Immune System Proteins Affected by Infection with Mycobacterium bovis.

    Science.gov (United States)

    López, Vladimir; Villar, Margarita; Queirós, João; Vicente, Joaquín; Mateos-Hernández, Lourdes; Díez-Delgado, Iratxe; Contreras, Marinela; Alves, Paulo C; Alberdi, Pilar; Gortázar, Christian; de la Fuente, José

    2016-03-01

    Mycobacteria of the Mycobacterium tuberculosis complex (MTBC) greatly impact human and animal health worldwide. The mycobacterial life cycle is complex, and the mechanisms resulting in pathogen infection and survival in host cells are not fully understood. Eurasian wild boar (Sus scrofa) are natural reservoir hosts for MTBC and a model for mycobacterial infection and tuberculosis (TB). In the wild boar TB model, mycobacterial infection affects the expression of innate and adaptive immune response genes in mandibular lymph nodes and oropharyngeal tonsils, and biomarkers have been proposed as correlates with resistance to natural infection. However, the mechanisms used by mycobacteria to manipulate host immune response are not fully characterized. Our hypothesis is that the immune system proteins under-represented in infected animals, when compared to uninfected controls, are used by mycobacteria to guarantee pathogen infection and transmission. To address this hypothesis, a comparative proteomics approach was used to compare host response between uninfected (TB-) and M. bovis-infected young (TB+) and adult animals with different infection status [TB lesions localized in the head (TB+) or affecting multiple organs (TB++)]. The results identified host immune system proteins that play an important role in host response to mycobacteria. Calcium binding protein A9, Heme peroxidase, Lactotransferrin, Cathelicidin and Peptidoglycan-recognition protein were under-represented in TB+ animals when compared to uninfected TB- controls, but protein levels were higher as infection progressed in TB++ animals when compared to TB- and/or TB+ adult wild boar. MHCI was the only protein over-represented in TB+ adult wild boar when compared to uninfected TB- controls. The results reported here suggest that M. bovis manipulates host immune response by reducing the production of immune system proteins. However, as infection progresses, wild boar immune response recovers to limit pathogen

  20. The Mannose Receptor in Regulation of Helminth-Mediated Host Immunity

    Directory of Open Access Journals (Sweden)

    Irma van Die

    2017-11-01

    Full Text Available Infection with parasitic helminths affects humanity and animal welfare. Parasitic helminths have the capacity to modulate host immune responses to promote their survival in infected hosts, often for a long time leading to chronic infections. In contrast to many infectious microbes, however, the helminths are able to induce immune responses that show positive bystander effects such as the protection to several immune disorders, including multiple sclerosis, inflammatory bowel disease, and allergies. They generally promote the generation of a tolerogenic immune microenvironment including the induction of type 2 (Th2 responses and a sub-population of alternatively activated macrophages. It is proposed that this anti-inflammatory response enables helminths to survive in their hosts and protects the host from excessive pathology arising from infection with these large pathogens. In any case, there is an urgent need to enhance understanding of how helminths beneficially modulate inflammatory reactions, to identify the molecules involved and to promote approaches to exploit this knowledge for future therapeutic interventions. Evidence is increasing that C-type lectins play an important role in driving helminth-mediated immune responses. C-type lectins belong to a large family of calcium-dependent receptors with broad glycan specificity. They are abundantly present on immune cells, such as dendritic cells and macrophages, which are essential in shaping host immune responses. Here, we will focus on the role of the C-type lectin macrophage mannose receptor (MR in helminth–host interactions, which is a critically understudied area in the field of helminth immunobiology. We give an overview of the structural aspects of the MR including its glycan specificity, and the functional implications of the MR in helminth–host interactions focusing on a few selected helminth species.

  1. [Effects of Early Enteral Immunonutrition on Postoperative Immune Function and Rehabilitation of Patients with Gastric Cancer and Nutritional Risk].

    Science.gov (United States)

    Peng, Chang-Bing; Li, Wen-Zhong; Xu, Rui; Zhuang, Wen

    2017-05-01

    To investigate the effects of early enteral immunonutrition on postoperative immune function and rehabilitation of gastric cancer patients with nutritional risk. New hospitalized patients with gastric cancer were evaluated the nutrient status based on NRS 2002. The patients who scored between 3 to 5 points were randomized into two groups(30 cases for each group), and those in experimental group were given 7-d early postoperative enteral immune nutrition, those in control group were given normal nutrition. The immune indexes (CD3 + , CD4 + , CD8 + and CD4 + /CD8 + ) and nutritional indexes(transferrin, pre-albumin, albumin) were measured before operation and at the 3 rd and 7 th day postoperatively. In addition, the first flatus time, gastrointestinal adverse reactions and complications, length of hospital stays were compared between the two groups. The level of CD4 + /CD8 + and transferrin, pre-albumin, albumin in experimental group were significantly higher than those in control group at the third and seventh day postoperatively ( P 0.05). Early enteral immunonutrition can effectively promote the recovery of nutritional status and immune function in gastric cancer patients with nutrition risk.

  2. Immune Checkpoint Targets for Host-Directed Therapy to Prevent and Treat Leishmaniasis

    Directory of Open Access Journals (Sweden)

    Rajiv Kumar

    2017-11-01

    Full Text Available Leishmaniasis encompasses a group of diseases caused by protozoan parasites belonging to the genus Leishmania. These diseases range from life threatening visceral forms to self-healing cutaneous lesions, and each disease manifestations can progress to complications involving dissemination of parasites to skin or mucosal tissue. A feature of leishmaniasis is the key role host immune responses play in disease outcome. T cells are critical for controlling parasite growth. However, they can also contribute to disease onset and progression. For example, potent regulatory T cell responses can develop that suppress antiparasitic immunity. Alternatively, hyperactivated CD4+ or CD8+ T cells can be generated that cause damage to host tissues. There is no licensed human vaccine and drug treatment options are often limited and problematic. Hence, there is an urgent need for new strategies to improve the efficacy of current vaccine candidates and/or enhance both antiparasitic drug effectiveness and subsequent immunity in treated individuals. Here, we describe our current understanding about host immune responses contributing to disease protection and progression in the various forms of leishmaniasis. We also discuss how this knowledge may be used to develop new strategies for host-directed immune therapy to prevent or treat leishmaniasis. Given the major advances made in immune therapy in the cancer and autoimmune fields in recent years, there are significant opportunities to ride on the back of these successes in the infectious disease domain. Conversely, the rapid progress in our understanding about host immune responses during leishmaniasis is also providing opportunities to develop novel immunotherapy strategies that could have broad applications in diseases characterized by inflammation or immune dysfunction.

  3. Effects of bestatin on the host immunity in patients treated for urogenital cancer

    International Nuclear Information System (INIS)

    Ozono, S.; Iwai, A.; Babaya, K.; Hiramatsu, T.; Yoshida, K.; Yamada, K.; Hirao, Y.; Aoyama, H.; Ohara, S.; Okajima, E.

    1990-01-01

    To examine effects of bestatin on the host immunity of patients with urogenital cancer, 54 patients were randomized into 2 groups: bestatin treated and controls. In each group, the patients were divided into 2 subgroups: one which received basic treatment expected to greatly affect host immunity ('invasive treatment') while the other one received other types of basic treatment ('non-invasive treatment'). Peripheral lymphocyte, OKT 4/8 ratio and purified protein derivative (PPD) skin reaction were used as immunological markers. There were significant differences in the 'invasive' treatment group between bestatin treated patients and controls concerning lymphocyte counts and PPD skin reactions and in the 'non-invasive' group concerning lymphocyte counts and OKT 4/8 ratios. These results suggest that bestatin may potentiate host immunity in patients with urogenital cancer. Further studies on larger materials are, however, needed before more definite conclusions can be drawn. (orig.)

  4. Diet and host-microbial crosstalk in postnatal intestinal immune homeostasis.

    Science.gov (United States)

    Jain, Nitya; Walker, W Allan

    2015-01-01

    Neonates face unique challenges in the period following birth. The postnatal immune system is in the early stages of development and has a range of functional capabilities that are distinct from the mature adult immune system. Bidirectional immune-microbial interactions regulate the development of mucosal immunity and alter the composition of the microbiota, which contributes to overall host well-being. In the past few years, nutrition has been highlighted as a third element in this interaction that governs host health by modulating microbial composition and the function of the immune system. Dietary changes and imbalances can disturb the immune-microbiota homeostasis, which might alter susceptibility to several autoimmune and metabolic diseases. Major changes in cultural traditions, socioeconomic status and agriculture are affecting the nutritional status of humans worldwide, which is altering core intestinal microbial communities. This phenomenon is especially relevant to the neonatal and paediatric populations, in which the microbiota and immune system are extremely sensitive to dietary influences. In this Review, we discuss the current state of knowledge regarding early-life nutrition, its effects on the microbiota and the consequences of diet-induced perturbation of the structure of the microbial community on mucosal immunity and disease susceptibility.

  5. Ironing Out the Wrinkles in Host Defense: Interactions between Iron Homeostasis and Innate Immunity

    Science.gov (United States)

    Wang, Lijian; Cherayil, Bobby J.

    2009-01-01

    Iron is an essential micronutrient for both microbial pathogens and their mammalian hosts. Changes in iron availability and distribution have significant effects on pathogen virulence and on the immune response to infection. Recent advances in our understanding of the molecular regulation of iron metabolism have shed new light on how alterations in iron homeostasis both contribute to and influence innate immunity. In this article, we review what is currently known about the role of iron in the response to infection. PMID:20375603

  6. Homologous recombination deficiency and host anti-tumor immunity in triple-negative breast cancer.

    Science.gov (United States)

    Telli, M L; Stover, D G; Loi, S; Aparicio, S; Carey, L A; Domchek, S M; Newman, L; Sledge, G W; Winer, E P

    2018-05-07

    Triple-negative breast cancer (TNBC) is associated with worse outcomes relative to other breast cancer subtypes. Chemotherapy remains the standard-of-care systemic therapy for patients with localized or metastatic disease, with few biomarkers to guide benefit. We will discuss recent advances in our understanding of two key biological processes in TNBC, homologous recombination (HR) DNA repair deficiency and host anti-tumor immunity, and their intersection. Recent advances in our understanding of homologous recombination (HR) deficiency, including FDA approval of PARP inhibitor olaparib for BRCA1 or BRCA2 mutation carriers, and host anti-tumor immunity in TNBC offer potential for new and biomarker-driven approaches to treat TNBC. Assays interrogating HR DNA repair capacity may guide treatment with agents inducing or targeting DNA damage repair. Tumor infiltrating lymphocytes (TILs) are associated with improved prognosis in TNBC and recent efforts to characterize infiltrating immune cell subsets and activate host anti-tumor immunity offer promise, yet challenges remain particularly in tumors lacking pre-existing immune infiltrates. Advances in these fields provide potential biomarkers to stratify patients with TNBC and guide therapy: induction of DNA damage in HR-deficient tumors and activation of existing or recruitment of host anti-tumor immune cells. Importantly, these advances provide an opportunity to guide use of existing therapies and development of novel therapies for TNBC. Efforts to combine therapies that exploit HR deficiency to enhance the activity of immune-directed therapies offer promise. HR deficiency remains an important biomarker target and potentially effective adjunct to enhance immunogenicity of 'immune cold' TNBCs.

  7. The entomopathogenic fungus Nomuraea rileyi impairs cellular immunity of its host Helicoverpa armigera.

    Science.gov (United States)

    Zhong, Ke; Liu, Zhan-Chi; Wang, Jia-Lin; Liu, Xu-Sheng

    2017-09-01

    In this study, we investigated the effect of the entomopathogenic fungus Nomuraea rileyi on Helicoverpa armigera cellular immune responses. Nomuraea rileyi infection had no effect on total hemocyte count (THC), but impaired hemocyte-mediated phagocytosis, nodulation, and encapsulation responses. Nomuraea rileyi infection led to a significant reduction in hemocyte spreading. An in vitro assay revealed that plasma from N. rileyi infected H. armigera larvae suppressed the spreading ability of hemocytes from naïve larvae. We infer that N. rileyi suppresses the cellular immune response of its host, possibly by secreting exogenous, cytotoxic compounds into the host's hemolymph. © 2017 Wiley Periodicals, Inc.

  8. Resiniferatoxin modulates the Th1 immune response and protects the host during intestinal nematode infection.

    Science.gov (United States)

    Muñoz-Carrillo, J L; Contreras-Cordero, J F; Muñoz-López, J L; Maldonado-Tapia, C H; Muñoz-Escobedo, J J; Moreno-García, M A

    2017-09-01

    In the early stage of the intestinal phase of Trichinella spiralis infection, the host triggers a Th1-type immune response with the aim of eliminating the parasite. However, this response damages the host which favours the survival of the parasite. In the search for novel pharmacological strategies that inhibit the Th1 immune response and assist the host against T. spiralis infection, a recent study showed that resiniferatoxin had anti-inflammatory activity contributed to the host in T. spiralis infection. In this study, we evaluated whether RTX modulates the host immune response through the inhibition of Th1 cytokines in the intestinal phase. In addition, it was determined whether the treatment with RTX affects the infectivity of T. spiralis-L1 and the development of the T. spiralis life cycle. Our results show that RTX decreased serum levels of IL-12, INF-γ, IL-1β, TNF-α and parasite burden on muscle tissue. It was observed that T. spiralis-L1 treated with RTX decreased their infectivity affecting the development of the T. spiralis life cycle in mouse. These results demonstrate that RTX is able to inhibit the production of Th1 cytokines, contributing to the defence against T. spiralis, which places it as a potential drug modulator of the immune response. © 2017 John Wiley & Sons Ltd.

  9. Polar lipids of Burkholderia pseudomallei induce different host immune responses.

    Directory of Open Access Journals (Sweden)

    Mercedes Gonzalez-Juarrero

    Full Text Available Melioidosis is a disease in tropical and subtropical regions of the world that is caused by Burkholderia pseudomallei. In endemic regions the disease occurs primarily in humans and goats. In the present study, we used the goat as a model to dissect the polar lipids of B. pseudomallei to identify lipid molecules that could be used for adjuvants/vaccines or as diagnostic tools. We showed that the lipidome of B. pseudomallei and its fractions contain several polar lipids with the capacity to elicit different immune responses in goats, namely rhamnolipids and ornithine lipids which induced IFN-γ, whereas phospholipids and an undefined polar lipid induced strong IL-10 secretion in CD4(+ T cells. Autologous T cells co-cultured with caprine dendritic cells (cDCs and polar lipids of B. pseudomallei proliferated and up-regulated the expression of CD25 (IL-2 receptor molecules. Furthermore, we demonstrated that polar lipids were able to up-regulate CD1w2 antigen expression in cDCs derived from peripheral blood monocytes. Interestingly, the same polar lipids had only little effect on the expression of MHC class II DR antigens in the same caprine dendritic cells. Finally, antibody blocking of the CD1w2 molecules on cDCs resulted in decreased expression for IFN-γ by CD4(+ T cells. Altogether, these results showed that polar lipids of B. pseudomallei are recognized by the caprine immune system and that their recognition is primarily mediated by the CD1 antigen cluster.

  10. Polar Lipids of Burkholderia pseudomallei Induce Different Host Immune Responses

    Science.gov (United States)

    Gonzalez-Juarrero, Mercedes; Mima, Naoko; Trunck, Lily A.; Schweizer, Herbert P.; Bowen, Richard A.; Dascher, Kyle; Mwangi, Waithaka; Eckstein, Torsten M.

    2013-01-01

    Melioidosis is a disease in tropical and subtropical regions of the world that is caused by Burkholderia pseudomallei. In endemic regions the disease occurs primarily in humans and goats. In the present study, we used the goat as a model to dissect the polar lipids of B. pseudomallei to identify lipid molecules that could be used for adjuvants/vaccines or as diagnostic tools. We showed that the lipidome of B. pseudomallei and its fractions contain several polar lipids with the capacity to elicit different immune responses in goats, namely rhamnolipids and ornithine lipids which induced IFN-γ, whereas phospholipids and an undefined polar lipid induced strong IL-10 secretion in CD4+ T cells. Autologous T cells co-cultured with caprine dendritic cells (cDCs) and polar lipids of B. pseudomallei proliferated and up-regulated the expression of CD25 (IL-2 receptor) molecules. Furthermore, we demonstrated that polar lipids were able to up-regulate CD1w2 antigen expression in cDCs derived from peripheral blood monocytes. Interestingly, the same polar lipids had only little effect on the expression of MHC class II DR antigens in the same caprine dendritic cells. Finally, antibody blocking of the CD1w2 molecules on cDCs resulted in decreased expression for IFN-γ by CD4+ T cells. Altogether, these results showed that polar lipids of B. pseudomallei are recognized by the caprine immune system and that their recognition is primarily mediated by the CD1 antigen cluster. PMID:24260378

  11. Both live and dead Enterococci activate Caenorhabditis elegans host defense via immune and stress pathways.

    Science.gov (United States)

    Yuen, Grace J; Ausubel, Frederick M

    2018-12-31

    The innate immune response of the nematode Caenorhabditis elegans has been extensively studied and a variety of Toll-independent immune response pathways have been identified. Surprisingly little, however, is known about how pathogens activate the C. elegans immune response. Enterococcus faecalis and Enterococcus faecium are closely related enterococcal species that exhibit significantly different levels of virulence in C. elegans infection models. Previous work has shown that activation of the C. elegans immune response by Pseudomonas aeruginosa involves P. aeruginosa-mediated host damage. Through ultrastructural imaging, we report that infection with either E. faecalis or E. faecium causes the worm intestine to become distended with proliferating bacteria in the absence of extensive morphological changes and apparent physical damage. Genetic analysis, whole-genome transcriptional profiling, and multiplexed gene expression analysis demonstrate that both enterococcal species, whether live or dead, induce a rapid and similar transcriptional defense response dependent upon previously described immune signaling pathways. The host response to E. faecium shows a stricter dependence upon stress response signaling pathways than the response to E. faecalis. Unexpectedly, we find that E. faecium is a C. elegans pathogen and that an active wild-type host defense response is required to keep an E. faecium infection at bay. These results provide new insights into the mechanisms underlying the C. elegans immune response to pathogen infection.

  12. Modelling parasite transmission in a grazing system: the importance of host behaviour and immunity.

    Directory of Open Access Journals (Sweden)

    Naomi J Fox

    Full Text Available Parasitic helminths present one of the most pervasive challenges to grazing herbivores. Many macro-parasite transmission models focus on host physiological defence strategies, omitting more complex interactions between hosts and their environments. This work represents the first model that integrates both the behavioural and physiological elements of gastro-intestinal nematode transmission dynamics in a managed grazing system. A spatially explicit, individual-based, stochastic model is developed, that incorporates both the hosts' immunological responses to parasitism, and key grazing behaviours including faecal avoidance. The results demonstrate that grazing behaviour affects both the timing and intensity of parasite outbreaks, through generating spatial heterogeneity in parasite risk and nutritional resources, and changing the timing of exposure to the parasites' free-living stages. The influence of grazing behaviour varies with the host-parasite combination, dependent on the development times of different parasite species and variations in host immune response. Our outputs include the counterintuitive finding that under certain conditions perceived parasite avoidance behaviours (faecal avoidance can increase parasite risk, for certain host-parasite combinations. Through incorporating the two-way interaction between infection dynamics and grazing behaviour, the potential benefits of parasite-induced anorexia are also demonstrated. Hosts with phenotypic plasticity in grazing behaviour, that make grazing decisions dependent on current parasite burden, can reduce infection with minimal loss of intake over the grazing season. This paper explores how both host behaviours and immunity influence macro-parasite transmission in a spatially and temporally heterogeneous environment. The magnitude and timing of parasite outbreaks is influenced by host immunity and behaviour, and the interactions between them; the incorporation of both regulatory processes

  13. The Value of a Comparative Approach to Understand the Complex Interplay between Microbiota and Host Immunity

    Directory of Open Access Journals (Sweden)

    Norma M. Morella

    2017-09-01

    Full Text Available The eukaryote immune system evolved and continues to evolve within a microbial world, and as such is critically shaped by—and in some cases even reliant upon—the presence of host-associated microbial species. There are clear examples of adaptations that allow the host to simultaneously tolerate and/or promote growth of symbiotic microbiota while protecting itself against pathogens, but the relationship between immunity and the microbiome reaches far beyond simple recognition and includes complex cross talk between host and microbe as well as direct microbiome-mediated protection against pathogens. Here, we present a broad but brief overview of how the microbiome is controlled by and interacts with diverse immune systems, with the goal of identifying questions that can be better addressed by taking a comparative approach across plants and animals and different types of immunity. As two key examples of such an approach, we focus on data examining the importance of early exposure on microbiome tolerance and immune system development and function, and the importance of transmission among hosts in shaping the potential coevolution between, and long-term stability of, host–microbiome associations. Then, by comparing existing evidence across short-lived plants, mouse model systems and humans, and insects, we highlight areas of microbiome research that are strong in some systems and absent in others with the hope of guiding future research that will allow for broad-scale comparisons moving forward. We argue that such an approach will not only help with identification of generalities in host–microbiome–immune interactions but also improve our understanding of the role of the microbiome in host health.

  14. A Trematode Parasite Derived Growth Factor Binds and Exerts Influences on Host Immune Functions via Host Cytokine Receptor Complexes.

    Directory of Open Access Journals (Sweden)

    Azad A Sulaiman

    2016-11-01

    Full Text Available The trematode Fasciola hepatica is responsible for chronic zoonotic infection globally. Despite causing a potent T-helper 2 response, it is believed that potent immunomodulation is responsible for rendering this host reactive non-protective host response thereby allowing the parasite to remain long-lived. We have previously identified a growth factor, FhTLM, belonging to the TGF superfamily can have developmental effects on the parasite. Herein we demonstrate that FhTLM can exert influence over host immune functions in a host receptor specific fashion. FhTLM can bind to receptor members of the Transforming Growth Factor (TGF superfamily, with a greater affinity for TGF-β RII. Upon ligation FhTLM initiates the Smad2/3 pathway resulting in phenotypic changes in both fibroblasts and macrophages. The formation of fibroblast CFUs is reduced when cells are cultured with FhTLM, as a result of TGF-β RI kinase activity. In parallel the wound closure response of fibroblasts is also delayed in the presence of FhTLM. When stimulated with FhTLM blood monocyte derived macrophages adopt an alternative or regulatory phenotype. They express high levels interleukin (IL-10 and arginase-1 while displaying low levels of IL-12 and nitric oxide. Moreover they also undergo significant upregulation of the inhibitory receptor PD-L1 and the mannose receptor. Use of RNAi demonstrates that this effect is dependent on TGF-β RII and mRNA knock-down leads to a loss of IL-10 and PD-L1. Finally, we demonstrate that FhTLM aids newly excysted juveniles (NEJs in their evasion of antibody-dependent cell cytotoxicity (ADCC by reducing the NO response of macrophages-again dependent on TGF-β RI kinase. FhTLM displays restricted expression to the F. hepatica gut resident NEJ stages. The altered fibroblast responses would suggest a role for dampened tissue repair responses in facilitating parasite migration. Furthermore, the adoption of a regulatory macrophage phenotype would allow

  15. Host control of malaria infections: constraints on immune and erythropoeitic response kinetics.

    Directory of Open Access Journals (Sweden)

    Philip G McQueen

    2008-08-01

    Full Text Available The two main agents of human malaria, Plasmodium vivax and Plasmodium falciparum, can induce severe anemia and provoke strong, complex immune reactions. Which dynamical behaviors of host immune and erythropoietic responses would foster control of infection, and which would lead to runaway parasitemia and/or severe anemia? To answer these questions, we developed differential equation models of interacting parasite and red blood cell (RBC populations modulated by host immune and erythropoietic responses. The model immune responses incorporate both a rapidly responding innate component and a slower-responding, long-term antibody component, with several parasite developmental stages considered as targets for each type of immune response. We found that simulated infections with the highest parasitemia tended to be those with ineffective innate immunity even if antibodies were present. We also compared infections with dyserythropoiesis (reduced RBC production during infection to those with compensatory erythropoiesis (boosted RBC production or a fixed basal RBC production rate. Dyserythropoiesis tended to reduce parasitemia slightly but at a cost to the host of aggravating anemia. On the other hand, compensatory erythropoiesis tended to reduce the severity of anemia but with enhanced parasitemia if the innate response was ineffective. For both parasite species, sharp transitions between the schizont and the merozoite stages of development (i.e., with standard deviation in intra-RBC development time immune response, though P. vivax attacks a much smaller subset of RBCs. Since most P. vivax infections are nonlethal (if debilitating clinically, this suggests that P

  16. A bacterial E3 ubiquitin ligase targets a host protein kinase to disrupt plant immunity.

    Science.gov (United States)

    Rosebrock, Tracy R; Zeng, Lirong; Brady, Jennifer J; Abramovitch, Robert B; Xiao, Fangming; Martin, Gregory B

    2007-07-19

    Many bacterial pathogens of plants and animals use a type III secretion system to deliver diverse virulence-associated 'effector' proteins into the host cell. The mechanisms by which these effectors act are mostly unknown; however, they often promote disease by suppressing host immunity. One type III effector, AvrPtoB, expressed by the plant pathogen Pseudomonas syringae pv. tomato, has a carboxy-terminal domain that is an E3 ubiquitin ligase. Deletion of this domain allows an amino-terminal region of AvrPtoB (AvrPtoB(1-387)) to be detected by certain tomato varieties leading to immunity-associated programmed cell death. Here we show that a host kinase, Fen, physically interacts with AvrPtoB(1-387 )and is responsible for activating the plant immune response. The AvrPtoB E3 ligase specifically ubiquitinates Fen and promotes its degradation in a proteasome-dependent manner. This degradation leads to disease susceptibility in Fen-expressing tomato lines. Various wild species of tomato were found to exhibit immunity in response to AvrPtoB(1-387 )and not to full-length AvrPtoB. Thus, by acquiring an E3 ligase domain, AvrPtoB has thwarted a highly conserved host resistance mechanism.

  17. Enhanced host immune recognition of E.coli causing mastitis in CD-14 transgenic mice.

    Science.gov (United States)

    Escherchia coli causes mastitis, an economically significant disease in dairy animals. E. coli endotoxin (lipopolysaccharide, LPS) when bound by host membrane proteins such as CD-14, causes release of pro-inflammatory cytokines recruiting neutrophils as a early innate immune response. Excessive pr...

  18. Recent progress in understanding host immune response to Avian Coccidiosis: Th1 and Th17 responses

    Science.gov (United States)

    Host-pathogen interaction leading to protection against coccidiosis is complex, involving many aspects of innate and adaptive immunity to intracellular parasites. The etiologic agent of avian coccidiosis is Eimeria, a genus of eukaryotic obligate intracellular parasites belonging to the phylum Apico...

  19. Gut Immune Maturation Depends on Colonization with a Host-Specific Microbiota

    Science.gov (United States)

    Chung, Hachung; Pamp, Sünje J.; Hill, Jonathan A.; Surana, Neeraj K.; Edelman, Sanna M.; Troy, Erin B.; Reading, Nicola C.; Villablanca, Eduardo J.; Wang, Sen; Mora, Jorge R.; Umesaki, Yoshinori; Mathis, Diane; Benoist, Christophe; Relman, David A.; Kasper, Dennis L.

    2012-01-01

    SUMMARY Gut microbial induction of host immune maturation exemplifies host-microbe mutualism. We colonized germ-free (GF) mice with mouse microbiota (MMb) or human microbiota (HMb) to determine whether small intestinal immune maturation depends on a coevolved host-specific microbiota. Gut bacterial numbers and phylum abundance were similar in MMb and HMb mice, but bacterial species differed, especially the Firmicutes. HMb mouse intestines had low levels of CD4+ and CD8+ T cells, few proliferating T cells, few dendritic cells, and low antimicrobial peptide expression–all characteristics of GF mice. Rat microbiota also failed to fully expand intestinal T cell numbers in mice. Colonizing GF or HMb mice with mouse-segmented filamentous bacteria (SFB) partially restored T cell numbers, suggesting that SFB and other MMb organisms are required for full immune maturation in mice. Importantly, MMb conferred better protection against Salmonella infection than HMb. A host-specific microbiota appears to be critical for a healthy immune system. PMID:22726443

  20. Efficacy of multiple anticancer therapies may depend on host immune response

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    Kritika Karri

    2017-06-01

    Full Text Available The host immune system is a key player in anticancer therapy response and resistance. Although the impact of host immune response in the ‘war against cancer’ has been studied and it has been the basis for immunotherapy, understanding of its role in attenuating the action of conventional anticancer therapies is an area that has not been fully explored. In spite of advances in systemic therapy, the 5-year survival rate for adenocarcinoma is still a mere 13% and the primary reason for treatment failure is believed to be due to acquired resistance to therapy. Hence, there is a need for identifying reliable biomarkers for guided treatment of lung and colon adenocarcinoma and to better predict the outcomes of specific anticancer therapies. In this work, gene expression data were analyzed using public resources and this study shows how host immune competence underscores the efficacy of various anticancer therapies. Additionally, the result provides insight on the regulation of certain biochemical pathways relating to the immune system, and suggests that smart chemotherapeutic intervention strategies could be based on a patient’s immune profile.

  1. Symbiotic and antibiotic interactions between gut commensal microbiota and host immune system

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    Mantas Kazimieras Malys

    2015-01-01

    Full Text Available The human gut commensal microbiota forms a complex population of microorganisms that survive by maintaining a symbiotic relationship with the host. Amongst the metabolic benefits it brings, formation of adaptive immune system and maintenance of its homeostasis are functions that play an important role. This review discusses the integral elements of commensal microbiota that stimulate responses of different parts of the immune system and lead to health or disease. It aims to establish conditions and factors that contribute to gut commensal microbiota's transformation from symbiotic to antibiotic relationship with human. We suggest that the host-microbiota relationship has been evolved to benefit both parties and any changes that may lead to disease, are not due to unfriendly properties of the gut microbiota but due to host genetics or environmental changes such as diet or infection.

  2. The Host Immune Response to Streptococcus pneumoniae: Bridging Innate and Adaptive Immunity

    Science.gov (United States)

    2006-07-06

    P.J. (1989) Effect of Streptococcus pneumoniae on human respiratory epithelium in vitro. Infect. Immun. 57: 2006-2013. Stoop, J.N., van der Molen ...antibiotics. Clin. Microbiol. Rev. 3: 171-196. Knapp, S., Wieland, C.W., van ’t Veer, C., Takeuchi, O., Akira, S., Florquin, S., and van der Poll...R.G., Baan, C.C., van der Laan, L.J., Kuipers, E.J., Kusters, J.G., and Janssen, H.L. (2005) Regulatory T cells contribute to the impaired immune

  3. Interaction Between 2 Nutraceutical Treatments and Host Immune Status in the Pediatric Critical Illness Stress-Induced Immune Suppression Comparative Effectiveness Trial.

    Science.gov (United States)

    Carcillo, Joseph A; Dean, J Michael; Holubkov, Richard; Berger, John; Meert, Kathleen L; Anand, Kanwaljeet J S; Zimmerman, Jerry J; Newth, Christopher J L; Harrison, Rick; Burr, Jeri; Willson, Douglas F; Nicholson, Carol; Bell, Michael J; Berg, Robert A; Shanley, Thomas P; Heidemann, Sabrina M; Dalton, Heidi; Jenkins, Tammara L; Doctor, Allan; Webster, Angie; Tamburro, Robert F

    2017-11-01

    The pediatric Critical Illness Stress-induced Immune Suppression (CRISIS) trial compared the effectiveness of 2 nutraceutical supplementation strategies and found no difference in the development of nosocomial infection and sepsis in the overall population. We performed an exploratory post hoc analysis of interaction between nutraceutical treatments and host immune status related to the development of nosocomial infection/sepsis. Children from the CRISIS trial were analyzed according to 3 admission immune status categories marked by decreasing immune competence: immune competent without lymphopenia, immune competent with lymphopenia, and previously immunocompromised. The comparative effectiveness of the 2 treatments was analyzed for interaction with immune status category. There were 134 immune-competent children without lymphopenia, 79 previously immune-competent children with lymphopenia, and 27 immunocompromised children who received 1 of the 2 treatments. A significant interaction was found between treatment arms and immune status on the time to development of nosocomial infection and sepsis ( P patient characteristic.

  4. Effect of host nutrition on immunity and local immune response of rabbits to Obeliscoides cuniculi

    International Nuclear Information System (INIS)

    Sinski, E.; Bezubik, B.; Wedrychowicz, H.; Szklarczyk, J.; Doligalska, M.

    1988-01-01

    In a series of experiments carried out on young and adult rabbits the effect of isocaloric low protein diets containing 4% or 8% protein compared with a diet containing 21% protein on Obeliscoides cuniculi infection was studied. The pathogenesis, resistance and local immunity were assessed after single infections with 10,000 larvae or reinfection with 5000 larvae. Live weight gain was reduced in young and adult rabbits fed the low protein diets, but the establishment of parasites was not substantially influenced by protein deprivation. However, development of worms in the histotrophic phase and parasite fecundity were impaired in association with the low protein diet. Moreover, mild anaemia as well as changes in the mucosal immune response as a result of infection were related to the level of dietary protein. (author). 30 refs, 6 figs, 5 tabs

  5. Effect of thoracoscopic esophagus cancer surgery on postoperative incision pain as well as non-specific and specific immune response

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    Jin-Long Wu1

    2017-04-01

    Full Text Available Objective: To explore the effect of thoracoscopic esophagus cancer surgery on postoperative incision pain as well as non-specific and specific immune response. Methods: 56 patients with esophageal cancer who accepted surgical treatment in our hospital between March 2011 and February 2016 were collected, the operation methods and related laboratory tests were reviewed, and then they were divided into the thoracoscope group (n=27 who accepted thoracoscopic surgery and the open surgery group (n=29 who accepted traditional thoracotomy. Before operation and 1 d after operation, immune scatter turbidimetry was used to detect serum levels of pain mediators, and flow cytometer was used to detect the levels of nonspecific immune indexes and specific immune indexes. Results: Before operation, the differences in serum pain mediators as well as nonspecific immune response and specific immune response indexes were not statistically significant between two groups of patients (P>0.05. 1 d after operation, serum pain mediators 5-HT, K+ and NE levels of thoracoscope group were lower than those of open surgery group (P<0.05; nonspecific immune response indexes NK cell as well as C3 and C4 levels in peripheral blood of thoracoscope group were significantly higher than those of open surgery group (P<0.05; specific immune response indexes CD4+, CD4+/CD8+, IgA and IgG levels in peripheral blood of thoracoscope group were significantly higher than those of open surgery group (P<0.05. Conclusion: Thoracoscopic esophagus cancer surgery causes less damage, has lighter inhibition on the immune response system, and is an ideal operation method for patients with early middle esophagus cancer.

  6. Tumor suppressor maspin as a modulator of host immune response to cancer

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    Sijana H. Dzinic

    2015-10-01

    Full Text Available Despite the promising clinical outcome, the primary challenge of the curative cancer immunotherapy is to overcome the dichotomy of the immune response: tumor-evoked immunostimulatory versus tumor-induced immunosuppressive. The goal needs to be two-fold, to re-establish sustainable antitumor-cancer immunity and to eliminate immunosuppression. The successful elimination of cancer cells by immunosurveillance requires the antigenic presentation of the tumor cells or tumor-associated antigens and the expression of immunostimulatory cytokines and chemokines by cancer and immune cells. Tumors are heterogeneous and as such, some of the tumor cells are thought to have stem cell characteristics that enable them to suppress or desensitize the host immunity due to acquired epigenetic changes. A central mechanism underlying tumor epigenetic instability is the increased histone deacetylase (HDAC-mediated repression of HDAC-target genes regulating homeostasis and differentiation. It was noted that pharmacological HDAC inhibitors are not effective in eliminating tumor cells partly because they may induce immunosuppression. We have shown that epithelial-specific tumor suppressor maspin, an ovalbumin-like non-inhibitory serine protease inhibitor, reprograms tumor cells toward better differentiated phenotypes by inhibiting HDAC1. Recently, we uncovered a novel function of maspin in directing host immunity towards tumor elimination. In this review, we discuss the maspin and maspin/HDAC1 interplay in tumor biology and immunology. We propose that maspin based therapies may eradicate cancer.

  7. Gastrointestinal helminths may affect host susceptibility to anthrax through seasonal immune trade-offs.

    Science.gov (United States)

    Cizauskas, Carrie A; Turner, Wendy C; Wagner, Bettina; Küsters, Martina; Vance, Russell E; Getz, Wayne M

    2014-11-12

    Most vertebrates experience coinfections, and many pathogen-pathogen interactions occur indirectly through the host immune system. These interactions are particularly strong in mixed micro-macroparasite infections because of immunomodulatory effects of helminth parasites. While these trade-offs have been examined extensively in laboratory animals, few studies have examined them in natural systems. Additionally, many wildlife pathogens fluctuate seasonally, at least partly due to seasonal host immune changes. We therefore examined seasonality of immune resource allocation, pathogen abundance and exposure, and interactions between infections and immunity in plains zebra (Equus quagga) in Etosha National Park (ENP), Namibia, a system with strongly seasonal patterns of gastrointestinal (GI) helminth infection intensity and concurrent anthrax outbreaks. Both pathogens are environmentally transmitted, and helminth seasonality is driven by environmental pressures on free living life stages. The reasons behind anthrax seasonality are currently not understood, though anthrax is less likely directly driven by environmental factors. We measured a complex, interacting set of variables and found evidence that GI helminth infection intensities, eosinophil counts, IgE and IgGb antibody titers, and possibly IL-4 cytokine signaling were increased in wetter seasons, and that ectoparasite infestations and possibly IFN-γ cytokine signaling were increased in drier seasons. Monocyte counts and anti-anthrax antibody titers were negatively associated with wet season eosinophilia, and monocytes were negatively correlated with IgGb and IgE titers. Taken together, this supports the hypothesis that ENP wet seasons are characterized by immune resource allocation toward Th-2 type responses, while Th1-type immunity may prevail in drier seasons, and that hosts may experience Th1-Th2 trade-offs. We found evidence that this Th2-type resource allocation is likely driven by GI parasite infections

  8. Modulation of Host Immunity by Human Respiratory Syncytial Virus Virulence Factors: A Synergic Inhibition of Both Innate and Adaptive Immunity

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    Gisela Canedo-Marroquín

    2017-08-01

    Full Text Available The Human Respiratory Syncytial Virus (hRSV is a major cause of acute lower respiratory tract infections (ARTIs and high rates of hospitalizations in children and in the elderly worldwide. Symptoms of hRSV infection include bronchiolitis and pneumonia. The lung pathology observed during hRSV infection is due in part to an exacerbated host immune response, characterized by immune cell infiltration to the lungs. HRSV is an enveloped virus, a member of the Pneumoviridae family, with a non-segmented genome and negative polarity-single RNA that contains 10 genes encoding for 11 proteins. These include the Fusion protein (F, the Glycoprotein (G, and the Small Hydrophobic (SH protein, which are located on the virus surface. In addition, the Nucleoprotein (N, Phosphoprotein (P large polymerase protein (L part of the RNA-dependent RNA polymerase complex, the M2-1 protein as a transcription elongation factor, the M2-2 protein as a regulator of viral transcription and (M protein all of which locate inside the virion. Apart from the structural proteins, the hRSV genome encodes for the non-structural 1 and 2 proteins (NS1 and NS2. HRSV has developed different strategies to evade the host immunity by means of the function of some of these proteins that work as virulence factors to improve the infection in the lung tissue. Also, hRSV NS-1 and NS-2 proteins have been shown to inhibit the activation of the type I interferon response. Furthermore, the hRSV nucleoprotein has been shown to inhibit the immunological synapsis between the dendritic cells and T cells during infection, resulting in an inefficient T cell activation. Here, we discuss the hRSV virulence factors and the host immunological features raised during infection with this virus.

  9. The cytoskeleton in cell-autonomous immunity: structural determinants of host defence

    Science.gov (United States)

    Mostowy, Serge; Shenoy, Avinash R.

    2016-01-01

    Host cells use antimicrobial proteins, pathogen-restrictive compartmentalization and cell death in their defence against intracellular pathogens. Recent work has revealed that four components of the cytoskeleton — actin, microtubules, intermediate filaments and septins, which are well known for their roles in cell division, shape and movement — have important functions in innate immunity and cellular self-defence. Investigations using cellular and animal models have shown that these cytoskeletal proteins are crucial for sensing bacteria and for mobilizing effector mechanisms to eliminate them. In this Review, we highlight the emerging roles of the cytoskeleton as a structural determinant of cell-autonomous host defence. PMID:26292640

  10. Impact of visceral obesity and metabolic syndrome on the postoperative immune, inflammatory, and endocrine response following surgery for esophageal adenocarcinoma.

    Science.gov (United States)

    Doyle, S L; Mongan, A M; Donohoe, C L; Pidgeon, G P; Sherlock, M; Reynolds, J V; Lysaght, J

    2017-06-01

    Visceral obesity and metabolic syndrome (MetSyn) represent a constellation of inflammation, insulin resistance, and hyperglycemia and are established risk factors for gastrointestinal cancer. However, their impact on the immune and inflammatory response after major upper gastrointestinal oncologic surgery is unknown. In 125 consecutive patients who underwent esophagectomy, C-reactive protein (CRP) and CRP:albumin levels were recorded preoperatively and on days 1, 3, 7, and 14 postoperatively. In a subset of 30 patients, circulating levels of IL-6, IL-8, IL-10, IL-12p70, IFN-γ, TNF-α, TGF-β, and cortisol were measured. Incidences of postoperative complications were prospectively recorded. In the study cohort, 51% of patients were viscerally obese, 40.7% had MetSyn, and 33.6% were hyperglycemic. Viscerally obese and MetSyn-positive patients demonstrated greater postoperative CRP levels and CRP:albumin levels on day 7 and day 14 compared with nonobese and MetSyn-negative patients (P levels of cortisol were observed in the viscerally obese and hyperglycemic patients compared to nonobese and normoglycemic patients. No association was observed between visceral obesity, MetSyn or hyperglycemia, and postoperative cytokine profile. Viscerally obese patients had an increased overall incidence of postoperative complications compared to nonobese patients (67.2% vs. 47.5%, P = 0.031) on univariate but not multivariate analysis (P = 0.078) and visceral obesity was not associated with an increased incidence of specific complications. Visceral obesity, MetSyn, and hyperglycemia are prevalent in patients undergoing major upper gastrointestinal resection and are associated with an exaggerated acute-phase inflammatory response postoperatively. Further research is warranted to determine whether this association is directly causal. © The Authors 2017. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For

  11. Structural modifications of bacterial lipopolysaccharide that facilitate Gram-negative bacteria evasion of host innate immunity

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    Motohiro eMatsuura

    2013-05-01

    Full Text Available Bacterial lipopolysaccharide (LPS, a cell wall component characteristic of Gram-negative bacteria, is a representative pathogen-associated molecular pattern that allows mammalian cells to recognize bacterial invasion and trigger innate immune responses. The polysaccharide moiety of LPS primary plays protective roles for bacteria such as prevention from complement attacks or camouflage with common host carbohydrate residues. The lipid moiety, termed lipid A, is recognized by the Toll-like receptor 4 (TLR4/MD-2 complex, which transduces signals for activation of host innate immunity. The basic structure of lipid A is a glucosamine disaccharide substituted by phosphate groups and acyl groups. Lipid A with 6 acyl groups (hexa-acylated form has been indicated to be a strong stimulator of the TLR4/MD-2 complex. This type of lipid A is conserved among a wide variety of Gram-negative bacteria, and those bacteria are easily recognized by host cells for activation of defensive innate immune responses. Modifications of the lipid A structure to less-acylated forms have been observed in some bacterial species, and those forms are poor stimulators of the TLR4/MD-2 complex. Such modifications are thought to facilitate bacterial evasion of host innate immunity, thereby enhancing pathogenicity. This hypothesis is supported by studies of Yersinia pestis LPS, which contains hexa-acylated lipid A when the bacterium grows at 27ºC (the temperature of the vector flea, and shifts to contain less-acylated forms when grown at the human body temperature of 37ºC. This alteration of lipid A forms following transmission of Y. pestis from fleas to humans contributes predominantly to the virulence of this bacterium over other virulence factors. A similar role for less-acylated lipid A forms has been indicated in some other bacterial species, such as Francisella tularensis, Helicobacter pylori, and Porphyromonas gingivalis, and further studies to explore this concept are

  12. Analyses of Brucella Pathogenesis, Host Immunity, and Vaccine Targets using Systems Biology and Bioinformatics

    OpenAIRE

    He, Yongqun

    2012-01-01

    Brucella is a Gram-negative, facultative intracellular bacterium that causes zoonotic brucellosis in humans and various animals. Out of 10 classified Brucella species, B. melitensis, B. abortus, B. suis, and B. canis are pathogenic to humans. In the past decade, the mechanisms of Brucella pathogenesis and host immunity have been extensively investigated using the cutting edge systems biology and bioinformatics approaches. This article provides a comprehensive review of the applications of Omi...

  13. Pseudomonas syringae evades host immunity by degrading flagellin monomers with alkaline protease AprA.

    Science.gov (United States)

    Pel, Michiel J C; van Dijken, Anja J H; Bardoel, Bart W; Seidl, Michael F; van der Ent, Sjoerd; van Strijp, Jos A G; Pieterse, Corné M J

    2014-07-01

    Bacterial flagellin molecules are strong inducers of innate immune responses in both mammals and plants. The opportunistic pathogen Pseudomonas aeruginosa secretes an alkaline protease called AprA that degrades flagellin monomers. Here, we show that AprA is widespread among a wide variety of bacterial species. In addition, we investigated the role of AprA in virulence of the bacterial plant pathogen P. syringae pv. tomato DC3000. The AprA-deficient DC3000 ΔaprA knockout mutant was significantly less virulent on both tomato and Arabidopsis thaliana. Moreover, infiltration of A. thaliana Col-0 leaves with DC3000 ΔaprA evoked a significantly higher level of expression of the defense-related genes FRK1 and PR-1 than did wild-type DC3000. In the flagellin receptor mutant fls2, pathogen virulence and defense-related gene activation did not differ between DC3000 and DC3000 ΔaprA. Together, these results suggest that AprA of DC3000 is important for evasion of recognition by the FLS2 receptor, allowing wild-type DC3000 to be more virulent on its host plant than AprA-deficient DC3000 ΔaprA. To provide further evidence for the role of DC3000 AprA in host immune evasion, we overexpressed the AprA inhibitory peptide AprI of DC3000 in A. thaliana to counteract the immune evasive capacity of DC3000 AprA. Ectopic expression of aprI in A. thaliana resulted in an enhanced level of resistance against wild-type DC3000, while the already elevated level of resistance against DC3000 ΔaprA remained unchanged. Together, these results indicate that evasion of host immunity by the alkaline protease AprA is important for full virulence of strain DC3000 and likely acts by preventing flagellin monomers from being recognized by its cognate immune receptor.

  14. Comparison of worm development and host immune responses in natural hosts of schistosoma japonicum, yellow cattle and water buffalo

    Directory of Open Access Journals (Sweden)

    Yang Jianmei

    2012-03-01

    Full Text Available Abstract Background Yellow cattle and water buffalo are two of the most important natural hosts for Schistosoma japonicum in China. Previous observation has revealed that yellow cattle are more suited to the development of S. japonicum than water buffalo. Understanding more about the molecular mechanisms involved in worm development, as well as the pathological and immunological differences between yellow cattle and water buffalo post infection with S japonicum will provide useful information for the vaccine design and its delivery procedure. Results The worm length (p p p + T cells was higher in yellow cattle, while the percentage of CD8+ T cells was higher in water buffalo from pre-infection to 7 w post infection. The CD4/CD8 ratios were decreased in both species after challenge with schistosomes. Comparing with water buffalo, the IFN-γ level was higher and decreased significantly, while the IL-4 level was lower and increased gradually in yellow cattle from pre-infection to 7 w post infection. Conclusions In this study, we confirmed that yellow cattle were more suited to the development of S. japonicum than water buffalo, and more serious pathological damage was observed in infected yellow cattle. Immunological analysis suggested that CD4+ T cells might be an integral component of the immune response and might associate with worm development in yellow cattle. A shift from Th1 to Th2 type polarized immunity was only shown clearly in schistosome-infected yellow cattle, but no shift in water buffalo. The results provide valuable information for increased understanding of host-schistosome interactions, and for control of schistosomiasis.

  15. Zinc Homeostasis at the Bacteria/Host Interface-From Coordination Chemistry to Nutritional Immunity.

    Science.gov (United States)

    Wątły, Joanna; Potocki, Sławomir; Rowińska-Żyrek, Magdalena

    2016-11-02

    Zinc is one of the most important metal nutrients for species from all kingdoms, being a key structural or catalytic component of hundreds of enzymes, crucial for the survival of both pathogenic microorganisms and their hosts. This work is an overview of the homeostasis of zinc in bacteria and humans. It explains the importance of this metal nutrient for pathogens, describes the roles of zinc sensors, regulators, and transporters, and summarizes various uptake systems and different proteins involved in zinc homeostasis-both those used for storage, buffering, and signaling inside the cell and those excreted in order to obtain Zn II from the host. The human zinc-dependent immune system response is explained, with a special focus given to 'zinc nutritional immunity', a process that describes the competition between the bacteria or fungus and the host for this metal, during which both the pathogen and host make huge efforts to control zinc availability. This sophisticated tug of war over Zn II might be considered as a possible target for novel antibacterial therapies. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Bacterial immunostat: Mycobacterium tuberculosis lipids and their role in the host immune response

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    Adriano Queiroz

    Full Text Available Abstract: The lipid-rich cell wall of Mycobacterium tuberculosis is a dynamic structure that is involved in the regulation of the transport of nutrients, toxic host-cell effector molecules, and anti-tuberculosis drugs. It is therefore postulated to contribute to the long-term bacterial survival in an infected human host. Accumulating evidence suggests that M. tuberculosis remodels the lipid composition of the cell wall as an adaptive mechanism against host-imposed stress. Some of these lipid species (trehalose dimycolate, diacylated sulphoglycolipid, and mannan-based lipoglycans trigger an immunopathologic response, whereas others (phthiocerol dimycocerosate, mycolic acids, sulpholipid-1, and di-and polyacyltrehalose appear to dampen the immune responses. These lipids appear to be coordinately expressed in the cell wall of M. tuberculosis during different phases of infection, ultimately determining the clinical fate of the infection. This review summarizes the current state of knowledge on the metabolism, transport, and homeostatic or immunostatic regulation of the cell wall lipids, and their orchestrated interaction with host immune responses that results in bacterial clearance, persistence, or tuberculosis.

  17. Bifidobacterial surface-exopolysaccharide facilitates commensal-host interaction through immune modulation and pathogen protection

    Science.gov (United States)

    Fanning, Saranna; Hall, Lindsay J.; Cronin, Michelle; Zomer, Aldert; MacSharry, John; Goulding, David; O'Connell Motherway, Mary; Shanahan, Fergus; Nally, Kenneth; Dougan, Gordon; van Sinderen, Douwe

    2012-01-01

    Bifidobacteria comprise a significant proportion of the human gut microbiota. Several bifidobacterial strains are currently used as therapeutic interventions, claiming various health benefits by acting as probiotics. However, the precise mechanisms by which they maintain habitation within their host and consequently provide these benefits are not fully understood. Here we show that Bifidobacterium breve UCC2003 produces a cell surface-associated exopolysaccharide (EPS), the biosynthesis of which is directed by either half of a bidirectional gene cluster, thus leading to production of one of two possible EPSs. Alternate transcription of the two opposing halves of this cluster appears to be the result of promoter reorientation. Surface EPS provided stress tolerance and promoted in vivo persistence, but not initial colonization. Marked differences were observed in host immune response: strains producing surface EPS (EPS+) failed to elicit a strong immune response compared with EPS-deficient variants. Specifically, EPS production was shown to be linked to the evasion of adaptive B-cell responses. Furthermore, presence of EPS+ B. breve reduced colonization levels of the gut pathogen Citrobacter rodentium. Our data thus assigns a pivotal and beneficial role for EPS in modulating various aspects of bifidobacterial–host interaction, including the ability of commensal bacteria to remain immunologically silent and in turn provide pathogen protection. This finding enforces the probiotic concept and provides mechanistic insights into health-promoting benefits for both animal and human hosts. PMID:22308390

  18. Understanding regulation of the host-mediated gut symbiont population and the symbiont-mediated host immunity in the Riptortus-Burkholderia symbiosis system.

    Science.gov (United States)

    Kim, Jiyeun Kate; Lee, Jun Beom; Jang, Ho Am; Han, Yeon Soo; Fukatsu, Takema; Lee, Bok Luel

    2016-11-01

    Valuable insect models have tremendously contributed to our understanding of innate immunity and symbiosis. Bean bug, Riptortus pedestris, is a useful insect symbiosis model due to harboring cultivable monospecific gut symbiont, genus Burkholderia. Bean bug is a hemimetabolous insect whose immunity is not well-understood. However, we recently identified three major antimicrobial peptides of Riptortus and examined the relationship between gut symbiosis and host immunity. We found that the presence of Burkholderia gut symbiont positively affects Riptortus immunity. From studying host regulation mechanisms of symbiont population, we revealed that the symbiotic Burkholderia cells are much more susceptible to Riptortus immune responses than the cultured cells. We further elucidated that the immune-susceptibility of the Burkholderia gut symbionts is due to the drastic change of bacterial cell envelope. Finally, we show that the immune-susceptible Burkholderia symbionts are able to prosper in host owing to the suppression of immune responses of the symbiotic midgut. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Dual RNA-seq reveals no plastic transcriptional response of the coccidian parasite Eimeria falciformis to host immune defenses.

    Science.gov (United States)

    Ehret, Totta; Spork, Simone; Dieterich, Christoph; Lucius, Richard; Heitlinger, Emanuel

    2017-09-05

    Parasites can either respond to differences in immune defenses that exist between individual hosts plastically or, alternatively, follow a genetically canalized ("hard wired") program of infection. Assuming that large-scale functional plasticity would be discernible in the parasite transcriptome we have performed a dual RNA-seq study of the lifecycle of Eimeria falciformis using infected mice with different immune status as models for coccidian infections. We compared parasite and host transcriptomes (dual transcriptome) between naïve and challenge infected mice, as well as between immune competent and immune deficient ones. Mice with different immune competence show transcriptional differences as well as differences in parasite reproduction (oocyst shedding). Broad gene categories represented by differently abundant host genes indicate enrichments for immune reaction and tissue repair functions. More specifically, TGF-beta, EGF, TNF and IL-1 and IL-6 are examples of functional annotations represented differently depending on host immune status. Much in contrast, parasite transcriptomes were neither different between Coccidia isolated from immune competent and immune deficient mice, nor between those harvested from naïve and challenge infected mice. Instead, parasite transcriptomes have distinct profiles early and late in infection, characterized largely by biosynthesis or motility associated functional gene groups, respectively. Extracellular sporozoite and oocyst stages showed distinct transcriptional profiles and sporozoite transcriptomes were found enriched for species specific genes and likely pathogenicity factors. We propose that the niche and host-specific parasite E. falciformis uses a genetically canalized program of infection. This program is likely fixed in an evolutionary process rather than employing phenotypic plasticity to interact with its host. This in turn might limit the potential of the parasite to adapt to new host species or niches, forcing

  20. Interactions between host metabolism, immune regulation, and the gut microbiota in diet-associated obesity and metabolic dysfunction

    DEFF Research Database (Denmark)

    Andersen, Daniel

    The increase in the prevalence of obesity and obesity-associated complications such as the metabolic syndrome is becoming a global challenge. Dietary habits and nutrient consumption modulates host homeostasis, which manifests in various diet-induced complications marked by changes in host...... metabolism and immune regulation, which are intricately linked. In addition, diet effectively shapes the gut microbiota composition and activity, which in turn interacts with the host to modulate host metabolism and immune regulation. In the three studies included in this PhD thesis, we have explored...... the impact of specific dietary components on host metabolic function, immune regulation and gut microbiota composition and activity. In the first study, we have characterized the effect of a combined high-fat and gliadin-rich diet, since dietary gliadin has been reported to be associated with intestinal...

  1. Impact of Nosema ceranae and Nosema apis on individual worker bees of the two host species (Apis cerana and Apis mellifera) and regulation of host immune response.

    Science.gov (United States)

    Sinpoo, Chainarong; Paxton, Robert J; Disayathanoowat, Terd; Krongdang, Sasiprapa; Chantawannakul, Panuwan

    Nosema apis and Nosema ceranae are obligate intracellular microsporidian parasites infecting midgut epithelial cells of host adult honey bees, originally Apis mellifera and Apis cerana respectively. Each microsporidia cross-infects the other host and both microsporidia nowadays have a worldwide distribution. In this study, cross-infection experiments using both N. apis and N. ceranae in both A. mellifera and A. cerana were carried out to compare pathogen proliferation and impact on hosts, including host immune response. Infection by N. ceranae led to higher spore loads than by N. apis in both host species, and there was greater proliferation of microsporidia in A. mellifera compared to A. cerana. Both N. apis and N. ceranae were pathogenic in both host Apis species. N. ceranae induced subtly, though not significantly, higher mortality than N. apis in both host species, yet survival of A. cerana was no different to that of A. mellifera in response to N. apis or N. ceranae. Infections of both host species with N. apis and N. ceranae caused significant up-regulation of AMP genes and cellular mediated immune genes but did not greatly alter apoptosis-related gene expression. In this study, A. cerana enlisted a higher immune response and displayed lower loads of N. apis and N. ceranae spores than A. mellifera, suggesting it may be better able to defend itself against microsporidia infection. We caution against over-interpretation of our results, though, because differences between host and parasite species in survival were insignificant and because size differences between microsporidia species and between host Apis species may alternatively explain the differential proliferation of N. ceranae in A. mellifera. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Host Immunization with Recombinant Proteins to Screen Antigens for Tick Control.

    Science.gov (United States)

    Galay, Remil Linggatong; Miyata, Takeshi; Umemiya-Shirafuji, Rika; Mochizuki, Masami; Fujisaki, Kozo; Tanaka, Tetsuya

    2016-01-01

    Ticks (Parasitiformes: Ixodida) are known for their obligate blood feeding habit and their role in transmitting pathogens to various vertebrate hosts. Tick control using chemical acaricides is extensively used particularly in livestock management, but several disadvantages arise from resistance development of many tick species, and concerns on animal product and environmental contamination. Vaccination offers better protection and more cost-effective alternative to application of chemical acaricides, addressing their disadvantages. However, an ideal anti-tick vaccine targeting multiple tick species and all the tick stages is still wanting. Here, we describe the procedures involved in the evaluation of a vaccine candidate antigen against ticks at the laboratory level, from the preparation of recombinant proteins, administration to the rabbit host and monitoring of antibody titer, to tick infestation challenge and determination of the effects of immunization to ticks.

  3. Plant Hormone Salicylic Acid Produced by a Malaria Parasite Controls Host Immunity and Cerebral Malaria Outcome.

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    Ryuma Matsubara

    Full Text Available The apicomplexan parasite Toxoplasma gondii produces the plant hormone abscisic acid, but it is unclear if phytohormones are produced by the malaria parasite Plasmodium spp., the most important parasite of this phylum. Here, we report detection of salicylic acid, an immune-related phytohormone of land plants, in P. berghei ANKA and T. gondii cell lysates. However, addition of salicylic acid to P. falciparum and T. gondii culture had no effect. We transfected P. falciparum 3D7 with the nahG gene, which encodes a salicylic acid-degrading enzyme isolated from plant-infecting Pseudomonas sp., and established a salicylic acid-deficient mutant. The mutant had a significantly decreased concentration of parasite-synthesized prostaglandin E2, which potentially modulates host immunity as an adaptive evolution of Plasmodium spp. To investigate the function of salicylic acid and prostaglandin E2 on host immunity, we established P. berghei ANKA mutants expressing nahG. C57BL/6 mice infected with nahG transfectants developed enhanced cerebral malaria, as assessed by Evans blue leakage and brain histological observation. The nahG-transfectant also significantly increased the mortality rate of mice. Prostaglandin E2 reduced the brain symptoms by induction of T helper-2 cytokines. As expected, T helper-1 cytokines including interferon-γ and interleukin-2 were significantly elevated by infection with the nahG transfectant. Thus, salicylic acid of Plasmodium spp. may be a new pathogenic factor of this threatening parasite and may modulate immune function via parasite-produced prostaglandin E2.

  4. Analyses of Brucella pathogenesis, host immunity, and vaccine targets using systems biology and bioinformatics

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    Yongqun eHe

    2012-02-01

    Full Text Available Brucella is a Gram-negative, facultative intracellular bacterium that causes zoonotic brucellosis in humans and various animals. Out of ten classified Brucella species, B. melitensis, B. abortus, B. suis, and B. canis are pathogenic to humans. In the past decade, the mechanisms of Brucella pathogenesis and host immunity have been extensively investigated using the cutting edge systems biology and bioinformatics approaches. This article provides a comprehensive review of the applications of Omics (including genomics, transcriptomics, and proteomics and bioinformatics technologies for the analysis of Brucella pathogenesis, host immune responses, and vaccine targets. Based on more than 30 sequenced Brucella genomes, comparative genomics is able to identify gene variations among Brucella strains that help to explain host specificity and virulence differences among Brucella species. Diverse transcriptomics and proteomics gene expression studies have been conducted to analyze gene expression profiles of wild type Brucella strains and mutants under different laboratory conditions. High throughput Omics analyses of host responses to infections with virulent or attenuated Brucella strains have been focused on responses by mouse and cattle macrophages, bovine trophoblastic cells, mouse and boar splenocytes, and ram buffy coat. Differential serum responses in humans and rams to Brucella infections have been analyzed using high throughput serum antibody screening technology. The Vaxign reverse vaccinology has been used to predict many Brucella vaccine targets. More than 180 Brucella virulence factors and their gene interaction networks have been identified using advanced literature mining methods. The recent development of community-based Vaccine Ontology and Brucellosis Ontology provides an efficient way for Brucella data integration, exchange, and computer-assisted automated reasoning.

  5. Analyses of Brucella Pathogenesis, Host Immunity, and Vaccine Targets using Systems Biology and Bioinformatics

    Science.gov (United States)

    He, Yongqun

    2011-01-01

    Brucella is a Gram-negative, facultative intracellular bacterium that causes zoonotic brucellosis in humans and various animals. Out of 10 classified Brucella species, B. melitensis, B. abortus, B. suis, and B. canis are pathogenic to humans. In the past decade, the mechanisms of Brucella pathogenesis and host immunity have been extensively investigated using the cutting edge systems biology and bioinformatics approaches. This article provides a comprehensive review of the applications of Omics (including genomics, transcriptomics, and proteomics) and bioinformatics technologies for the analysis of Brucella pathogenesis, host immune responses, and vaccine targets. Based on more than 30 sequenced Brucella genomes, comparative genomics is able to identify gene variations among Brucella strains that help to explain host specificity and virulence differences among Brucella species. Diverse transcriptomics and proteomics gene expression studies have been conducted to analyze gene expression profiles of wild type Brucella strains and mutants under different laboratory conditions. High throughput Omics analyses of host responses to infections with virulent or attenuated Brucella strains have been focused on responses by mouse and cattle macrophages, bovine trophoblastic cells, mouse and boar splenocytes, and ram buffy coat. Differential serum responses in humans and rams to Brucella infections have been analyzed using high throughput serum antibody screening technology. The Vaxign reverse vaccinology has been used to predict many Brucella vaccine targets. More than 180 Brucella virulence factors and their gene interaction networks have been identified using advanced literature mining methods. The recent development of community-based Vaccine Ontology and Brucellosis Ontology provides an efficient way for Brucella data integration, exchange, and computer-assisted automated reasoning. PMID:22919594

  6. Invasion of Dendritic Cells, Macrophages and Neutrophils by the Bordetella Adenylate Cyclase Toxin: A Subversive Move to Fool Host Immunity.

    Science.gov (United States)

    Fedele, Giorgio; Schiavoni, Ilaria; Adkins, Irena; Klimova, Nela; Sebo, Peter

    2017-09-21

    Adenylate cyclase toxin (CyaA) is released in the course of B. pertussis infection in the host's respiratory tract in order to suppress its early innate and subsequent adaptive immune defense. CD11b-expressing dendritic cells (DC), macrophages and neutrophils are professional phagocytes and key players of the innate immune system that provide a first line of defense against invading pathogens. Recent findings revealed the capacity of B. pertussis CyaA to intoxicate DC with high concentrations of 3',5'-cyclic adenosine monophosphate (cAMP), which ultimately skews the host immune response towards the expansion of Th17 cells and regulatory T cells. CyaA-induced cAMP signaling swiftly incapacitates opsonophagocytosis, oxidative burst and NO-mediated killing of bacteria by neutrophils and macrophages. The subversion of host immune responses by CyaA after delivery into DC, macrophages and neutrophils is the subject of this review.

  7. Mycobacterium tuberculosis co-operonic PE32/PPE65 proteins alter host immune responses by hampering Th1 response

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    Mohd eKhubaib

    2016-05-01

    Full Text Available PE/PPE genes, present in cluster with ESAT-6 like genes, are suspected to have a role in antigenic variation and virulence of Mycobacterium tuberculosis. Their roles in immune evasion and immune modulation of host are also well documented. We present evidence that PE32/PPE65 present within the RD8 region are co-operonic, co-transcribed and co-translated, and play role in modulating host immune responses. Experiments with macrophage cell lines revealed that this protein complex suppresses pro-inflammatory cytokines such as TNF-α and IL-6 whereas also inducing high expression of anti-inflammatory IL-10. Immunization of mice with these recombinant proteins dampens an effective Th1 response as evident from reduced frequency of IFN-g and IL-2 producing CD4+ and CD8+ T cells. IgG sub-typing from serum of immunized mice revealed high levels of IgG1 when compared with IgG2a and IgG2b. Further IgG1/IgG2a ratio clearly demonstrated that the protein complex manipulates the host immune response favourable to the pathogen. Our results demonstrate that the co-transcribed and co-translated PE32 and PPE65 antigens are involved specifically in modulating anti-mycobacterial host immune response by hampering Th1 response.

  8. Rapamycin delays growth of Wnt-1 tumors in spite of suppression of host immunity

    International Nuclear Information System (INIS)

    Svirshchevskaya, Elena V; Mariotti, Jacopo; Wright, Mollie H; Viskova, Natalia Y; Telford, William; Fowler, Daniel H; Varticovski, Lyuba

    2008-01-01

    Rapamycin, an inhibitor of mammalian target of Rapamycin (mTOR), is an immunosuppressive agent that has anti-proliferative effects on some tumors. However, the role of Rapamycin-induced immune suppression on tumor progression has not been examined. We developed a transplantation model for generation of mammary tumors in syngeneic recipients that can be used to address the role of the immune system on tumor progression. We examined the effect of Rapamycin on the immune system and growth of MMTV-driven Wnt-1 mammary tumors which were transplanted into irradiated and bone marrow-reconstituted, or naïve mice. Rapamycin induced severe immunosuppression and significantly delayed the growth of Wnt-1 tumors. T cell depletion in spleen and thymus and reduction in T cell cytokine secretion were evident within 7 days of therapy. By day 20, splenic but not thymic T cell counts, and cytokine secretion recovered. We determined whether adoptive T cell therapy enhances the anti-cancer effect using ex vivo generated Rapamycin-resistant T cells. However, T cell transfer during Rapamycin therapy did not improve the outcome relative to drug therapy alone. Thus, we could not confirm that suppression of T cell immunity contributes to tumor growth in this model. Consistent with suppression of the mTOR pathway, decreased 4E-BP1, p70 S6-kinase, and S6 protein phosphorylation correlated with a decrease in Wnt-1 tumor cell proliferation. Rapamycin has a direct anti-tumor effect on Wnt-1 breast cancer in vivo that involves inhibition of the mTOR pathway at doses that also suppress host immune responses

  9. Rapid host immune response and viral dynamics in herpes simplex virus-2 infection

    Science.gov (United States)

    Schiffer, Joshua T; Corey, Lawrence

    2014-01-01

    Herpes Simplex Virus-2 (HSV-2) is episodically shed throughout the human genital tract. While high viral load correlates with development of genital ulcers, shedding also commonly occurs even when ulcers are not present, allowing for silent transmission during coitus and contributing to high seroprevalence of HSV-2 worldwide. Frequent viral reactivation occurs despite diverse and complementary host and viral mechanisms within ganglionic tissue that predispose towards latency, suggesting that viral replication may be constantly occurring in a small minority of neurons within the ganglia. Within genital mucosa, the in vivo expansion and clearance rates of HSV-2 are extremely rapid. Resident dendritic cells and memory HSV-specific T cells persist at prior sites of genital tract reactivation, and in conjunction with prompt innate recognition of infected cells, lead to rapid containment of infected cells. Shedding episodes vary greatly in duration and severity within a single person over time: this heterogeneity appears best explained by variation in the densities of host immunity across the genital tract. The fact that immune responses usually control viral replication in genital skin prior to development of lesions provides optimism that enhancing such responses could lead to effective vaccines and immunotherapies. PMID:23467247

  10. Demodex canis targets TLRs to evade host immunity and induce canine demodicosis.

    Science.gov (United States)

    Kumari, P; Nigam, R; Choudhury, S; Singh, S K; Yadav, B; Kumar, D; Garg, S K

    2018-03-01

    Widespread incidence of Demodex mites throughout the mammalian class and occasional serious and fatal outcomes in dogs warrant an insight into the host-parasite interface especially. Therefore, this study was aimed to unravel the interplay between innate immune response and canine demodicosis. The dogs diagnosed to have natural clinical demodicosis were allocated into two groups; dogs with localized demodicosis (LD) and with generalized demodicosis (GD). The expression of toll-like receptors (TLRs) 2, 4 and 6 genes in peripheral blood mononuclear cells of these dogs was quantified by real-time PCR. Significantly increased TLR2 gene expression, while significantly diminished TLR4 and TLR6 gene expressions were observed in demodicosed dogs (LD and GD) as compared with the healthy ones. Even the expression of TLR2 gene was found to differ significantly between the dogs with LD and GD. Therefore, it can be inferred that clinical demodicosis in dogs is coupled with an up-regulation of TLR2 and down-regulation of TLR4 and TLR6 gene expressions. Overexpression of TLR2 gene might be responsible for Demodex-induced clinical manifestations, while TLR4 and TLR6 gene down-regulations could be the paramount strategy of Demodex mites to elude the host-immune interface. © 2017 John Wiley & Sons Ltd.

  11. Adenylate Cyclases of Trypanosoma brucei, Environmental Sensors and Controllers of Host Innate Immune Response.

    Science.gov (United States)

    Salmon, Didier

    2018-04-25

    Trypanosoma brucei , etiological agent of Sleeping Sickness in Africa, is the prototype of African trypanosomes, protozoan extracellular flagellate parasites transmitted by saliva ( Salivaria ). In these parasites the molecular controls of the cell cycle and environmental sensing are elaborate and concentrated at the flagellum. Genomic analyses suggest that these parasites appear to differ considerably from the host in signaling mechanisms, with the exception of receptor-type adenylate cyclases (AC) that are topologically similar to receptor-type guanylate cyclase (GC) of higher eukaryotes but control a new class of cAMP targets of unknown function, the cAMP response proteins (CARPs), rather than the classical protein kinase A cAMP effector (PKA). T. brucei possesses a large polymorphic family of ACs, mainly associated with the flagellar membrane, and these are involved in inhibition of the innate immune response of the host prior to the massive release of immunomodulatory factors at the first peak of parasitemia. Recent evidence suggests that in T. brucei several insect-specific AC isoforms are involved in social motility, whereas only a few AC isoforms are involved in cytokinesis control of bloodstream forms, attesting that a complex signaling pathway is required for environmental sensing. In this review, after a general update on cAMP signaling pathway and the multiple roles of cAMP, I summarize the existing knowledge of the mechanisms by which pathogenic microorganisms modulate cAMP levels to escape immune defense.

  12. Adenylate Cyclases of Trypanosoma brucei, Environmental Sensors and Controllers of Host Innate Immune Response

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    Didier Salmon

    2018-04-01

    Full Text Available Trypanosoma brucei, etiological agent of Sleeping Sickness in Africa, is the prototype of African trypanosomes, protozoan extracellular flagellate parasites transmitted by saliva (Salivaria. In these parasites the molecular controls of the cell cycle and environmental sensing are elaborate and concentrated at the flagellum. Genomic analyses suggest that these parasites appear to differ considerably from the host in signaling mechanisms, with the exception of receptor-type adenylate cyclases (AC that are topologically similar to receptor-type guanylate cyclase (GC of higher eukaryotes but control a new class of cAMP targets of unknown function, the cAMP response proteins (CARPs, rather than the classical protein kinase A cAMP effector (PKA. T. brucei possesses a large polymorphic family of ACs, mainly associated with the flagellar membrane, and these are involved in inhibition of the innate immune response of the host prior to the massive release of immunomodulatory factors at the first peak of parasitemia. Recent evidence suggests that in T. brucei several insect-specific AC isoforms are involved in social motility, whereas only a few AC isoforms are involved in cytokinesis control of bloodstream forms, attesting that a complex signaling pathway is required for environmental sensing. In this review, after a general update on cAMP signaling pathway and the multiple roles of cAMP, I summarize the existing knowledge of the mechanisms by which pathogenic microorganisms modulate cAMP levels to escape immune defense.

  13. Xenopus-FV3 host-pathogen interactions and immune evasion.

    Science.gov (United States)

    Jacques, Robert; Edholm, Eva-Stina; Jazz, Sanchez; Odalys, Torres-Luquis; Francisco, De Jesús Andino

    2017-11-01

    We first review fundamental insights into anti-ranavirus immunity learned with the Xenopus laevis/ranavirus FV3 model that are generally applicable to ectothermic vertebrates. We then further investigate FV3 genes involved in immune evasion. Focusing on FV3 knockout (KO) mutants defective for a putative viral caspase activation and recruitment domain-containing (CARD)-like protein (Δ64R-FV3), a β-hydroxysteroid dehydrogenase homolog (Δ52L-FV3), and an immediate-early18kDa protein (FV3-Δ18K), we assessed the involvement of these viral genes in replication, dissemination and interaction with peritoneal macrophages in tadpole and adult frogs. Our results substantiate the role of 64R and 52L as critical immune evasion genes, promoting persistence and dissemination in the host by counteracting type III IFN in tadpoles and type I IFN in adult frogs. Comparably, the substantial accumulation of genome copy numbers and exacerbation of type I and III IFN gene expression responses but deficient release of infectious virus suggests that 18K is a viral regulatory gene. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Host translational inhibition by Pseudomonas aeruginosa Exotoxin A Triggers an immune response in Caenorhabditis elegans.

    Science.gov (United States)

    McEwan, Deborah L; Kirienko, Natalia V; Ausubel, Frederick M

    2012-04-19

    Intestinal epithelial cells are exposed to both innocuous and pathogenic microbes, which need to be distinguished to mount an effective immune response. To understand the mechanisms underlying pathogen recognition, we investigated how Pseudomonas aeruginosa triggers intestinal innate immunity in Caenorhabditis elegans, a process independent of Toll-like pattern recognition receptors. We show that the P. aeruginosa translational inhibitor Exotoxin A (ToxA), which ribosylates elongation factor 2 (EF2), upregulates a significant subset of genes normally induced by P. aeruginosa. Moreover, immune pathways involving the ATF-7 and ZIP-2 transcription factors, which protect C. elegans from P. aeruginosa, are required for preventing ToxA-mediated lethality. ToxA-responsive genes are not induced by enzymatically inactive ToxA protein but can be upregulated independently of ToxA by disruption of host protein translation. Thus, C. elegans has a surveillance mechanism to recognize ToxA through its effect on protein translation rather than by direct recognition of either ToxA or ribosylated EF2. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Host immune response and acute disease in a zebrafish model of francisella pathogenesis

    Science.gov (United States)

    Vojtech, L.N.; Sanders, G.E.; Conway, C.; Ostland, V.; Hansen, J.D.

    2009-01-01

    Members of the bacterial genus Francisella are highly virulent and infectious pathogens. New models to study Francisella pathogenesis in evolutionarily distinct species are needed to provide comparative insight, as the mechanisms of host resistance and pathogen virulence are not well understood. We took advantage of the recent discovery of a novel species of Francisella to establish a zebrafish/Francisella comparative model of pathogenesis and host immune response. Adult zebraflsh were susceptible to acute Francisella-induced disease and suffered mortality in a dose-dependent manner. Using immunohistochemical analysis, we localized bacterial antigens primarily to lymphoid tissues and livers of zebraflsh following infection by intraperitoneal injection, which corresponded to regions of local cellular necrosis. Francisella sp. bacteria replicated rapidly in these tissues beginning 12 h postinfection, and bacterial titers rose steadily, leveled off, and then decreased by 7 days postinfection. Zebraflsh mounted a significant tissue-specific proinflammatory response to infection as measured by the upregulation of interleukin-l?? (IL-1??), gamma interferon, and tumor necrosis factor alpha mRNA beginning by 6 h postinfection and persisting for up to 7 days postinfection. In addition, exposure of zebraflsh to heat-killed bacteria demonstrated that the significant induction of IL-?? was highly specific to live bacteria. Taken together, the pathology and immune response to acute Francisella infection in zebraflsh share many features with those in mammals, highlighting the usefulness of this new model system for addressing both general and specific questions about Francisella host-pathogen interactions via an evolutionary approach. Copyright ?? 2009, American Society for Microbiology. All Rights Reserved.

  16. Expression of immune-response genes in lepidopteran host is suppressed by venom from an endoparasitoid, Pteromalus puparum

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    Fang Qi

    2010-09-01

    Full Text Available Abstract Background The relationships between parasitoids and their insect hosts have attracted attention at two levels. First, the basic biology of host-parasitoid interactions is of fundamental interest. Second, parasitoids are widely used as biological control agents in sustainable agricultural programs. Females of the gregarious endoparasitoid Pteromalus puparum (Hymenoptera: Pteromalidae inject venom along with eggs into their hosts. P. puparum does not inject polydnaviruses during oviposition. For this reason, P. puparum and its pupal host, the small white butterfly Pieris rapae (Lepidoptera: Pieridae, comprise an excellent model system for studying the influence of an endoparasitoid venom on the biology of the pupal host. P. puparum venom suppresses the immunity of its host, although the suppressive mechanisms are not fully understood. In this study, we tested our hypothesis that P. puparum venom influences host gene expression in the two main immunity-conferring tissues, hemocytes and fat body. Results At 1 h post-venom injection, we recorded significant decreases in transcript levels of 217 EST clones (revealing 113 genes identified in silico, including 62 unknown contigs derived from forward subtractive libraries of host hemocytes and in transcript levels of 288 EST clones (221 genes identified in silico, including 123 unknown contigs from libraries of host fat body. These genes are related to insect immune response, cytoskeleton, cell cycle and apoptosis, metabolism, transport, stress response and transcriptional and translational regulation. We verified the reliability of the suppression subtractive hybridization (SSH data with semi-quantitative RT-PCR analysis of a set of randomly selected genes. This analysis showed that most of the selected genes were down-regulated after venom injection. Conclusions Our findings support our hypothesis that P. puparum venom influences gene expression in host hemocytes and fat body. Specifically

  17. Nutrition and Helicobacter pylori: Host Diet and Nutritional Immunity Influence Bacterial Virulence and Disease Outcome

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    Kathryn P. Haley

    2016-01-01

    Full Text Available Helicobacter pylori colonizes the stomachs of greater than 50% of the world’s human population making it arguably one of the most successful bacterial pathogens. Chronic H. pylori colonization results in gastritis in nearly all patients; however in a subset of people, persistent infection with H. pylori is associated with an increased risk for more severe disease outcomes including B-cell lymphoma of mucosal-associated lymphoid tissue (MALT lymphoma and invasive adenocarcinoma. Research aimed at elucidating determinants that mediate disease progression has revealed genetic differences in both humans and H. pylori which increase the risk for developing gastric cancer. Furthermore, host diet and nutrition status have been shown to influence H. pylori-associated disease outcomes. In this review we will discuss how H. pylori is able to create a replicative niche within the hostile host environment by subverting and modifying the host-generated immune response as well as successfully competing for limited nutrients such as transition metals by deploying an arsenal of metal acquisition proteins and virulence factors. Lastly, we will discuss how micronutrient availability or alterations in the gastric microbiome may exacerbate negative disease outcomes associated with H. pylori colonization.

  18. Beneficial and Harmful Interactions of Antibiotics with Microbial Pathogens and the Host Innate Immune System

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    Ronald Anderson

    2010-05-01

    Full Text Available In general antibiotics interact cooperatively with host defences, weakening and decreasing the virulence of microbial pathogens, thereby increasing vulnerability to phagocytosis and eradication by the intrinsic antimicrobial systems of the host. Antibiotics, however, also interact with host defences by several other mechanisms, some harmful, others beneficial. Harmful activities include exacerbation of potentially damaging inflammatory responses, a property of cell-wall targeted agents, which promotes the release of pro-inflammatory microbial cytotoxins and cell-wall components. On the other hand, inhibitors of bacterial protein synthesis, especially macrolides, possess beneficial anti-inflammatory/cytoprotective activities, which result from interference with the production of microbial virulence factors/cytotoxins. In addition to these pathogen-directed, anti-inflammatory activities, some classes of antimicrobial agent possess secondary anti-inflammatory properties, unrelated to their conventional antimicrobial activities, which target cells of the innate immune system, particularly neutrophils. This is a relatively uncommon, potentially beneficial property of antibiotics, which has been described for macrolides, imidazole anti-mycotics, fluoroquinolones, and tetracyclines. Although of largely unproven significance in the clinical setting, increasing awareness of the pro-inflammatory and anti-inflammatory properties of antibiotics may contribute to a more discerning and effective use of these agents.

  19. Challenges and Strategies for Proteome Analysis of the Interaction of Human Pathogenic Fungi with Host Immune Cells.

    Science.gov (United States)

    Krüger, Thomas; Luo, Ting; Schmidt, Hella; Shopova, Iordana; Kniemeyer, Olaf

    2015-12-14

    Opportunistic human pathogenic fungi including the saprotrophic mold Aspergillus fumigatus and the human commensal Candida albicans can cause severe fungal infections in immunocompromised or critically ill patients. The first line of defense against opportunistic fungal pathogens is the innate immune system. Phagocytes such as macrophages, neutrophils and dendritic cells are an important pillar of the innate immune response and have evolved versatile defense strategies against microbial pathogens. On the other hand, human-pathogenic fungi have sophisticated virulence strategies to counteract the innate immune defense. In this context, proteomic approaches can provide deeper insights into the molecular mechanisms of the interaction of host immune cells with fungal pathogens. This is crucial for the identification of both diagnostic biomarkers for fungal infections and therapeutic targets. Studying host-fungal interactions at the protein level is a challenging endeavor, yet there are few studies that have been undertaken. This review draws attention to proteomic techniques and their application to fungal pathogens and to challenges, difficulties, and limitations that may arise in the course of simultaneous dual proteome analysis of host immune cells interacting with diverse morphotypes of fungal pathogens. On this basis, we discuss strategies to overcome these multifaceted experimental and analytical challenges including the viability of immune cells during co-cultivation, the increased and heterogeneous protein complexity of the host proteome dynamically interacting with the fungal proteome, and the demands on normalization strategies in terms of relative quantitative proteome analysis.

  20. Recent progress in host immunity to avian coccidiosis: IL-17 family cytokines as sentinels of the intestinal mucosa.

    Science.gov (United States)

    Min, Wongi; Kim, Woo H; Lillehoj, Erik P; Lillehoj, Hyun S

    2013-11-01

    The molecular and cellular mechanisms leading to immune protection against coccidiosis are complex and include multiple aspects of innate and adaptive immunities. Innate immunity is mediated by various subpopulations of immune cells that recognize pathogen associated molecular patterns (PAMPs) through their pattern recognition receptors (PRRs) leading to the secretion of soluble factors with diverse functions. Adaptive immunity, which is important in conferring protection against subsequent reinfections, involves subtypes of T and B lymphocytes that mediate antigen-specific immune responses. Recently, global gene expression microarray analysis has been used in an attempt to dissect this complex network of immune cells and molecules during avian coccidiosis. These new studies emphasized the uniqueness of the innate immune response to Eimeria infection, and directly led to the discovery of previously uncharacterized host genes and proteins whose expression levels were modulated following parasite infection. Among these is the IL-17 family of cytokines. This review highlights recent progress in IL-17 research in the context of host immunity to avian coccidiosis. Copyright © 2013. Published by Elsevier Ltd.

  1. IRAK-M regulation and function in host defense and immune homeostasis

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    Leah L.N. Hubbard

    2010-06-01

    Full Text Available Antigen presenting cells (APCs of the innate immune system sense a wide range of pathogens via pattern recognition receptors (PRRs. Engagement of certain PRRs can induce production of pro-inflammatory mediators that facilitate effective clearance of pathogen. Toll-like receptors (TLRs are a well described group of PRRs that belong to the TLR/Interleukin-1 receptor (IL-1R superfamily. However, TLR/IL-1R induction of pro-inflammatory mediators must be regulated to prevent excessive inflammation and tissue damage. One molecule of recent interest that is known to inhibit TLR/IL-1R signaling is interleukin-1 receptor associated kinase (IRAK-M, also known as IRAK-3. IRAK-M is expressed in a number of immune and epithelial cells types, and through its inhibition of pro-inflammatory cytokine production, IRAK-M can regulate immune homeostasis and tolerance in a number of infectious and non-infectious diseases. Furthermore, use of IRAK-M deficient animals has increased our understanding of the importance of IRAK-M in regulating immune responsiveness to a variety of pathogens. Although IRAK-M expression is typically induced through TLR signaling, IRAK-M can also be expressed in response to various endogenous and exogenous soluble factors as well as cell surface and intracellular signaling molecules. This review will focus on clinical scenarios in which expression of IRAK-M is beneficial (as in early sepsis and those situations where IRAK-M expression is harmful to the host (as in cancer and following bone marrow transplant. There is strong rationale for therapeutic targeting of IRAK-M for clinical benefit. However, effective targeting will require a greater understanding of the transcriptional regulation of this gene.

  2. Saccharomyces boulardii modifies Salmonella typhimurium traffic and host immune responses along the intestinal tract.

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    Rodolphe Pontier-Bres

    Full Text Available Salmonella enterica serovar Typhimurium (ST is an enteropathogenic Gram-negative bacterium that causes infection following oral ingestion. ST spreads rapidly along the gastrointestinal tract (GIT and invades the intestinal epithelium to ultimately reach internal body organs. The probiotic yeast Saccharomyces boulardii BIOCODEX (S.b-B is prescribed for prophylaxis of diarrheal infectious diseases. We previously showed that S.b-B prevents weight loss in ST-infected mice and significantly decreases bacterial translocation to the spleen and liver. This study was designed to investigate the effect of S.b-B on ST migration along the GIT and the impact of the yeast on the host's early innate immune responses. Bioluminescent imaging (BLI was used to evaluate the effect of S.b-B on the progression of luminescent Salmonella Typhimurium (ST-lux in the GIT of mice pretreated with streptomycin. Photonic emission (PE was measured in GIT extracts (stomach, small intestine, cecum and colon at various time periods post-infection (PI. PE analysis revealed that, 45 min PI, ST-lux had migrated slightly faster in the mice treated with S.b-B than in the untreated infected animals. At 90 min PI, ST-lux had reached the cecum in both groups of mice. Adhesion of ST to S.b-B was visualized in the intestines of the mice and probably accounts for (1 the faster elimination of ST-lux in the feces, and (2 reduced translocation of ST to the spleen and liver. In the early phase of infection, S.b-B also modifies the host's immune responses by (1 increasing IFN-γ gene expression and decreasing IL-10 gene expression in the small intestine, and (2 elevating both IFN-γ, and IL-10 mRNA levels in the cecum. BLI revealed that S.b-B modifies ST migration and the host immune response along the GIT. Study findings shed new light on the protective mechanisms of S.b-B during the early phase of Salmonella pathogenesis.

  3. Saccharomyces boulardii modifies Salmonella typhimurium traffic and host immune responses along the intestinal tract.

    Science.gov (United States)

    Pontier-Bres, Rodolphe; Munro, Patrick; Boyer, Laurent; Anty, Rodolphe; Imbert, Véronique; Terciolo, Chloé; André, Fréderic; Rampal, Patrick; Lemichez, Emmanuel; Peyron, Jean-François; Czerucka, Dorota

    2014-01-01

    Salmonella enterica serovar Typhimurium (ST) is an enteropathogenic Gram-negative bacterium that causes infection following oral ingestion. ST spreads rapidly along the gastrointestinal tract (GIT) and invades the intestinal epithelium to ultimately reach internal body organs. The probiotic yeast Saccharomyces boulardii BIOCODEX (S.b-B) is prescribed for prophylaxis of diarrheal infectious diseases. We previously showed that S.b-B prevents weight loss in ST-infected mice and significantly decreases bacterial translocation to the spleen and liver. This study was designed to investigate the effect of S.b-B on ST migration along the GIT and the impact of the yeast on the host's early innate immune responses. Bioluminescent imaging (BLI) was used to evaluate the effect of S.b-B on the progression of luminescent Salmonella Typhimurium (ST-lux) in the GIT of mice pretreated with streptomycin. Photonic emission (PE) was measured in GIT extracts (stomach, small intestine, cecum and colon) at various time periods post-infection (PI). PE analysis revealed that, 45 min PI, ST-lux had migrated slightly faster in the mice treated with S.b-B than in the untreated infected animals. At 90 min PI, ST-lux had reached the cecum in both groups of mice. Adhesion of ST to S.b-B was visualized in the intestines of the mice and probably accounts for (1) the faster elimination of ST-lux in the feces, and (2) reduced translocation of ST to the spleen and liver. In the early phase of infection, S.b-B also modifies the host's immune responses by (1) increasing IFN-γ gene expression and decreasing IL-10 gene expression in the small intestine, and (2) elevating both IFN-γ, and IL-10 mRNA levels in the cecum. BLI revealed that S.b-B modifies ST migration and the host immune response along the GIT. Study findings shed new light on the protective mechanisms of S.b-B during the early phase of Salmonella pathogenesis.

  4. Molecular basis of Trypanosoma cruzi and Leishmania interaction with their host(s): exploitation of immune and defense mechanisms by the parasite leading to persistence and chronicity, features reminiscent of immune system evasion strategies in cancer diseases.

    Science.gov (United States)

    Ouaissi, Ali; Ouaissi, Mehdi

    2005-01-01

    A number of features occurring during host-parasite interactions in Chagas disease caused by the protozoan parasite, Trypanosoma cruzi, and Leishmaniasis, caused by a group of kinetoplastid protozoan parasites are reminiscent of those observed in cancer diseases. In fact,although the cancer is not a single disease, and that T.cruzi and Leishmania are sophisticated eukaryotic parasites presenting a high level of genotypic variability the growth of the parasites in their host and that of cancer cells share at least one common feature, that is their mutual capacity for rapid cell division. Surprisingly, the parasitic diseases and cancers share some immune evasion strategies. Consideration of these immunological alterations must be added to the evaluation of the pathogenic processes. The molecular and functional characterization of virulence factors and the study of their effect on the arms of the immune system have greatly improved understanding of the regulation of immune effectors functions. The purpose of this review is to analyze some of the current data related to the regulatory components or processes originating from the parasite that control or interfere with host cell physiology. Attempts are also made to delineate some similarities between the immune evasion strategies that parasites and tumors employ. The elucidation of the mode of action of parasite virulence factors toward the host cell allow not only provide us with a more comprehensive view of the host-parasite relationships but may also represent a step forward in efforts aimed to identify new target molecules for therapeutic intervention.

  5. Invasion of Dendritic Cells, Macrophages and Neutrophils by the Bordetella Adenylate Cyclase Toxin: A Subversive Move to Fool Host Immunity

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    Giorgio Fedele

    2017-09-01

    Full Text Available Adenylate cyclase toxin (CyaA is released in the course of B. pertussis infection in the host’s respiratory tract in order to suppress its early innate and subsequent adaptive immune defense. CD11b-expressing dendritic cells (DC, macrophages and neutrophils are professional phagocytes and key players of the innate immune system that provide a first line of defense against invading pathogens. Recent findings revealed the capacity of B. pertussis CyaA to intoxicate DC with high concentrations of 3′,5′-cyclic adenosine monophosphate (cAMP, which ultimately skews the host immune response towards the expansion of Th17 cells and regulatory T cells. CyaA-induced cAMP signaling swiftly incapacitates opsonophagocytosis, oxidative burst and NO-mediated killing of bacteria by neutrophils and macrophages. The subversion of host immune responses by CyaA after delivery into DC, macrophages and neutrophils is the subject of this review.

  6. Ficolins do not alter host immune responses to lipopolysaccharide-induced inflammation in vivo

    DEFF Research Database (Denmark)

    Genster, Ninette; Østrup, Olga; Schjalm, Camilla

    2017-01-01

    . Yet, the contribution of ficolins to inflammatory disease processes remains elusive. To address this, we investigated ficolin deficient mice during a lipopolysaccharide (LPS)-induced model of systemic inflammation. Although murine serum ficolin was shown to bind LPS in vitro, there was no difference...... an unaltered spleen transcriptome profile in ficolin deficient mice compared to wildtype mice. Collectively, results from this study demonstrate that ficolins are not involved in host response to LPS-induced systemic inflammation.......Ficolins are a family of pattern recognition molecules that are capable of activating the lectin pathway of complement. A limited number of reports have demonstrated a protective role of ficolins in animal models of infection. In addition, an immune modulatory role of ficolins has been suggested...

  7. Postoperative radiation therapy and adjuvant chemoimmunotherapy in breast cancer. Aspects of timing and immune competence

    Energy Technology Data Exchange (ETDEWEB)

    Klefstroem, P.; Nuortio, L.; Taskinen, E.

    The effects of radiation therapy and adjuvant chemoimmunotherapy on the immune competence of patients with breast cancer were investigated. The tests performed included intradermal tuberculin tests, T- and B-lymphocyte counts, and lymphocyte blast transformation tests; phytohemagglutinin (PHA), concanavalin A (ConA) and pokeweed mitogen (PMW) were used as mitogens. Enhancement in lymphocyte proliferative response to mitogenic stimulation by PHA and PMW was seen in patients after 3 courses of chemotherapy + levamisole, whereas irradiation given after chemotherapy caused long-lasting depression in response to PHA and PWM (not significant). T-lymphocyte counts were also lower after irradiation than after chemoimmunotherapy. Clinically, the 16 patients treated with radiation therapy after chemotherapy exhibited a higher recurrence rate than the 24 patients treated first by irradiation. Enhanced reactivity to tuberculin tests occurred generally in patients receiving a planned treatment including irradiation, chemotherapy (5-fluorouracil, doxorubicin, cyclophosphamide) and levamisole. Enhancement of reactivity was seen more often in patients who had not relapsed.

  8. The Ustilago maydis effector Pep1 suppresses plant immunity by inhibition of host peroxidase activity.

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    Christoph Hemetsberger

    Full Text Available The corn smut Ustilago maydis establishes a biotrophic interaction with its host plant maize. This interaction requires efficient suppression of plant immune responses, which is attributed to secreted effector proteins. Previously we identified Pep1 (Protein essential during penetration-1 as a secreted effector with an essential role for U. maydis virulence. pep1 deletion mutants induce strong defense responses leading to an early block in pathogenic development of the fungus. Using cytological and functional assays we show that Pep1 functions as an inhibitor of plant peroxidases. At sites of Δpep1 mutant penetrations, H₂O₂ strongly accumulated in the cell walls, coinciding with a transcriptional induction of the secreted maize peroxidase POX12. Pep1 protein effectively inhibited the peroxidase driven oxidative burst and thereby suppresses the early immune responses of maize. Moreover, Pep1 directly inhibits peroxidases in vitro in a concentration-dependent manner. Using fluorescence complementation assays, we observed a direct interaction of Pep1 and the maize peroxidase POX12 in vivo. Functional relevance of this interaction was demonstrated by partial complementation of the Δpep1 mutant defect by virus induced gene silencing of maize POX12. We conclude that Pep1 acts as a potent suppressor of early plant defenses by inhibition of peroxidase activity. Thus, it represents a novel strategy for establishing a biotrophic interaction.

  9. HSV-1 ICP0: An E3 Ubiquitin Ligase That Counteracts Host Intrinsic and Innate Immunity

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    Mirna Perusina Lanfranca

    2014-05-01

    Full Text Available The herpes simplex virus type 1 (HSV-1 encoded E3 ubiquitin ligase, infected cell protein 0 (ICP0, is required for efficient lytic viral replication and regulates the switch between the lytic and latent states of HSV-1. As an E3 ubiquitin ligase, ICP0 directs the proteasomal degradation of several cellular targets, allowing the virus to counteract different cellular intrinsic and innate immune responses. In this review, we will focus on how ICP0’s E3 ubiquitin ligase activity inactivates the host intrinsic defenses, such as nuclear domain 10 (ND10, SUMO, and the DNA damage response to HSV-1 infection. In addition, we will examine ICP0’s capacity to impair the activation of interferon (innate regulatory mediators that include IFI16 (IFN γ-inducible protein 16, MyD88 (myeloid differentiation factor 88, and Mal (MyD88 adaptor-like protein. We will also consider how ICP0 allows HSV-1 to evade activation of the NF-κB (nuclear factor kappa B inflammatory signaling pathway. Finally, ICP0’s paradoxical relationship with USP7 (ubiquitin specific protease 7 and its roles in intrinsic and innate immune responses to HSV-1 infection will be discussed.

  10. Characterization and monitoring of host immune responses to infectious agents: what a future for microbiological diagnostics?

    Directory of Open Access Journals (Sweden)

    Riccardo Dolcetti

    2009-06-01

    Full Text Available Our knowledge on the mechanisms underlying microbial pathogenesis and host-microbe interactions has greatly improved over the last decade. In particular, the development of new and specific analytical methods has allowed the detailed characterization of innate and adaptive immune responses against clinically relevant microbial infections. Immunogenetic studies are continuously providing new insights on the genetic bases of individual differences in susceptibility to specific pathogens and most of the genetic markers identified so far include polymorphisms in genes controlling both innate and adaptive immune responses. Moreover, new standardized T cell assays allow reliable and reproducible evaluations of T cell phenotype and functions (i.e.: ELISPOT, including the identification of distinct functional signatures that are associated with the control of the infection.Although the number of these assays currently used in clinical practice is limited, a considerable increase is foreseen for the near future.This perspective constitutes an unprecedented opportunity for Clinical Microbiologists, who may now develop and apply integrated microbiologic/immunologic assays that may be useful for a more precise diagnostic definition and a more accurate clinical monitoring of the disease.

  11. Insecticidal activity of the metalloprotease AprA occurs through suppression of host cellular and humoral immunity.

    Science.gov (United States)

    Lee, Seung Ah; Jang, Seong Han; Kim, Byung Hyun; Shibata, Toshio; Yoo, Jinwook; Jung, Yunjin; Kawabata, Shun-Ichiro; Lee, Bok Luel

    2018-04-01

    The biochemical characterization of virulence factors from entomopathogenic bacteria is important to understand entomopathogen-insect molecular interactions. Pseudomonas entomophila is a typical entomopathogenic bacterium that harbors virulence factors against several insects. However, the molecular actions of these factors against host innate immune responses are not clearly elucidated. In this study, we observed that bean bugs (Riptortus pedestris) that were injected with P. entomophila were highly susceptible to this bacterium. To determine how P. entomophila counteracts the host innate immunity to survive within the insect, we purified a highly enriched protein with potential host insect-killing activity from the culture supernatant of P. entomophila. Then, a 45-kDa protein was purified to homogeneity and identified as AprA which is an alkaline zinc metalloprotease of the genus Pseudomonas by liquid chromatography mass spectrometry (LC-MS). Purified AprA showed a pronounced killing effect against host insects and suppressed both host cellular and humoral innate immunity. Furthermore, to show that AprA is an important insecticidal protein of P. entomophila, we used an aprA-deficient P. entomophila mutant strain (ΔaprA). When ΔaprA mutant cells were injected to host insects, this mutant exhibited extremely attenuated virulence. In addition, the cytotoxicity against host hemocytes and the antimicrobial peptide-degrading ability of the ΔaprA mutant were greatly decreased. These findings suggest that AprA functions as an important insecticidal protein of P. entomophila via suppression of host cellular and humoral innate immune responses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. THE BIOTIC FACTOR OF TREMATOD OPISTHORHIS FELINEUS INVASION INFLUENCE ON HOST IMMUNE STATUS AND SOMATIC CELLS PROLIFERATIVE ACTIVITY

    Directory of Open Access Journals (Sweden)

    A. G. Rybka

    2016-01-01

    Full Text Available The paper confirms long-time opisthorhis invasion role as a risk factor of host immune system reconstitution as well as an important factor in holangiocarcinomas development. It was shown that opisthorhosis invasion primal stage induce host immune system reconstitution. Host immune B-cells system is activated by metacercaria antigens, while the same antigens inhibits T-cells activity. Opisthorhis metabolites stimulate proliferative mithogen-induced T-cells acti vity. Chronic opisthorchis invasion leads to immune system disbalance. It means: decrease of specific and non-speci fic natural killers activity, number of high proliferative activity T-lymphocytes and the shift of regulatory T-cells subset to suppressors prevalence. At the same time specific as well as non-specific T-suppressors functional ability is very low. It was shown T-cells helper-amplifier activation. Despite of circulating B-cells decrease the antibody produced cells number is spleen increases significantly at the same time with circulating immune complexes accumulation. Even 3–6 month after dehelmintisation the immune system disbalance decreases but lefts. In addition, chronic opisthorhis invasion leads to the proliferative processes activation in ductal epithelium, liver, lymph nodes and in other organs which leads to cancer proliferation. According to the results obtained the opisthorhis infected patients needs to be immunocorrected before as well as after dehelmintisation for holangiocancerogenesis profylaxis.

  13. Filarial parasites develop faster and reproduce earlier in response to host immune effectors that determine filarial life expectancy.

    Science.gov (United States)

    Babayan, Simon A; Read, Andrew F; Lawrence, Rachel A; Bain, Odile; Allen, Judith E

    2010-10-19

    Humans and other mammals mount vigorous immune assaults against helminth parasites, yet there are intriguing reports that the immune response can enhance rather than impair parasite development. It has been hypothesized that helminths, like many free-living organisms, should optimize their development and reproduction in response to cues predicting future life expectancy. However, immune-dependent development by helminth parasites has so far eluded such evolutionary explanation. By manipulating various arms of the immune response of experimental hosts, we show that filarial nematodes, the parasites responsible for debilitating diseases in humans like river blindness and elephantiasis, accelerate their development in response to the IL-5 driven eosinophilia they encounter when infecting a host. Consequently they produce microfilariae, their transmission stages, earlier and in greater numbers. Eosinophilia is a primary host determinant of filarial life expectancy, operating both at larval and at late adult stages in anatomically and temporally separate locations, and is implicated in vaccine-mediated protection. Filarial nematodes are therefore able to adjust their reproductive schedules in response to an environmental predictor of their probability of survival, as proposed by evolutionary theory, thereby mitigating the effects of the immune attack to which helminths are most susceptible. Enhancing protective immunity against filarial nematodes, for example through vaccination, may be less effective at reducing transmission than would be expected and may, at worst, lead to increased transmission and, hence, pathology.

  14. Filarial parasites develop faster and reproduce earlier in response to host immune effectors that determine filarial life expectancy.

    Directory of Open Access Journals (Sweden)

    Simon A Babayan

    Full Text Available Humans and other mammals mount vigorous immune assaults against helminth parasites, yet there are intriguing reports that the immune response can enhance rather than impair parasite development. It has been hypothesized that helminths, like many free-living organisms, should optimize their development and reproduction in response to cues predicting future life expectancy. However, immune-dependent development by helminth parasites has so far eluded such evolutionary explanation. By manipulating various arms of the immune response of experimental hosts, we show that filarial nematodes, the parasites responsible for debilitating diseases in humans like river blindness and elephantiasis, accelerate their development in response to the IL-5 driven eosinophilia they encounter when infecting a host. Consequently they produce microfilariae, their transmission stages, earlier and in greater numbers. Eosinophilia is a primary host determinant of filarial life expectancy, operating both at larval and at late adult stages in anatomically and temporally separate locations, and is implicated in vaccine-mediated protection. Filarial nematodes are therefore able to adjust their reproductive schedules in response to an environmental predictor of their probability of survival, as proposed by evolutionary theory, thereby mitigating the effects of the immune attack to which helminths are most susceptible. Enhancing protective immunity against filarial nematodes, for example through vaccination, may be less effective at reducing transmission than would be expected and may, at worst, lead to increased transmission and, hence, pathology.

  15. Infective Larvae of Brugia malayi Induce Polarization of Host Macrophages that Helps in Immune Evasion

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    Aditi Sharma

    2018-02-01

    Full Text Available Filarial parasites suppress, divert, or polarize the host immune response to aid their survival. However, mechanisms that govern the polarization of host MΦs during early filarial infection are not completely understood. In this study, we infected BALB/c mice with infective larvae stage-3 of Brugia malayi (Bm-L3 and studied their effect on the polarization of splenic MΦs. Results showed that MΦs displayed M2-phenotype by day 3 p.i. characterized by upregulated IL-4, but reduced IL-12 and Prostaglandin-D2 secretion. Increased arginase activity, higher arginase-1 but reduced NOS2 expression and poor phagocytic and antigen processing capacity was also observed. M2 MΦs supported T-cell proliferation and characteristically upregulated p-ERK but downregulated NF-κB-p65 and NF-κB-p50/105. Notably, Bm-L3 synergized with host regulatory T-cells (Tregs and polarized M2 MΦs to regulatory MΦs (Mregs by day 7 p.i., which secreted copious amounts of IL-10 and prostaglandin-E2. Mregs also showed upregulated expression levels of MHC-II, CD80, and CD86 and exhibited increased antigen-processing capacity but displayed impaired activation of NF-κB-p65 and NF-κB-p50/105. Neutralization of Tregs by anti-GITR + anti-CD25 antibodies checked the polarization of M2 MΦs to Mregs, decreased accumulation of regulatory B cells and inflammatory monocytes, and reduced secretion of IL-10, but enhanced IL-4 production and percentages of eosinophils, which led to Bm-L3 killing. In summary, we report hitherto undocumented effects of early Bm-L3 infection on the polarization of splenic MΦs and show how infective larvae deftly utilize the functional plasticity of host MΦs to establish themselves inside the host.

  16. A computational tool integrating host immunity with antibiotic dynamics to study tuberculosis treatment.

    Science.gov (United States)

    Pienaar, Elsje; Cilfone, Nicholas A; Lin, Philana Ling; Dartois, Véronique; Mattila, Joshua T; Butler, J Russell; Flynn, JoAnne L; Kirschner, Denise E; Linderman, Jennifer J

    2015-02-21

    While active tuberculosis (TB) is a treatable disease, many complex factors prevent its global elimination. Part of the difficulty in developing optimal therapies is the large design space of antibiotic doses, regimens and combinations. Computational models that capture the spatial and temporal dynamics of antibiotics at the site of infection can aid in reducing the design space of costly and time-consuming animal pre-clinical and human clinical trials. The site of infection in TB is the granuloma, a collection of immune cells and bacteria that form in the lung, and new data suggest that penetration of drugs throughout granulomas is problematic. Here we integrate our computational model of granuloma formation and function with models for plasma pharmacokinetics, lung tissue pharmacokinetics and pharmacodynamics for two first line anti-TB antibiotics. The integrated model is calibrated to animal data. We make four predictions. First, antibiotics are frequently below effective concentrations inside granulomas, leading to bacterial growth between doses and contributing to the long treatment periods required for TB. Second, antibiotic concentration gradients form within granulomas, with lower concentrations toward their centers. Third, during antibiotic treatment, bacterial subpopulations are similar for INH and RIF treatment: mostly intracellular with extracellular bacteria located in areas non-permissive for replication (hypoxic areas), presenting a slowly increasing target population over time. Finally, we find that on an individual granuloma basis, pre-treatment infection severity (including bacterial burden, host cell activation and host cell death) is predictive of treatment outcome. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Host ploidy, parasitism and immune defence in a coevolutionary snail-trematode system.

    Science.gov (United States)

    Osnas, E E; Lively, C M

    2006-01-01

    We studied the role of host ploidy and parasite exposure on immune defence allocation in a snail-trematode system (Potamopyrgus antipodarum-Microphallus sp.). In the field, haemocyte (the defence cell) concentration was lowest in deep-water habitats where infection is relatively low and highest in shallow-water habitats where infection is common. Because the frequency of asexual triploid snails is positively correlated with depth, we also experimentally studied the role of ploidy by exposing both diploid sexual and triploid asexual snails to Microphallus eggs. We found that triploid snails had lower haemocyte concentrations than did diploids in both parasite-addition and parasite-free treatments. We also found that both triploids and diploids increased their numbers of large granular haemocytes at similar rates after parasite exposure. Because triploid P. antipodarum have been shown to be more resistant to allopatric parasites than diploids, the current results suggest that the increased resistance of triploids is because of intrinsic genetic properties rather than to greater allocation to defence cells. This finding is consistent with recent theory on the advantages of increased ploidy for hosts combating coevolving parasites.

  18. Stimulation of host immune defenses by a small molecule protects C. elegans from bacterial infection.

    Science.gov (United States)

    Pukkila-Worley, Read; Feinbaum, Rhonda; Kirienko, Natalia V; Larkins-Ford, Jonah; Conery, Annie L; Ausubel, Frederick M

    2012-01-01

    The nematode Caenorhabditis elegans offers currently untapped potential for carrying out high-throughput, live-animal screens of low molecular weight compound libraries to identify molecules that target a variety of cellular processes. We previously used a bacterial infection assay in C. elegans to identify 119 compounds that affect host-microbe interactions among 37,214 tested. Here we show that one of these small molecules, RPW-24, protects C. elegans from bacterial infection by stimulating the host immune response of the nematode. Using transcriptome profiling, epistasis pathway analyses with C. elegans mutants, and an RNAi screen, we show that RPW-24 promotes resistance to Pseudomonas aeruginosa infection by inducing the transcription of a remarkably small number of C. elegans genes (∼1.3% of all genes) in a manner that partially depends on the evolutionarily-conserved p38 MAP kinase pathway and the transcription factor ATF-7. These data show that the immunostimulatory activity of RPW-24 is required for its efficacy and define a novel C. elegans-based strategy to identify compounds with activity against antibiotic-resistant bacterial pathogens.

  19. Stimulation of host immune defenses by a small molecule protects C. elegans from bacterial infection.

    Directory of Open Access Journals (Sweden)

    Read Pukkila-Worley

    Full Text Available The nematode Caenorhabditis elegans offers currently untapped potential for carrying out high-throughput, live-animal screens of low molecular weight compound libraries to identify molecules that target a variety of cellular processes. We previously used a bacterial infection assay in C. elegans to identify 119 compounds that affect host-microbe interactions among 37,214 tested. Here we show that one of these small molecules, RPW-24, protects C. elegans from bacterial infection by stimulating the host immune response of the nematode. Using transcriptome profiling, epistasis pathway analyses with C. elegans mutants, and an RNAi screen, we show that RPW-24 promotes resistance to Pseudomonas aeruginosa infection by inducing the transcription of a remarkably small number of C. elegans genes (∼1.3% of all genes in a manner that partially depends on the evolutionarily-conserved p38 MAP kinase pathway and the transcription factor ATF-7. These data show that the immunostimulatory activity of RPW-24 is required for its efficacy and define a novel C. elegans-based strategy to identify compounds with activity against antibiotic-resistant bacterial pathogens.

  20. A benign helminth alters the host immune system and the gut microbiota in a rat model system.

    Science.gov (United States)

    Wegener Parfrey, Laura; Jirků, Milan; Šíma, Radek; Jalovecká, Marie; Sak, Bohumil; Grigore, Karina; Jirků Pomajbíková, Kateřina

    2017-01-01

    Helminths and bacteria are major players in the mammalian gut ecosystem and each influences the host immune system and health. Declines in helminth prevalence and bacterial diversity appear to play a role in the dramatic rise of immune mediated inflammatory diseases (IMIDs) in western populations. Helminths are potent modulators of immune system and their reintroduction is a promising therapeutic avenue for IMIDs. However, the introduction of helminths represents a disturbance for the host and it is important to understand the impact of helminth reintroduction on the host, including the immune system and gut microbiome. We tested the impact of a benign tapeworm, Hymenolepis diminuta, in a rat model system. We find that H. diminuta infection results in increased interleukin 10 gene expression in the beginning of the prepatent period, consistent with induction of a type 2 immune response. We also find induction of humoral immunity during the patent period, shown here by increased IgA in feces. Further, we see an immuno-modulatory effect in the small intestine and spleen in patent period, as measured by reductions in tissue immune cells. We observed shifts in microbiota community composition during the patent period (beta-diversity) in response to H. diminuta infection. However, these compositional changes appear to be minor; they occur within families and genera common to both treatment groups. There was no change in alpha diversity. Hymenolepis diminuta is a promising model for helminth therapy because it establishes long-term, stable colonization in rats and modulates the immune system without causing bacterial dysbiosis. These results suggest that the goal of engineering a therapeutic helminth that can safely manipulate the mammalian immune system without disrupting the rest of the gut ecosystem is in reach.

  1. A benign helminth alters the host immune system and the gut microbiota in a rat model system.

    Directory of Open Access Journals (Sweden)

    Laura Wegener Parfrey

    Full Text Available Helminths and bacteria are major players in the mammalian gut ecosystem and each influences the host immune system and health. Declines in helminth prevalence and bacterial diversity appear to play a role in the dramatic rise of immune mediated inflammatory diseases (IMIDs in western populations. Helminths are potent modulators of immune system and their reintroduction is a promising therapeutic avenue for IMIDs. However, the introduction of helminths represents a disturbance for the host and it is important to understand the impact of helminth reintroduction on the host, including the immune system and gut microbiome. We tested the impact of a benign tapeworm, Hymenolepis diminuta, in a rat model system. We find that H. diminuta infection results in increased interleukin 10 gene expression in the beginning of the prepatent period, consistent with induction of a type 2 immune response. We also find induction of humoral immunity during the patent period, shown here by increased IgA in feces. Further, we see an immuno-modulatory effect in the small intestine and spleen in patent period, as measured by reductions in tissue immune cells. We observed shifts in microbiota community composition during the patent period (beta-diversity in response to H. diminuta infection. However, these compositional changes appear to be minor; they occur within families and genera common to both treatment groups. There was no change in alpha diversity. Hymenolepis diminuta is a promising model for helminth therapy because it establishes long-term, stable colonization in rats and modulates the immune system without causing bacterial dysbiosis. These results suggest that the goal of engineering a therapeutic helminth that can safely manipulate the mammalian immune system without disrupting the rest of the gut ecosystem is in reach.

  2. IPNV with high and low virulence: host immune responses and viral mutations during infection

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    Skjesol Astrid

    2011-08-01

    Full Text Available Abstract Background Infectious pancreatic necrosis virus (IPNV is an aquatic member of the Birnaviridae family that causes widespread disease in salmonids. IPNV is represented by multiple strains with markedly different virulence. Comparison of isolates reveals hyper variable regions (HVR, which are presumably associated with pathogenicity. However little is known about the rates and modes of sequence divergence and molecular mechanisms that determine virulence. Also how the host response may influence IPNV virulence is poorly described. Methods In this study we compared two field isolates of IPNV (NFH-Ar and NFH-El. The sequence changes, replication and mortality were assessed following experimental challenge of Atlantic salmon. Gene expression analyses with qPCR and microarray were applied to examine the immune responses in head kidney. Results Significant differences in mortality were observed between the two isolates, and viral load in the pancreas at 13 days post infection (d p.i. was more than 4 orders of magnitude greater for NFH-Ar in comparison with NFH-El. Sequence comparison of five viral genes from the IPNV isolates revealed different mutation rates and Ka/Ks ratios. A strong tendency towards non-synonymous mutations was found in the HRV of VP2 and in VP3. All mutations in VP5 produced precocious stop codons. Prior to the challenge, NFH-Ar and NFH-El possessed high and low virulence motifs in VP2, respectively. Nucleotide substitutions were noticed already during passage of viruses in CHSE-214 cells and their accumulation continued in the challenged fish. The sequence changes were notably directed towards low virulence. Co-ordinated activation of anti-viral genes with diverse functions (IFN-a1 and c, sensors - Rig-I, MDA-5, TLR8 and 9, signal transducers - Srk2, MyD88, effectors - Mx, galectin 9, galectin binding protein, antigen presentation - b2-microglobulin was observed at 13 d p.i. (NFH-Ar and 29 d p.i. (both isolates

  3. Multiple candidate effectors from the oomycete pathogen Hyaloperonospora arabidopsidis suppress host plant immunity.

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    Georgina Fabro

    2011-11-01

    Full Text Available Oomycete pathogens cause diverse plant diseases. To successfully colonize their hosts, they deliver a suite of effector proteins that can attenuate plant defenses. In the oomycete downy mildews, effectors carry a signal peptide and an RxLR motif. Hyaloperonospora arabidopsidis (Hpa causes downy mildew on the model plant Arabidopsis thaliana (Arabidopsis. We investigated if candidate effectors predicted in the genome sequence of Hpa isolate Emoy2 (HaRxLs were able to manipulate host defenses in different Arabidopsis accessions. We developed a rapid and sensitive screening method to test HaRxLs by delivering them via the bacterial type-three secretion system (TTSS of Pseudomonas syringae pv tomato DC3000-LUX (Pst-LUX and assessing changes in Pst-LUX growth in planta on 12 Arabidopsis accessions. The majority (~70% of the 64 candidates tested positively contributed to Pst-LUX growth on more than one accession indicating that Hpa virulence likely involves multiple effectors with weak accession-specific effects. Further screening with a Pst mutant (ΔCEL showed that HaRxLs that allow enhanced Pst-LUX growth usually suppress callose deposition, a hallmark of pathogen-associated molecular pattern (PAMP-triggered immunity (PTI. We found that HaRxLs are rarely strong avirulence determinants. Although some decreased Pst-LUX growth in particular accessions, none activated macroscopic cell death. Fewer HaRxLs conferred enhanced Pst growth on turnip, a non-host for Hpa, while several reduced it, consistent with the idea that turnip's non-host resistance against Hpa could involve a combination of recognized HaRxLs and ineffective HaRxLs. We verified our results by constitutively expressing in Arabidopsis a sub-set of HaRxLs. Several transgenic lines showed increased susceptibility to Hpa and attenuation of Arabidopsis PTI responses, confirming the HaRxLs' role in Hpa virulence. This study shows TTSS screening system provides a useful tool to test whether

  4. Cell-mediated immunity to histocompatibility antigens : controlling factors, with emphasis on Graft-versus-host reactions in mice

    NARCIS (Netherlands)

    H. Bril (Herman)

    1984-01-01

    textabstractGraft-versus-Host (GvH) disease is characterized by weight loss, diarrhea, skin lesions, hypofunction of the immune system with concomitant infections, etc. This syndrome is potentially lethal. GvH reactions, which underly this disease, may occur when immunocompetent T lymphocytes are

  5. Spitting Image: Tick Saliva Assists the Causative Agent of Lyme Disease in Evading Host Skin's Innate Immune Response

    NARCIS (Netherlands)

    Hovius, Joppe W. R.

    2009-01-01

    Lyme disease is caused by the spirochete Borrelia burgdorferi and is transmitted through ticks. Inhibition of host skin's innate immune response might be instrumental to both tick feeding and B. burgdorferi transmission. The article by Marchal et al. describes how tick saliva suppresses B.

  6. The cellular immune response of Daphnia magna under host-parasite genetic variation and variation in initial dose.

    Science.gov (United States)

    Auld, Stuart K J R; Edel, Kai H; Little, Tom J

    2012-10-01

    In invertebrate-parasite systems, the likelihood of infection following parasite exposure is often dependent on the specific combination of host and parasite genotypes (termed genetic specificity). Genetic specificity can maintain diversity in host and parasite populations and is a major component of the Red Queen hypothesis. However, invertebrate immune systems are thought to only distinguish between broad classes of parasite. Using a natural host-parasite system with a well-established pattern of genetic specificity, the crustacean Daphnia magna and its bacterial parasite Pasteuria ramosa, we found that only hosts from susceptible host-parasite genetic combinations mounted a cellular response following exposure to the parasite. These data are compatible with the hypothesis that genetic specificity is attributable to barrier defenses at the site of infection (the gut), and that the systemic immune response is general, reporting the number of parasite spores entering the hemocoel. Further supporting this, we found that larger cellular responses occurred at higher initial parasite doses. By studying the natural infection route, where parasites must pass barrier defenses before interacting with systemic immune responses, these data shed light on which components of invertebrate defense underlie genetic specificity. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

  7. Studies on the cellular immune response in patients with upper urinary tract carcinoma compawed with those in patients with bladder carcinoma and it's postoperative change

    International Nuclear Information System (INIS)

    Sakai, Shunsuke

    1980-01-01

    Non-specific cellular immunity of patients with upper urinary tract carcinoma was studied by PPD reaction (in vivo or in vitro), lymphocytes subpopulation and macrophage migration inhibition test and the results were compared with those of patients with bladder carcinoma or benign urological diseases. 1) The preoperative cellular immunity of the malignant tumor group gave low values as compared to that in the benign disease group. Although the cellular immunity of patients with renal cell carcinoma showed no difference in the points of their grade and stage, significant differences were noted in patients with bladder carcinoma. The patients with renal pelvic and ureter carcinoma appeared to be similar to the patients with bladder carcinoma in the aspects of immune reactions. 2) In the majority of patients with upper urinary tract and bladder carcinoma, the cellular immunity after complete removal of the carcinoma gave an increased value of each marker as compared to the preoperative value. 3) The cellular immunity after irradiation decreased in the majority of the cases in terms of PPD reaction and T-cell ratio in lymphocyte subpopulation. Irradiation of 4000 - 6000 Rad. showed greater influence on T-cell than on B-cell, but influence of irradiation on cellular immunity was not different by irradiation dose. 4) The cellular immunity indicated decreased values for one to two months after discontinuation of irradiation, but then it showed a tendency to increase in terms of PPD and lymphocytes subpopulation in the patients with satisfactory postoperative courses. 5) Through the pre and postoperative courses, the immunity of the carcinomatous stage seems to be reflected better by the T-cell ratio than by the absolute number of T-cell. It is likely that macrophage migration inhibition test shows much sharper reaction than PPD reaction. (author)

  8. Host lung immunity is severely compromised during tropical pulmonary eosinophilia: role of lung eosinophils and macrophages.

    Science.gov (United States)

    Sharma, Pankaj; Sharma, Aditi; Vishwakarma, Achchhe Lal; Agnihotri, Promod Kumar; Sharma, Sharad; Srivastava, Mrigank

    2016-04-01

    Eosinophils play a central role in the pathogenesis of tropical pulmonary eosinophilia, a rare, but fatal, manifestation of filariasis. However, no exhaustive study has been done to identify the genes and proteins of eosinophils involved in the pathogenesis of tropical pulmonary eosinophilia. In the present study, we established a mouse model of tropical pulmonary eosinophilia that mimicked filarial manifestations of human tropical pulmonary eosinophilia pathogenesis and used flow cytometry-assisted cell sorting and real-time RT-PCR to study the gene expression profile of flow-sorted, lung eosinophils and lung macrophages during tropical pulmonary eosinophilia pathogenesis. Our results show that tropical pulmonary eosinophilia mice exhibited increased levels of IL-4, IL-5, CCL5, and CCL11 in the bronchoalveolar lavage fluid and lung parenchyma along with elevated titers of IgE and IgG subtypes in the serum. Alveolar macrophages from tropical pulmonary eosinophilia mice displayed decreased phagocytosis, attenuated nitric oxide production, and reduced T-cell proliferation capacity, and FACS-sorted lung eosinophils from tropical pulmonary eosinophilia mice upregulated transcript levels of ficolin A and anti-apoptotic gene Bcl2,but proapoptotic genes Bim and Bax were downregulated. Similarly, flow-sorted lung macrophages upregulated transcript levels of TLR-2, TLR-6, arginase-1, Ym-1, and FIZZ-1 but downregulated nitric oxide synthase-2 levels, signifying their alternative activation. Taken together, we show that the pathogenesis of tropical pulmonary eosinophilia is marked by functional impairment of alveolar macrophages, alternative activation of lung macrophages, and upregulation of anti-apoptotic genes by eosinophils. These events combine together to cause severe lung inflammation and compromised lung immunity. Therapeutic interventions that can boost host immune response in the lungs might thus provide relief to patients with tropical pulmonary eosinophilia.

  9. Effector-Triggered Immunity Determines Host Genotype-Specific Incompatibility in Legume-Rhizobium Symbiosis.

    Science.gov (United States)

    Yasuda, Michiko; Miwa, Hiroki; Masuda, Sachiko; Takebayashi, Yumiko; Sakakibara, Hitoshi; Okazaki, Shin

    2016-08-01

    Symbiosis between legumes and rhizobia leads to the formation of N2-fixing root nodules. In soybean, several host genes, referred to as Rj genes, control nodulation. Soybean cultivars carrying the Rj4 gene restrict nodulation by specific rhizobia such as Bradyrhizobium elkanii We previously reported that the restriction of nodulation was caused by B. elkanii possessing a functional type III secretion system (T3SS), which is known for its delivery of virulence factors by pathogenic bacteria. In the present study, we investigated the molecular basis for the T3SS-dependent nodulation restriction in Rj4 soybean. Inoculation tests revealed that soybean cultivar BARC-2 (Rj4/Rj4) restricted nodulation by B. elkanii USDA61, whereas its nearly isogenic line BARC-3 (rj4/rj4) formed nitrogen-fixing nodules with the same strain. Root-hair curling and infection threads were not observed in the roots of BARC-2 inoculated with USDA61, indicating that Rj4 blocked B. elkanii infection in the early stages. Accumulation of H2O2 and salicylic acid (SA) was observed in the roots of BARC-2 inoculated with USDA61. Transcriptome analyses revealed that inoculation of USDA61, but not its T3SS mutant in BARC-2, induced defense-related genes, including those coding for hypersensitive-induced responsive protein, which act in effector-triggered immunity (ETI) in Arabidopsis. These findings suggest that B. elkanii T3SS triggers the SA-mediated ETI-type response in Rj4 soybean, which consequently blocks symbiotic interactions. This study revealed a common molecular mechanism underlying both plant-pathogen and plant-symbiont interactions, and suggests that establishment of a root nodule symbiosis requires the evasion or suppression of plant immune responses triggered by rhizobial effectors. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  10. Brain microbial populations in HIV/AIDS: α-proteobacteria predominate independent of host immune status.

    Directory of Open Access Journals (Sweden)

    William G Branton

    Full Text Available The brain is assumed to be a sterile organ in the absence of disease although the impact of immune disruption is uncertain in terms of brain microbial diversity or quantity. To investigate microbial diversity and quantity in the brain, the profile of infectious agents was examined in pathologically normal and abnormal brains from persons with HIV/AIDS [HIV] (n = 12, other disease controls [ODC] (n = 14 and in cerebral surgical resections for epilepsy [SURG] (n = 6. Deep sequencing of cerebral white matter-derived RNA from the HIV (n = 4 and ODC (n = 4 patients and SURG (n = 2 groups revealed bacterially-encoded 16 s RNA sequences in all brain specimens with α-proteobacteria representing over 70% of bacterial sequences while the other 30% of bacterial classes varied widely. Bacterial rRNA was detected in white matter glial cells by in situ hybridization and peptidoglycan immunoreactivity was also localized principally in glia in human brains. Analyses of amplified bacterial 16 s rRNA sequences disclosed that Proteobacteria was the principal bacterial phylum in all human brain samples with similar bacterial rRNA quantities in HIV and ODC groups despite increased host neuroimmune responses in the HIV group. Exogenous viruses including bacteriophage and human herpes viruses-4, -5 and -6 were detected variably in autopsied brains from both clinical groups. Brains from SIV- and SHIV-infected macaques displayed a profile of bacterial phyla also dominated by Proteobacteria but bacterial sequences were not detected in experimentally FIV-infected cat or RAG1⁻/⁻ mouse brains. Intracerebral implantation of human brain homogenates into RAG1⁻/⁻ mice revealed a preponderance of α-proteobacteria 16 s RNA sequences in the brains of recipient mice at 7 weeks post-implantation, which was abrogated by prior heat-treatment of the brain homogenate. Thus, α-proteobacteria represented the major bacterial component of the primate brain

  11. Trypanosome infection establishment in the tsetse fly gut is influenced by microbiome-regulated host immune barriers.

    Directory of Open Access Journals (Sweden)

    Brian L Weiss

    Full Text Available Tsetse flies (Glossina spp. vector pathogenic African trypanosomes, which cause sleeping sickness in humans and nagana in domesticated animals. Additionally, tsetse harbors 3 maternally transmitted endosymbiotic bacteria that modulate their host's physiology. Tsetse is highly resistant to infection with trypanosomes, and this phenotype depends on multiple physiological factors at the time of challenge. These factors include host age, density of maternally-derived trypanolytic effector molecules present in the gut, and symbiont status during development. In this study, we investigated the molecular mechanisms that result in tsetse's resistance to trypanosomes. We found that following parasite challenge, young susceptible tsetse present a highly attenuated immune response. In contrast, mature refractory flies express higher levels of genes associated with humoral (attacin and pgrp-lb and epithelial (inducible nitric oxide synthase and dual oxidase immunity. Additionally, we discovered that tsetse must harbor its endogenous microbiome during intrauterine larval development in order to present a parasite refractory phenotype during adulthood. Interestingly, mature aposymbiotic flies (Gmm(Apo present a strong immune response earlier in the infection process than do WT flies that harbor symbiotic bacteria throughout their entire lifecycle. However, this early response fails to confer significant resistance to trypanosomes. Gmm(Apo adults present a structurally compromised peritrophic matrix (PM, which lines the fly midgut and serves as a physical barrier that separates luminal contents from immune responsive epithelial cells. We propose that the early immune response we observe in Gmm(Apo flies following parasite challenge results from the premature exposure of gut epithelia to parasite-derived immunogens in the absence of a robust PM. Thus, tsetse's PM appears to regulate the timing of host immune induction following parasite challenge. Our results

  12. Host immunity in the protective response to vaccination with heat-killed Burkholderia mallei

    Directory of Open Access Journals (Sweden)

    Paessler Slobodan

    2008-09-01

    Full Text Available Abstract Background We performed initial cell, cytokine and complement depletion studies to investigate the possible role of these effectors in response to vaccination with heat-killed Burkholderia mallei in a susceptible BALB/c mouse model of infection. Results While protection with heat-killed bacilli did not result in sterilizing immunity, limited protection was afforded against an otherwise lethal infection and provided insight into potential host protective mechanisms. Our results demonstrated that mice depleted of either B cells, TNF-α or IFN-γ exhibited decreased survival rates, indicating a role for these effectors in obtaining partial protection from a lethal challenge by the intraperitoneal route. Additionally, complement depletion had no effect on immunoglobulin production when compared to non-complement depleted controls infected intranasally. Conclusion The data provide a basis for future studies of protection via vaccination using either subunit or whole-organism vaccine preparations from lethal infection in the experimental BALB/c mouse model. The results of this study demonstrate participation of B220+ cells and pro-inflammatory cytokines IFN-γ and TNF-α in protection following HK vaccination.

  13. A pox on thee! Manipulation of the host immune system by myxoma virus and implications for viral-host co-adaptation.

    Science.gov (United States)

    Zúñiga, Martha C

    2002-09-01

    The poxviruses have evolved a diverse array of proteins which serve to subvert innate and adaptive host responses that abort or at least limit viral infections. Myxoma virus and its rabbit host are considered to represent an ideal poxvirus-host system in which to study the effects of these immunomodulatory proteins. Studies of laboratory rabbits (Oryctolagus cuniculus) infected with gene knockout variants of myxoma virus have provided compelling evidence that several myxoma virus gene products contribute to the pathogenic condition known as myxomatosis. However, myxomatosis, which is characterized by skin lesions, systemic immunosuppression, and a high mortality rate, does not occur in the virus' natural South American host, Sylvilogus brasiliensis. Moreover, in Australia where myxoma virus was willfully introduced to control populations of O. cuniculus, myxomatosis-resistant rabbits emerged within a year of myxoma virus introduction into the field. In this review I discuss the characterized immunomodulatory proteins of myxoma virus, their biochemical properties, their pathogenic effects in laboratory rabbits, the role of the host immune system in the susceptibility or resistance to myxomatosis, and the evidence that immunomodulatory genes may have been attenuated during the co-adaptation of myxoma virus and O. cuniculus in Australia.

  14. Mechanisms of Host-Pathogen Protein Complex Formation and Bacterial Immune Evasion of Streptococcus suis Protein Fhb.

    Science.gov (United States)

    Li, Xueqin; Liu, Peng; Gan, Shuzhen; Zhang, Chunmao; Zheng, Yuling; Jiang, Yongqiang; Yuan, Yuan

    2016-08-12

    Streptococcus suis serotype 2 (S. suis 2)-induced sepsis and meningitis are often accompanied by bacteremia. The evasion of polymorphonuclear leukocyte-mediated phagocytic clearance is central to the establishment of bacteremia caused by S. suis 2 and is facilitated by the ability of factor H (FH)-binding protein (Fhb) to bind FH on the bacterial surface, thereby impeding alternative pathway complement activation and phagocytic clearance. Here, C3b/C3d was found to bind to Fhb, along with FH, forming a large immune complex. The formation of this immune complex was mediated by domain II of Fhb via electrostatic and hydrophobic interactions, which, to our knowledge, is a new type of interaction. Interestingly, Fhb was found to be associated with the cell envelope and also present in the culture supernatant, where secreted Fhb inhibited complement activation via interactions with domain II, thereby enhancing antiphagocytic clearance by polymorphonuclear leukocytes. Thus, Fhb is a multifunctional bacterial protein, which binds host complement component C3 as well as FH and interferes with innate immune recognition in a secret protein manner. S. suis 2 therefore appears to have developed a new strategy to combat host innate immunity and enhance survival in host blood. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Mechanisms of Host-Pathogen Protein Complex Formation and Bacterial Immune Evasion of Streptococcus suis Protein Fhb*

    Science.gov (United States)

    Li, Xueqin; Liu, Peng; Gan, Shuzhen; Zhang, Chunmao; Zheng, Yuling; Jiang, Yongqiang; Yuan, Yuan

    2016-01-01

    Streptococcus suis serotype 2 (S. suis 2)-induced sepsis and meningitis are often accompanied by bacteremia. The evasion of polymorphonuclear leukocyte-mediated phagocytic clearance is central to the establishment of bacteremia caused by S. suis 2 and is facilitated by the ability of factor H (FH)-binding protein (Fhb) to bind FH on the bacterial surface, thereby impeding alternative pathway complement activation and phagocytic clearance. Here, C3b/C3d was found to bind to Fhb, along with FH, forming a large immune complex. The formation of this immune complex was mediated by domain II of Fhb via electrostatic and hydrophobic interactions, which, to our knowledge, is a new type of interaction. Interestingly, Fhb was found to be associated with the cell envelope and also present in the culture supernatant, where secreted Fhb inhibited complement activation via interactions with domain II, thereby enhancing antiphagocytic clearance by polymorphonuclear leukocytes. Thus, Fhb is a multifunctional bacterial protein, which binds host complement component C3 as well as FH and interferes with innate immune recognition in a secret protein manner. S. suis 2 therefore appears to have developed a new strategy to combat host innate immunity and enhance survival in host blood. PMID:27342778

  16. Association of the Host Immune Response with Protection Using a Live Attenuated African Swine Fever Virus Model.

    Science.gov (United States)

    Carlson, Jolene; O'Donnell, Vivian; Alfano, Marialexia; Velazquez Salinas, Lauro; Holinka, Lauren G; Krug, Peter W; Gladue, Douglas P; Higgs, Stephen; Borca, Manuel V

    2016-10-22

    African swine fever (ASF) is a lethal hemorrhagic disease of swine caused by a double-stranded DNA virus, ASF virus (ASFV). There is no vaccine to prevent the disease and current control measures are limited to culling and restricting animal movement. Swine infected with attenuated strains are protected against challenge with a homologous virulent virus, but there is limited knowledge of the host immune mechanisms generating that protection. Swine infected with Pretoriuskop/96/4 (Pret4) virus develop a fatal severe disease, while a derivative strain lacking virulence-associated gene 9GL (Pret4Δ9GL virus) is completely attenuated. Swine infected with Pret4Δ9GL virus and challenged with the virulent parental virus at 7, 10, 14, 21, and 28 days post infection (dpi) showed a progressive acquisition of protection (from 40% at 7 dpi to 80% at 21 and 28 dpi). This animal model was used to associate the presence of host immune response (ASFV-specific antibody and interferon (IFN)-γ responses, or specific cytokine profiles) and protection against challenge. With the exception of ASFV-specific antibodies in survivors challenged at 21 and 28 dpi, no association between the parameters assessed and protection could be established. These results, encompassing data from 65 immunized swine, underscore the complexity of the system under study, suggesting that protection relies on the concurrence of different host immune mechanisms.

  17. Association of the Host Immune Response with Protection Using a Live Attenuated African Swine Fever Virus Model

    Directory of Open Access Journals (Sweden)

    Jolene Carlson

    2016-10-01

    Full Text Available African swine fever (ASF is a lethal hemorrhagic disease of swine caused by a double-stranded DNA virus, ASF virus (ASFV. There is no vaccine to prevent the disease and current control measures are limited to culling and restricting animal movement. Swine infected with attenuated strains are protected against challenge with a homologous virulent virus, but there is limited knowledge of the host immune mechanisms generating that protection. Swine infected with Pretoriuskop/96/4 (Pret4 virus develop a fatal severe disease, while a derivative strain lacking virulence-associated gene 9GL (Pret4Δ9GL virus is completely attenuated. Swine infected with Pret4Δ9GL virus and challenged with the virulent parental virus at 7, 10, 14, 21, and 28 days post infection (dpi showed a progressive acquisition of protection (from 40% at 7 dpi to 80% at 21 and 28 dpi. This animal model was used to associate the presence of host immune response (ASFV-specific antibody and interferon (IFN-γ responses, or specific cytokine profiles and protection against challenge. With the exception of ASFV-specific antibodies in survivors challenged at 21 and 28 dpi, no association between the parameters assessed and protection could be established. These results, encompassing data from 65 immunized swine, underscore the complexity of the system under study, suggesting that protection relies on the concurrence of different host immune mechanisms.

  18. How Human Papillomavirus Replication and Immune Evasion Strategies Take Advantage of the Host DNA Damage Repair Machinery.

    Science.gov (United States)

    Bordignon, Valentina; Di Domenico, Enea Gino; Trento, Elisabetta; D'Agosto, Giovanna; Cavallo, Ilaria; Pontone, Martina; Pimpinelli, Fulvia; Mariani, Luciano; Ensoli, Fabrizio

    2017-12-19

    The DNA damage response (DDR) is a complex signalling network activated when DNA is altered by intrinsic or extrinsic agents. DDR plays important roles in genome stability and cell cycle regulation, as well as in tumour transformation. Viruses have evolved successful life cycle strategies in order to ensure a chronic persistence in the host, virtually avoiding systemic sequelae and death. This process promotes the periodic shedding of large amounts of infectious particles to maintain a virus reservoir in individual hosts, while allowing virus spreading within the community. To achieve such a successful lifestyle, the human papilloma virus (HPV) needs to escape the host defence systems. The key to understanding how this is achieved is in the virus replication process that provides by itself an evasion mechanism by inhibiting and delaying the host immune response against the viral infection. Numerous studies have demonstrated that HPV exploits both the ataxia-telangiectasia mutated (ATM) and ataxia-telangiectasia and rad3-related (ATR) DDR pathways to replicate its genome and maintain a persistent infection by downregulating the innate and cell-mediated immunity. This review outlines how HPV interacts with the ATM- and ATR-dependent DDR machinery during the viral life cycle to create an environment favourable to viral replication, and how the interaction with the signal transducers and activators of transcription (STAT) protein family and the deregulation of the Janus kinase (JAK)-STAT pathways may impact the expression of interferon-inducible genes and the innate immune responses.

  19. Silencing the Honey Bee (Apis mellifera) Naked Cuticle Gene (nkd) Improves Host Immune Function and Reduces Nosema ceranae Infections

    Science.gov (United States)

    Li, Wenfeng; Evans, Jay D.; Huang, Qiang; Rodríguez-García, Cristina; Liu, Jie; Hamilton, Michele; Grozinger, Christina M.; Webster, Thomas C.; Su, Songkun

    2016-01-01

    ABSTRACT Nosema ceranae is a new and emerging microsporidian parasite of European honey bees, Apis mellifera, that has been implicated in colony losses worldwide. RNA interference (RNAi), a posttranscriptional gene silencing mechanism, has emerged as a potent and specific strategy for controlling infections of parasites and pathogens in honey bees. While previous studies have focused on the silencing of parasite/pathogen virulence factors, we explore here the possibility of silencing a host factor as a mechanism for reducing parasite load. Specifically, we used an RNAi strategy to reduce the expression of a honey bee gene, naked cuticle (nkd), which is a negative regulator of host immune function. Our studies found that nkd mRNA levels in adult bees were upregulated by N. ceranae infection (and thus, the parasite may use this mechanism to suppress host immune function) and that ingestion of double-stranded RNA (dsRNA) specific to nkd efficiently silenced its expression. Furthermore, we found that RNAi-mediated knockdown of nkd transcripts in Nosema-infected bees resulted in upregulation of the expression of several immune genes (Abaecin, Apidaecin, Defensin-1, and PGRP-S2), reduction of Nosema spore loads, and extension of honey bee life span. The results of our studies clearly indicate that silencing the host nkd gene can activate honey bee immune responses, suppress the reproduction of N. ceranae, and improve the overall health of honey bees. This study represents a novel host-derived therapeutic for honey bee disease treatment that merits further exploration. IMPORTANCE Given the critical role of honey bees in the pollination of agricultural crops, it is urgent to develop strategies to prevent the colony decline induced by the infection of parasites/pathogens. Targeting parasites and pathogens directly by RNAi has been proven to be useful for controlling infections in honey bees, but little is known about the disease impacts of RNAi silencing of host factors

  20. Role of Neurochemicals in the Interaction between the Microbiota and the Immune and the Nervous System of the Host Organism.

    Science.gov (United States)

    Oleskin, Alexander V; Shenderov, Boris A; Rogovsky, Vladimir S

    2017-09-01

    This work is concerned with the role of evolutionary conserved substances, neurotransmitters, and neurohormones, within the complex framework of the microbial consortium-immune system-nervous system axis in the human or animal organism. Although the operation of each of these systems per se is relatively well understood, their combined effects on the host organism still await further research. Drawing on recent research on host-produced and microbial low-molecular-weight neurochemicals such as biogenic amines, amino acids, and short-chain fatty acids (SCFAs), we suggest that these mediators form a part of a universal neurochemical "language." It mediates the whole gamut of harmonious and disharmonious interactions between (a) the intestinal microbial consortium, (b) local and systemic immune cells, and (c) the central and peripheral nervous system. Importantly, the ongoing microbiota-host interactivity is bidirectional. We present evidence that a large number of microbially produced low-molecular-weight compounds are identical or homologous to mediators that are synthesized by immune or nervous cells and, therefore, can bind to the corresponding host receptors. In addition, microbial cells specifically respond to host-produced neuromediators/neurohormones because they have adapted to them during the course of many millions of years of microbiota-host coevolution. We emphasize that the terms "microbiota" and "microbial consortium" are to be used in the broadest sense, so as to include, apart from bacteria, also eukaryotic microorganisms. These are exemplified by the mycobiota whose role in the microbial consortium-immune system-nervous system axis researchers are only beginning to elucidate. In light of the above, it is imperative to reform the current strategies of using probiotic microorganisms and their metabolites for treating and preventing dysbiosis-related diseases. The review demonstrates, in the example of novel probiotics (psychobiotics), that many target

  1. Silencing the Honey Bee (Apis mellifera) Naked Cuticle Gene (nkd) Improves Host Immune Function and Reduces Nosema ceranae Infections.

    Science.gov (United States)

    Li, Wenfeng; Evans, Jay D; Huang, Qiang; Rodríguez-García, Cristina; Liu, Jie; Hamilton, Michele; Grozinger, Christina M; Webster, Thomas C; Su, Songkun; Chen, Yan Ping

    2016-11-15

    Nosema ceranae is a new and emerging microsporidian parasite of European honey bees, Apis mellifera, that has been implicated in colony losses worldwide. RNA interference (RNAi), a posttranscriptional gene silencing mechanism, has emerged as a potent and specific strategy for controlling infections of parasites and pathogens in honey bees. While previous studies have focused on the silencing of parasite/pathogen virulence factors, we explore here the possibility of silencing a host factor as a mechanism for reducing parasite load. Specifically, we used an RNAi strategy to reduce the expression of a honey bee gene, naked cuticle (nkd), which is a negative regulator of host immune function. Our studies found that nkd mRNA levels in adult bees were upregulated by N. ceranae infection (and thus, the parasite may use this mechanism to suppress host immune function) and that ingestion of double-stranded RNA (dsRNA) specific to nkd efficiently silenced its expression. Furthermore, we found that RNAi-mediated knockdown of nkd transcripts in Nosema-infected bees resulted in upregulation of the expression of several immune genes (Abaecin, Apidaecin, Defensin-1, and PGRP-S2), reduction of Nosema spore loads, and extension of honey bee life span. The results of our studies clearly indicate that silencing the host nkd gene can activate honey bee immune responses, suppress the reproduction of N. ceranae, and improve the overall health of honey bees. This study represents a novel host-derived therapeutic for honey bee disease treatment that merits further exploration. Given the critical role of honey bees in the pollination of agricultural crops, it is urgent to develop strategies to prevent the colony decline induced by the infection of parasites/pathogens. Targeting parasites and pathogens directly by RNAi has been proven to be useful for controlling infections in honey bees, but little is known about the disease impacts of RNAi silencing of host factors. Here, we demonstrate

  2. A clinical study of postoperative changes in immunity of patients with digestive organ cancers and effectiveness of oriental medicine in esophageal cancer preoperative irradiation therapy

    International Nuclear Information System (INIS)

    Yamada, Teruji

    1993-01-01

    In esophageal cancer, the operative stress caused by thoracotomy and laparotomy is great and, postoperatively, immunity suppressive conditions are seen. Again, it is a known fact that when irradiation is applied pre- and postoperatively, the immunity aptitude will drop even further. Experimentally, Juzen-taiho-to is an oriental medicine reported as having immunity suppressive preventive effects. Juzen-taiho-to is also reported as effective in decreasing side effects caused by anti-cancer agents. However, detailed reports on administration effects of Juzen-taiho-to against irradiation therapy for esophageal cancer has yet to be seen. This time, studies were made on the administration effects of Juzen-taiho-to in esophageal cancer. The subjects of examination were 21 cases in which preoperative irradiation therapy and curative resection was made. Also, 46 cases of non-irradiation therapy and curative resection were studied. These cases were divided into two groups: the Juzen-taiho-to dosaged group (JT), and the non-dosaged (controlled) group (NJT). The hemoglobin value in the irradiated and non-irradiated group did not display apparent differences in both the JT group and the NJT group. In blood serum albumin value, at one month postoperatively, an improvement trend was seen in the JT group as opposed to the NJT group. (author)

  3. DMPD: Toll-like receptors and the host defense against microbial pathogens: bringingspecificity to the innate-immune system. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15075354 Toll-like receptors and the host defense against microbial pathogens: brin...oc Biol. 2004 May;75(5):749-55. Epub 2004 Jan 14. (.png) (.svg) (.html) (.csml) Show Toll-like receptors and the host defense again...immune system. PubmedID 15075354 Title Toll-like receptors and the host defense against microbial pathogens:

  4. Host-Brucella interactions and the Brucella genome as tools for subunit antigen discovery and immunization against brucellosis

    Science.gov (United States)

    Gomez, Gabriel; Adams, Leslie G.; Rice-Ficht, Allison; Ficht, Thomas A.

    2013-01-01

    Vaccination is the most important approach to counteract infectious diseases. Thus, the development of new and improved vaccines for existing, emerging, and re-emerging diseases is an area of great interest to the scientific community and general public. Traditional approaches to subunit antigen discovery and vaccine development lack consideration for the critical aspects of public safety and activation of relevant protective host immunity. The availability of genomic sequences for pathogenic Brucella spp. and their hosts have led to development of systems-wide analytical tools that have provided a better understanding of host and pathogen physiology while also beginning to unravel the intricacies at the host-pathogen interface. Advances in pathogen biology, host immunology, and host-agent interactions have the potential to serve as a platform for the design and implementation of better-targeted antigen discovery approaches. With emphasis on Brucella spp., we probe the biological aspects of host and pathogen that merit consideration in the targeted design of subunit antigen discovery and vaccine development. PMID:23720712

  5. Immune competence of splenic lymphocytes following graft-vs-host disease in mouse allogeneic radiation chimeras

    International Nuclear Information System (INIS)

    Urso, P.; Gengozian, N.

    1977-01-01

    The abnormal immune response of long-term mouse allogeneic chimeras is reflected by qualitative deficiencies in either T or B lymphocytes. The present study was undertaken to determine if a relationship existed between the severity of graft-vs-host disease (GVHD) that these animals had experienced and a functional defect in either the T or B cell population. The in vitro PFC response of chimera spleen cells to sheep red blood cells (SRBC) was evaluated in the presence of normal T or B lymphocytes 4 to 8 months after marrow transplantation and well beyond the GVHD period. In an analysis of several different allogeneic radiation chimeras, our results showed no relationship between the severity of GVHD experienced and the immunologic capacity of either T or B cells. Thus, different chimera combinations showing similar degrees of GVHD were functionally deficient in one or the other of these two cells types or both with no apparent predilection for abnormality in either population. In examining the quantitative in vitro PFC response to sheep RBC by spleen cells from individual chimeras, we found that the number of PFC formed was related to the severity of GVHD experienced by that animal. A general relationship between severity of GVHD and PFC capacity may also exist between chimeras of different genetic combinations. However, this relationship is not precise since gross exceptions occur. Our results, although documenting further the qualitative abnormalities in T and/or B lymphocytes of radiation chimeras, do not reveal the factor or mechanisms by which these cells are made unresponsive. It is suggested that the tolerance-inducing mechanism of these animals, whether it be humoral blocking factors or suppressor cells, is in some way interfering with the collaboration of T and B cells for antibody production

  6. Disease susceptibiliy in the zig-zag model of host-microbe Interactions: only a consequence of immune suppression?

    OpenAIRE

    Keller, Harald; Boyer, Laurent; Abad, Pierre

    2016-01-01

    For almost ten years, the Zig-Zag model has provided a convenient framework for explaining the molecular bases of compatibility and incompatibility in plant-microbe interactions (Jones and Dangl, 2006). According to the Zig-Zag model, disease susceptibility is a consequence of the suppression of host immunity during the evolutionary arms race between plants and pathogens. The Zig-Zag model thus fits well with biotrophic interactions, but is less applicable to interactions involving pathogens ...

  7. Comparison of innate and Th1-type host immune responses inOesophagostomum dentatumandTrichuris suisinfections in pigs

    DEFF Research Database (Denmark)

    Andreasen, Annette; Skovgaard, Kerstin; Klaver, Elsenoor J.

    2016-01-01

    with two groups trickle inoculated with 10 T. suis eggs/kg/day (Group T) or 20 O. dentatum L3/kg/day (O). Another group (OT) was infected with both parasites. Group C remained uninfected. Expression of innate and Th1/Treg cell associated genes in gut mucosa and associated lymph nodes was determined by q....... Surprisingly, O. dentatum E/S products induced a significant (p helminth-host immune response interaction....

  8. Influence of postoperative enteral nutrition on cellular immunity. A random double-blinded placebo controlled clinical trial

    DEFF Research Database (Denmark)

    Beier-Holgersen, R; Brandstrup, B

    2012-01-01

    The aim of this study was to discover if the cellular immunological response is different in patients receiving early postoperative enteral nutrition compared to patients who only receive "water".......The aim of this study was to discover if the cellular immunological response is different in patients receiving early postoperative enteral nutrition compared to patients who only receive "water"....

  9. Proteomics and its applications to aquaculture in China: infection, immunity, and interaction of aquaculture hosts with pathogens.

    Science.gov (United States)

    Peng, Xuan-Xian

    2013-01-01

    China is the largest fishery producer worldwide in term of its aquaculture output, and plays leading and decisive roles in international aquaculture development. To improve aquaculture output further and promote aquaculture business development, infectious diseases and immunity of fishes and other aquaculture species must be studied. In this regard, aquaculture proteomics has been widely carried out in China to get a better understanding of aquaculture host immunity and microbial pathogenesis as well as host-pathogen interactions, and to identify novel disease targets and vaccine candidates for therapeutic interventions. These proteomics studies include development of novel methods, assays, and advanced concepts in order to characterize proteomics mechanisms of host innate immune defense and microbial pathogenesis. This review article summarizes some recently published technical approaches and their applications to aquaculture proteomics with an emphasis on the responses of aquaculture animals to bacteria, viruses, and other aqua-environmental stresses, and development of broadly cross-protective vaccine candidates. The reviewed articles are those that have been published in international peer reviewed journals. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Comparison of intraoperative conditions and postoperative inflammatory response and immune response between patients with common bile duct stones undergoing ESBD and EST

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    Kun Zh

    2016-08-01

    Full Text Available Objective: To analyze the differences in intraoperative conditions and postoperative inflammatory response and immune response levels in patients with common bile duct stones undergoing ESBD and EST treatment. Methods: A total of 565 patients with common bile duct stones who underwent ERCP treatment in our hospital from January 2013 to December 2015 were included in the study, patients’ treatment and testing results were analyzed retrospectively, and then patients were divided into the observation group 300 cases that received ESBD treatment and control group 265 cases that received EST treatment. Differences in intraoperative stress levels as well as postoperative inflammation, nutrition-related index and immune response levels were compared between two groups. Results: Intraoperative N, Cor, C-P and NK cell levels of observation group were lower than those of control group, and FT3 level was higher than that of control group; postoperative inflammation-related factors such as IL-6, CRP, PCT, CA19-9 and CEA levels were lower than those of control group, protein nutrition indexes such as TP, Alb, PA, TRF and RBP values were higher than those of control group, and immune indexes such as CD4+, CD4+/CD8+, IgA, IgM and IgG levels were higher than those of control group while CD8+ level was lower than that of control group. Conclusion: ESBD for the treatment of patients with common bile duct stones is better than EST treatment in reducing surgical stress, optimizing postoperative physical status and other aspects.

  11. Small non-coding RNAs: new insights in modulation of host immune response by intracellular bacterial pathogens

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    Waqas Ahmed

    2016-10-01

    Full Text Available Pathogenic bacteria possess intricate regulatory networks that temporally control the production of virulence factors, and enable the bacteria to survive and proliferate within host cell. Small non-coding RNAs (sRNAs have been identified as important regulators of gene expression in diverse biological contexts. Recent research has shown bacterial sRNAs involved in growth and development, cell proliferation, differentiation, metabolism, cell signaling and immune response through regulating protein–protein interactions or via their ability to base pair with RNA and DNA. In this review, we provide a brief overview of mechanism of action employed by immune-related sRNAs, their known functions in immunity, and how they can be integrated into regulatory circuits that govern virulence, which will facilitates to understand pathogenesis and the development of novel, more effective therapeutic approaches to treat infections caused by intracellular bacterial pathogens.

  12. STSV2 as a Model Crenarchaeal Virus for Studying Virus-Host Interactions and CRISPR-Cas Adaptive Immunity

    DEFF Research Database (Denmark)

    León Sobrino, Carlos

    , the archaea harbour their own viruses, which constitute an extraordinarily diverse group with exotic morphologies and unique features. Prokaryotes possess a variety of defence mechanisms. The CRISPR-Cas adaptive immune system is of great importance for archaea –84% of them possess it, compared to 45...... generate immune memory by inserting in its own genome short invader-derived DNA fragments forming a database –the CRISPR locus. Little was known about this system until recent years, and the generation of immune memory has been the most elusive step. In this work, the interactions of the spindle......-shaped monocaudavirus STSV2 and its host Sulfolobus islandicus REY15A were studied. This interaction produced, after several days, de novo CRISPR adaptation – that is, without any previous memory that can act as a trigger. We employed transcriptome sequencing to characterise the long-term progression...

  13. Immunobiotics for the Bovine Host: Their Interaction with Intestinal Epithelial Cells and Their Effect on Antiviral Immunity

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    Julio Villena

    2018-03-01

    Full Text Available The scientific community has reported several cases of microbes that exhibit elevated rates of antibiotic resistance in different regions of the planet. Due to this emergence of antimicrobial resistant microorganisms, the use of antibiotics as promoters of livestock animals’ growth is being banned in most countries around the world. One of the challenges of agricultural immunology therefore is to find alternatives by modulating the immune system of animals in drug-independent safe food production systems. In this regard, in an effort to supplant antibiotics from bovine feeds, several alternatives were proposed including the use of immunomodulatory probiotics (immunobiotics. The purpose of this review is to provide an update of the status of the modulation of intestinal antiviral innate immunity of the bovine host by immunobiotics, and the beneficial impact of immunobiotics on viral infections, focused on intestinal epithelial cells (IECs. The results of our group, which demonstrate the capacity of immunobiotic strains to beneficially modulate Toll-like receptor 3-triggered immune responses in bovine IECs and improve the resistance to viral infections, are highlighted. This review provides comprehensive information on the innate immune response of bovine IECs against virus, which can be further investigated for the development of strategies aimed to improve defenses in the bovine host.

  14. Human and Animal Isolates of Yersinia enterocolitica Show Significant Serotype-Specific Colonization and Host-Specific Immune Defense Properties

    Science.gov (United States)

    Schaake, Julia; Kronshage, Malte; Uliczka, Frank; Rohde, Manfred; Knuuti, Tobias; Strauch, Eckhard; Fruth, Angelika; Wos-Oxley, Melissa

    2013-01-01

    Yersinia enterocolitica is a human pathogen that is ubiquitous in livestock, especially pigs. The bacteria are able to colonize the intestinal tract of a variety of mammalian hosts, but the severity of induced gut-associated diseases (yersiniosis) differs significantly between hosts. To gain more information about the individual virulence determinants that contribute to colonization and induction of immune responses in different hosts, we analyzed and compared the interactions of different human- and animal-derived isolates of serotypes O:3, O:5,27, O:8, and O:9 with murine, porcine, and human intestinal cells and macrophages. The examined strains exhibited significant serotype-specific cell binding and entry characteristics, but adhesion and uptake into different host cells were not host specific and were independent of the source of the isolate. In contrast, survival and replication within macrophages and the induced proinflammatory response differed between murine, porcine, and human macrophages, suggesting a host-specific immune response. In fact, similar levels of the proinflammatory cytokine macrophage inflammatory protein 2 (MIP-2) were secreted by murine bone marrow-derived macrophages with all tested isolates, but the equivalent interleukin-8 (IL-8) response of porcine bone marrow-derived macrophages was strongly serotype specific and considerably lower in O:3 than in O:8 strains. In addition, all tested Y. enterocolitica strains caused a considerably higher level of secretion of the anti-inflammatory cytokine IL-10 by porcine than by murine macrophages. This could contribute to limiting the severity of the infection (in particular of serotype O:3 strains) in pigs, which are the primary reservoir of Y. enterocolitica strains pathogenic to humans. PMID:23959720

  15. T Lymphocyte Immunity in Host Defence against Chlamydia trachomatis and Its Implication for Vaccine Development

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    X Yang

    1998-01-01

    Full Text Available Chlamydia trachomatis is an obligate intracellular bacterial pathogen that causes several significant human infectious diseases, including trachoma, urethritis, cervicitis and salpingitis, and is an important cofactor for transmission of human immunodeficiency virus. Until very recently, over three decades of research effort aimed at developing a C trachomatis vaccine had failed, due mainly to the lack of a precise understanding of the mechanisms for protective immunity. Although most studies concerning protective immunity to C trachomatis have focused on humoral immune responses, recent studies have clearly shown that T helper-1 (Th1-like CD4 T cell-mediated immune responses play the dominant role in protective immunity. These studies suggest a paradigm for chlamydial immunity and pathology based on the concept of heterogeneity (Th1/Th2 in CD4 T cell immune responses. This concept for chlamydial immunity offers a rational template on which to base renewed efforts for development of a chlamydial vaccine that targets the induction of cell-mediated Th1 immune responses.

  16. Host immunity, nutrition and coinfection alter longitudinal infection patterns of schistosomes in a free ranging African buffalo population.

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    Brianna R Beechler

    2017-12-01

    Full Text Available Schistosomes are trematode parasites of global importance, causing infections in millions of people, livestock, and wildlife. Most studies on schistosomiasis, involve human subjects; as such, there is a paucity of longitudinal studies investigating parasite dynamics in the absence of intervention. As a consequence, despite decades of research on schistosomiasis, our understanding of its ecology in natural host populations is centered around how environmental exposure and acquired immunity influence acquisition of parasites, while very little is known about the influence of host physiology, coinfection and clearance in the absence of drug treatment. We used a 4-year study in free-ranging African buffalo to investigate natural schistosome dynamics. We asked (i what are the spatial and temporal patterns of schistosome infections; (ii how do parasite burdens vary over time within individual hosts; and (iii what host factors (immunological, physiological, co-infection and environmental factors (season, location explain patterns of schistosome acquisition and loss in buffalo? Schistosome infections were common among buffalo. Microgeographic structure explained some variation in parasite burdens among hosts, indicating transmission hotspots. Overall, parasite burdens ratcheted up over time; however, gains in schistosome abundance in the dry season were partially offset by losses in the wet season, with some hosts demonstrating complete clearance of infection. Variation among buffalo in schistosome loss was associated with immunologic and nutritional factors, as well as co-infection by the gastrointestinal helminth Cooperia fuelleborni. Our results demonstrate that schistosome infections are surprisingly dynamic in a free-living mammalian host population, and point to a role for host factors in driving variation in parasite clearance, but not parasite acquisition which is driven by seasonal changes and spatial habitat utilization. Our study illustrates

  17. Stealth proteins: in silico identification of a novel protein family rendering bacterial pathogens invisible to host immune defense.

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    Peter Sperisen

    2005-11-01

    Full Text Available There are a variety of bacterial defense strategies to survive in a hostile environment. Generation of extracellular polysaccharides has proved to be a simple but effective strategy against the host's innate immune system. A comparative genomics approach led us to identify a new protein family termed Stealth, most likely involved in the synthesis of extracellular polysaccharides. This protein family is characterized by a series of domains conserved across phylogeny from bacteria to eukaryotes. In bacteria, Stealth (previously characterized as SacB, XcbA, or WefC is encoded by subsets of strains mainly colonizing multicellular organisms, with evidence for a protective effect against the host innate immune defense. More specifically, integrating all the available information about Stealth proteins in bacteria, we propose that Stealth is a D-hexose-1-phosphoryl transferase involved in the synthesis of polysaccharides. In the animal kingdom, Stealth is strongly conserved across evolution from social amoebas to simple and complex multicellular organisms, such as Dictyostelium discoideum, hydra, and human. Based on the occurrence of Stealth in most Eukaryotes and a subset of Prokaryotes together with its potential role in extracellular polysaccharide synthesis, we propose that metazoan Stealth functions to regulate the innate immune system. Moreover, there is good reason to speculate that the acquisition and spread of Stealth could be responsible for future epidemic outbreaks of infectious diseases caused by a large variety of eubacterial pathogens. Our in silico identification of a homologous protein in the human host will help to elucidate the causes of Stealth-dependent virulence. At a more basic level, the characterization of the molecular and cellular function of Stealth proteins may shed light on fundamental mechanisms of innate immune defense against microbial invasion.

  18. Stealth Proteins: In Silico Identification of a Novel Protein Family Rendering Bacterial Pathogens Invisible to Host Immune Defense.

    Directory of Open Access Journals (Sweden)

    2005-11-01

    Full Text Available There are a variety of bacterial defense strategies to survive in a hostile environment. Generation of extracellular polysaccharides has proved to be a simple but effective strategy against the host's innate immune system. A comparative genomics approach led us to identify a new protein family termed Stealth, most likely involved in the synthesis of extracellular polysaccharides. This protein family is characterized by a series of domains conserved across phylogeny from bacteria to eukaryotes. In bacteria, Stealth (previously characterized as SacB, XcbA, or WefC is encoded by subsets of strains mainly colonizing multicellular organisms, with evidence for a protective effect against the host innate immune defense. More specifically, integrating all the available information about Stealth proteins in bacteria, we propose that Stealth is a D-hexose-1-phosphoryl transferase involved in the synthesis of polysaccharides. In the animal kingdom, Stealth is strongly conserved across evolution from social amoebas to simple and complex multicellular organisms, such as Dictyostelium discoideum, hydra, and human. Based on the occurrence of Stealth in most Eukaryotes and a subset of Prokaryotes together with its potential role in extracellular polysaccharide synthesis, we propose that metazoan Stealth functions to regulate the innate immune system. Moreover, there is good reason to speculate that the acquisition and spread of Stealth could be responsible for future epidemic outbreaks of infectious diseases caused by a large variety of eubacterial pathogens. Our in silico identification of a homologous protein in the human host will help to elucidate the causes of Stealth-dependent virulence. At a more basic level, the characterization of the molecular and cellular function of Stealth proteins may shed light on fundamental mechanisms of innate immune defense against microbial invasion.

  19. Bacteria modulate the CD8+ T cell epitope repertoire of host cytosol-exposed proteins to manipulate the host immune response.

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    Yaakov Maman

    2011-10-01

    Full Text Available The main adaptive immune response to bacteria is mediated by B cells and CD4+ T-cells. However, some bacterial proteins reach the cytosol of host cells and are exposed to the host CD8+ T-cells response. Both gram-negative and gram-positive bacteria can translocate proteins to the cytosol through type III and IV secretion and ESX-1 systems, respectively. The translocated proteins are often essential for the bacterium survival. Once injected, these proteins can be degraded and presented on MHC-I molecules to CD8+ T-cells. The CD8+ T-cells, in turn, can induce cell death and destroy the bacteria's habitat. In viruses, escape mutations arise to avoid this detection. The accumulation of escape mutations in bacteria has never been systematically studied. We show for the first time that such mutations are systematically present in most bacteria tested. We combine multiple bioinformatic algorithms to compute CD8+ T-cell epitope libraries of bacteria with secretion systems that translocate proteins to the host cytosol. In all bacteria tested, proteins not translocated to the cytosol show no escape mutations in their CD8+ T-cell epitopes. However, proteins translocated to the cytosol show clear escape mutations and have low epitope densities for most tested HLA alleles. The low epitope densities suggest that bacteria, like viruses, are evolutionarily selected to ensure their survival in the presence of CD8+ T-cells. In contrast with most other translocated proteins examined, Pseudomonas aeruginosa's ExoU, which ultimately induces host cell death, was found to have high epitope density. This finding suggests a novel mechanism for the manipulation of CD8+ T-cells by pathogens. The ExoU effector may have evolved to maintain high epitope density enabling it to efficiently induce CD8+ T-cell mediated cell death. These results were tested using multiple epitope prediction algorithms, and were found to be consistent for most proteins tested.

  20. CD19 CAR T Cells Expressing IL-12 Eradicate Lymphoma in Fully Lymphoreplete Mice through Induction of Host Immunity

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    Gray Kueberuwa

    2018-03-01

    Full Text Available Chimeric antigen receptor (CAR T cell therapy represents a significant advancement in cancer therapy. Larger studies have shown ∼90% complete remission rates against chemoresistant and/or refractory CD19+ leukemia or lymphoma. Effective CAR T cell therapy is highly dependent on lymphodepleting preconditioning, which is achieved through chemotherapy or radiotherapy that carries with it significant toxicities. These can exclude patients of low performance status. In order to overcome the need for preconditioning, we constructed fully mouse first and second generation anti-murine CD19 CARs with or without interleukin-12 (IL-12 secretion. To test these CARs, we established a mouse model to reflect the human situation without preconditioning. Murine second generation CAR T cells expressing IL-12 were capable of eradicating established B cell lymphoma with a long-term survival rate of ∼25%. We believe this to be the first study in a truly lymphoreplete model. We provide evidence that IL-12-expressing CAR T cells not only directly kill target CD19+ cells, but also recruit host immune cells to an anti-cancer immune response. This finding is critical because lymphodepletion regimens required for the success of current CAR T cell technology eliminate host immune cells whose anti-cancer activity could otherwise be harnessed by strategies such as IL-12-secreting CAR T cells. Keywords: CD19 CAR T cells, IL-12, immunotherapy, chimeric antigen receptor, adoptive cellular therapy, lymphoma, B cell malignancies, TRUCKs, pre-conditioning

  1. Serratia marcescens Induces Apoptotic Cell Death in Host Immune Cells via a Lipopolysaccharide- and Flagella-dependent Mechanism*

    Science.gov (United States)

    Ishii, Kenichi; Adachi, Tatsuo; Imamura, Katsutoshi; Takano, Shinya; Usui, Kimihito; Suzuki, Kazushi; Hamamoto, Hiroshi; Watanabe, Takeshi; Sekimizu, Kazuhisa

    2012-01-01

    Injection of Serratia marcescens into the blood (hemolymph) of the silkworm, Bombyx mori, induced the activation of c-Jun NH2-terminal kinase (JNK), followed by caspase activation and apoptosis of blood cells (hemocytes). This process impaired the innate immune response in which pathogen cell wall components, such as glucan, stimulate hemocytes, leading to the activation of insect cytokine paralytic peptide. S. marcescens induced apoptotic cell death of silkworm hemocytes and mouse peritoneal macrophages in vitro. We searched for S. marcescens transposon mutants with attenuated ability to induce apoptosis of silkworm hemocytes. Among the genes identified, disruption mutants of wecA (a gene involved in lipopolysaccharide O-antigen synthesis), and flhD and fliR (essential genes in flagella synthesis) showed reduced motility and impaired induction of mouse macrophage cell death. These findings suggest that S. marcescens induces apoptosis of host immune cells via lipopolysaccharide- and flagella-dependent motility, leading to the suppression of host innate immunity. PMID:22859304

  2. Recombinant Marburg viruses containing mutations in the IID region of VP35 prevent inhibition of Host immune responses.

    Science.gov (United States)

    Albariño, César G; Wiggleton Guerrero, Lisa; Spengler, Jessica R; Uebelhoer, Luke S; Chakrabarti, Ayan K; Nichol, Stuart T; Towner, Jonathan S

    2015-02-01

    Previous in vitro studies have demonstrated that Ebola and Marburg virus (EBOV and MARV) VP35 antagonize the host cell immune response. Moreover, specific mutations in the IFN inhibitory domain (IID) of EBOV and MARV VP35 that abrogate their interaction with virus-derived dsRNA, lack the ability to inhibit the host immune response. To investigate the role of MARV VP35 in the context of infectious virus, we used our reverse genetics system to generate two recombinant MARVs carrying specific mutations in the IID region of VP35. Our data show that wild-type and mutant viruses grow to similar titers in interferon deficient cells, but exhibit attenuated growth in interferon-competent cells. Furthermore, in contrast to wild-type virus, both MARV mutants were unable to inhibit expression of various antiviral genes. The MARV VP35 mutants exhibit similar phenotypes to those previously described for EBOV, suggesting the existence of a shared immune-modulatory strategy between filoviruses. Published by Elsevier Inc.

  3. Effect of perioperative application of L-asrginine combined with intacted protein compound preparations on postoperative antitumor immunity and tumor load in patients with gastric cancer

    Directory of Open Access Journals (Sweden)

    Xiu-Lan Jiang

    2016-10-01

    Full Text Available Objective: To analyze the effect of perioperative application of L-arginine combined with intacted protein compound preparations on postoperative antitumor immunity and tumor load in patients with gastric cancer. Methods: A total of 68 patients with gastric cancer received radical operation, and according to different perioperative nutrition intervention, they were divided into control group (normal glucose saline enteral nutrition and observation group (L-arginine combined with intacted protein compound preparations enteral nutrition by half. Postoperative short-term antitumor immune cell levels and serum levels of illness-related indexes, nutrition and inflammation indexes of two groups were detected, patients were followed up for 3 years and the gastric stump MRI changes were observed. Results: Venous blood CD4+ T lymphocyte level and CD4+ /CD8+ ratio of observation group 3 months after treatment were higher than those of control group while CD8+ T lymphocyte and Treg cell levels were lower than those of control group; serum Pentraxin-3, CYFRA21-1, TTF-1 and HE4 levels were lower than those of control group; ALB, PA and IL-2 levels were higher than those of control group while IL-6 and IL-10 levels were lower than those of control group (P<0.05. Gastric stump MRI images 3 years after operation were significantly different between two groups. Conclusions: Perioperative application of L-arginine combined with intacted protein compound preparations can optimize postoperative immune and nutritional state in patients with gastric cancer, and it also has positive effect on reducing the incidence of long-term gastric stump carcinoma and other aspects.

  4. The Bacterial Second Messenger Cyclic di-GMP Regulates Brucella Pathogenesis and Leads to Altered Host Immune Response.

    Science.gov (United States)

    Khan, Mike; Harms, Jerome S; Marim, Fernanda M; Armon, Leah; Hall, Cherisse L; Liu, Yi-Ping; Banai, Menachem; Oliveira, Sergio C; Splitter, Gary A; Smith, Judith A

    2016-12-01

    Brucella species are facultative intracellular bacteria that cause brucellosis, a chronic debilitating disease significantly impacting global health and prosperity. Much remains to be learned about how Brucella spp. succeed in sabotaging immune host cells and how Brucella spp. respond to environmental challenges. Multiple types of bacteria employ the prokaryotic second messenger cyclic di-GMP (c-di-GMP) to coordinate responses to shifting environments. To determine the role of c-di-GMP in Brucella physiology and in shaping host-Brucella interactions, we utilized c-di-GMP regulatory enzyme deletion mutants. Our results show that a ΔbpdA phosphodiesterase mutant producing excess c-di-GMP displays marked attenuation in vitro and in vivo during later infections. Although c-di-GMP is known to stimulate the innate sensor STING, surprisingly, the ΔbpdA mutant induced a weaker host immune response than did wild-type Brucella or the low-c-di-GMP guanylate cyclase ΔcgsB mutant. Proteomics analysis revealed that c-di-GMP regulates several processes critical for virulence, including cell wall and biofilm formation, nutrient acquisition, and the type IV secretion system. Finally, ΔbpdA mutants exhibited altered morphology and were hypersensitive to nutrient-limiting conditions. In summary, our results indicate a vital role for c-di-GMP in allowing Brucella to successfully navigate stressful and shifting environments to establish intracellular infection. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  5. The impact of a diet with fructan-rich chicory roots on Oesophagostomum dentatum worm population dynamics and host immune responses in pigs

    DEFF Research Database (Denmark)

    Thamsborg, Stig Millan; Mejer, Helena; Skovgaard, Kerstin

    Oesophagostomum infections in pigs persist for months. We hypothesized that feeding fructans (dried chicory roots) may improve immunity and facilitate worm expulsion. We therefore examined the effects of long-term chicory on O. dentatum population dynamics and host immune responses. Methods: Seve...

  6. Increased Plasma Levels of Danger-Associated Molecular Patterns Are Associated With Immune Suppression and Postoperative Infections in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

    Directory of Open Access Journals (Sweden)

    Guus P. Leijte

    2018-04-01

    Full Text Available IntroductionDanger-associated molecular patterns (DAMPs can elicit immune responses and may subsequently induce an immune-suppressed state. Previous work showed that increased plasma levels of DAMPs are associated with immune suppression and increased susceptibility toward infections in trauma patients. Like trauma, major surgical procedures, such as cytoreductive surgery (CRS combined with hyperthermic intraperitoneal chemotherapy (HIPEC, are also thought to cause profound DAMP release. Furthermore, the incidence of postoperative infections in these patients, ranging from 10 to 36%, is very high compared to that observed in patients undergoing other major surgical procedures. We hypothesized that the double hit of surgical trauma (CRS in combination with HIPEC causes excessive DAMP release, which in turn contributes to the development of immune suppression. To investigate this, we assessed DAMP release in patients undergoing CRS-HIPEC, and investigated its relationship with immune suppression and postoperative infections.MethodsIn 20 patients undergoing CRS-HIPEC, blood was obtained at five time points: just before surgery (baseline, after CRS, after HIPEC, at ICU admission, and 1 day after surgery. Circulating levels of DAMPs [heat shock protein (HSP70, high mobility group box (HMGB1, S100A12, S100A8/S100A9, nuclear (nDNA, mitochondrial (mtDNA, lactate dehydrogenase (LDH, a marker of unscheduled cell death], and cytokines [tumor necrosis factor (TNFα, IL-6, IL-8, IL-10, macrophage inflammatory protein (MIP-1α, MIP-1β, and MCP-1] were measured. The extent of immune suppression was determined by measuring HLA-DR gene expression and ex vivo leukocytic cytokine production capacity.ResultsPlasma levels of DAMPs (maximum fold increases of HSP70: 2.1 [1.5–2.8], HMGB1: 5.9 [3.2–9.8], S100A8/S100A9: 3.6 [1.8–5.6], S100A12: 2.6 [1.8–4.3], nDNA 3.9 [1.0–10.8], LDH 1.7 [1.2–2.5], and all measured cytokines increased profoundly following

  7. Impact of Enterobius vermicularis infection and mebendazole treatment on intestinal microbiota and host immune response

    OpenAIRE

    Yang, Chin-An; Liang, Chao; Lin, Chia-Li; Hsiao, Chiung-Tzu; Peng, Ching-Tien; Lin, Hung-Chih; Chang, Jan-Gowth

    2017-01-01

    Background Previous studies on the association of enterobiasis and chronic inflammatory diseases have revealed contradictory results. The interaction of Enterobius vermicularis infection in particular with gut microbiota and induced immune responses has never been thoroughly examined. Methodology/Findings In order to answer the question of whether exposure to pinworm and mebendazole can shift the intestinal microbial composition and immune responses, we recruited 109 (30 pinworm-negative, 79 ...

  8. Necrotizing herpetic retinopathies. A spectrum of herpes virus-induced diseases determined by the immune state of the host.

    Science.gov (United States)

    Guex-Crosier, Y; Rochat, C; Herbort, C P

    1997-12-01

    Necrotizing herpetic retinopathies (NHR), a new spectrum of diseases induced by viruses of the herpes family (herpes simplex virus, varicella-zoster virus and cytomegalovirus), includes acute retinal necrosis (ARN) occurring in apparently immunocompetent patients and progressive outer retinal necrosis (PORN) described in severely immuno-compromised patients. Signs of impaired cellular immunity were seen in 16% of ARN patients in a review of 216 reported cases, indicating that immune dysfunction is not only at the origin of PORN but might also be at the origin of ARN. The aim of this study was to correlate clinical findings in NHR patients with their immunologic parameters. Charts from patients with the diagnosis of ARN or PORN seen from 1990 to 1995 were reviewed. Clinical characteristics and disease patterns were correlated with immunological parameters taking into account CD4 lymphocyte rate in AIDS patients and blood-lymphocyte subpopulation determination by flow cytometry, cutaneous delayed type hypersensitivity testing and lymphocytic proliferation rate to seven antigens in HIV-negative patients. During the period considered, 11 patients and 7 patients fulfilled the criteria of ARN and PORN respectively. Immune dysfunctions were identified in most patients. Mild type of ARN and classical ARN were associated with discrete immune dysfunctions, ARN with features of PORN was seen in more immunodepressed patients and classical PORN was always seen in severely immunodepressed HIV patients. Our findings suggest that NHR is a continuous spectrum of diseases induced by herpes viruses, whose clinical expression depends on the immune state of the host going from mild or classical ARN at one end in patients with non-detectable or slight immune dysfunction to PORN in severely immunodepressed patients at the other end and with intermediary forms between these extremes.

  9. Evidence for significant influence of host immunity on changes in differential blood count during malaria.

    Science.gov (United States)

    Berens-Riha, Nicole; Kroidl, Inge; Schunk, Mirjam; Alberer, Martin; Beissner, Marcus; Pritsch, Michael; Kroidl, Arne; Fröschl, Günter; Hanus, Ingrid; Bretzel, Gisela; von Sonnenburg, Frank; Nothdurft, Hans Dieter; Löscher, Thomas; Herbinger, Karl-Heinz

    2014-04-23

    Malaria has been shown to change blood counts. Recently, a few studies have investigated the alteration of the peripheral blood monocyte-to-lymphocyte count ratio (MLCR) and the neutrophil-to-lymphocyte count ratio (NLCR) during infection with Plasmodium falciparum. Based on these findings this study investigates the predictive values of blood count alterations during malaria across different sub-populations. Cases and controls admitted to the Department of Infectious Diseases and Tropical Medicine from January 2000 through December 2010 were included in this comparative analysis. Blood count values and other variables at admission controlled for age, gender and immune status were statistically investigated. The study population comprised 210 malaria patients, infected with P. falciparum (68%), Plasmodium vivax (21%), Plasmodium ovale (7%) and Plasmodium malariae (4%), and 210 controls. A positive correlation of parasite density with NLCR and neutrophil counts, and a negative correlation of parasite density with thrombocyte, leucocyte and lymphocyte counts were found. An interaction with semi-immunity was observed; ratios were significantly different in semi-immune compared to non-immune patients (P value of the ratios was fair but limited. However, these changes were less pronounced in patients with semi-immunity. The ratios might constitute easily applicable surrogate biomarkers for immunity.

  10. Serratia marcescens Suppresses Host Cellular Immunity via the Production of an Adhesion-inhibitory Factor against Immunosurveillance Cells*

    Science.gov (United States)

    Ishii, Kenichi; Adachi, Tatsuo; Hamamoto, Hiroshi; Sekimizu, Kazuhisa

    2014-01-01

    Injection of a culture supernatant of Serratia marcescens into the bloodstream of the silkworm Bombyx mori increased the number of freely circulating immunosurveillance cells (hemocytes). Using a bioassay with live silkworms, serralysin metalloprotease was purified from the culture supernatant and identified as the factor responsible for this activity. Serralysin inhibited the in vitro attachment of both silkworm hemocytes and murine peritoneal macrophages. Incubation of silkworm hemocytes or murine macrophages with serralysin resulted in degradation of the cellular immune factor BmSPH-1 or calreticulin, respectively. Furthermore, serralysin suppressed in vitro phagocytosis of bacteria by hemocytes and in vivo bacterial clearance in silkworms. Disruption of the ser gene in S. marcescens attenuated its host killing ability in silkworms and mice. These findings suggest that serralysin metalloprotease secreted by S. marcescens suppresses cellular immunity by decreasing the adhesive properties of immunosurveillance cells, thereby contributing to bacterial pathogenesis. PMID:24398686

  11. Serratia marcescens suppresses host cellular immunity via the production of an adhesion-inhibitory factor against immunosurveillance cells.

    Science.gov (United States)

    Ishii, Kenichi; Adachi, Tatsuo; Hamamoto, Hiroshi; Sekimizu, Kazuhisa

    2014-02-28

    Injection of a culture supernatant of Serratia marcescens into the bloodstream of the silkworm Bombyx mori increased the number of freely circulating immunosurveillance cells (hemocytes). Using a bioassay with live silkworms, serralysin metalloprotease was purified from the culture supernatant and identified as the factor responsible for this activity. Serralysin inhibited the in vitro attachment of both silkworm hemocytes and murine peritoneal macrophages. Incubation of silkworm hemocytes or murine macrophages with serralysin resulted in degradation of the cellular immune factor BmSPH-1 or calreticulin, respectively. Furthermore, serralysin suppressed in vitro phagocytosis of bacteria by hemocytes and in vivo bacterial clearance in silkworms. Disruption of the ser gene in S. marcescens attenuated its host killing ability in silkworms and mice. These findings suggest that serralysin metalloprotease secreted by S. marcescens suppresses cellular immunity by decreasing the adhesive properties of immunosurveillance cells, thereby contributing to bacterial pathogenesis.

  12. The roles of host and pathogen factors and the innate immune response in the pathogenesis of Clostridium difficile infection

    Science.gov (United States)

    Sun, Xingmin; Hirota, Simon A.

    2014-01-01

    Clostridium difficile (C. difficile) is the most common cause of nosocomial antibiotic-associated diarrhea and the etiologic agent of pseudomembranous colitis. The clinical manifestation of Clostridium difficile infection (CDI) is highly variable, from asymptomatic carriage, to mild self-limiting diarrhea, to the more severe pseudomembranous colitis. Furthermore, in extreme cases, colonic inflammation and tissue damage can lead to toxic megacolon, a condition requiring surgical intervention. C. difficile expresses two key virulence factors; the exotoxins, toxin A (TcdA) and toxin B (TcdB), which are glucosyltransferases that target host-cell monomeric GTPases. In addition, some hypervirulent strains produce a third toxin, binary toxin or C. difficile transferase (CDT), which may contribute to the pathogenesis of CDI. More recently, other factors such as surface layer proteins (SLPs) and flagellin have also been linked to the inflammatory responses observed in CDI. Although the adaptive immune response can influence the severity of CDI, the innate immune responses to C. difficile and its toxins play crucial roles in CDI onset, progression, and overall prognosis. Despite this, the innate immune responses in CDI have drawn relatively little attention from clinical researchers. Targeting these responses may prove useful clinically as adjuvant therapies, especially in refractory and/or recurrent CDI. This review will focus on recent advances in our understanding of how C. difficile and its toxins modulate innate immune responses that contribute to CDI pathogenesis. PMID:25242213

  13. Host-pathogen interactions between the human innate immune system and Candida albicans - Understanding and modeling defense and evasion strategies

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    Sybille eDühring

    2015-06-01

    Full Text Available The diploid, polymorphic yeast Candida albicans is one of the most important humanpathogenic fungi. C. albicans can grow, proliferate and coexist as a commensal on or within thehuman host for a long time. Alterations in the host environment, however, can render C. albicansvirulent. In this review, we describe the immunological cross-talk between C. albicans and thehuman innate immune system. We give an overview in form of pairs of human defense strategiesincluding immunological mechanisms as well as general stressors such as nutrient limitation,pH, fever etc. and the corresponding fungal response and evasion mechanisms. FurthermoreComputational Systems Biology approaches to model and investigate these complex interactionare highlighted with a special focus on game-theoretical methods and agent-based models. Anoutlook on interesting questions to be tackled by Systems Biology regarding entangled defenseand evasion mechanisms is given.

  14. Maintenance of host leukocytes in peripheral immune compartments following lethal irradiation and bone marrow reconstitution: implications for graft versus host disease.

    Science.gov (United States)

    Staley, Elizabeth M; Tanner, Scott M; Daft, Joseph G; Stanus, Andrea L; Martin, Steven M; Lorenz, Robin G

    2013-03-01

    Bone marrow reconstitution is utilized as a tool for disease treatment and as a research technique to elucidate the function of bone marrow derived cells. Clinically successful engraftment is indicated by the development of a functioning immune repertoire. In research, reconstitution is considered successful if >85% of splenic leukocytes are of donor origins. Previous work suggests that splenic reconstitution may not be indicative of reconstitution in the mucosa. We sought to evaluate mucosal reconstitution in animals following a standard bone marrow eradication and reconstitution technique. Bone marrow was harvested from adult B6.SJL donor mice (CD45.1) and injected via either the retro-orbital or intraperitoneal route into lethally irradiated B6 (CD45.2) adult or neonatal recipients respectively. The expression of CD45 by flow cytometry was used to calculate reconstitution with respect to immune compartment and cell type. In reconstituted adult animals 93.2±1.5% of splenic leukocytes expressed the donor CD45.1 antigen thus meeting the standard definition of reconstitution, however only 58.6±13.6% of intestinal lamina propria lymphocytes and 52.4±16.0% of intestinal intraepithelial lymphocytes were of donor origin, confirming splenic reconstitution fails to represent peripheral immune reconstitution. T-cells in the gastrointestinal tract are the most poorly reconstituted, while B-cells appear to be almost universally replaced by donor cells. The inadequate mucosal reconstitution was not corrected by evaluating later time points or by performing the bone marrow transfer during the neonatal period. This demonstration that substantial host T-cells remain in the intestinal mucosa after a "successful" bone marrow transplantation should cause a re-evaluation of data from research bone marrow chimera experiments, as well as the mechanisms for complications after clinical bone marrow transplantation. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Insight into bacterial virulence mechanisms against host immune response via the Yersinia pestis-human protein-protein interaction network.

    Science.gov (United States)

    Yang, Huiying; Ke, Yuehua; Wang, Jian; Tan, Yafang; Myeni, Sebenzile K; Li, Dong; Shi, Qinghai; Yan, Yanfeng; Chen, Hui; Guo, Zhaobiao; Yuan, Yanzhi; Yang, Xiaoming; Yang, Ruifu; Du, Zongmin

    2011-11-01

    A Yersinia pestis-human protein interaction network is reported here to improve our understanding of its pathogenesis. Up to 204 interactions between 66 Y. pestis bait proteins and 109 human proteins were identified by yeast two-hybrid assay and then combined with 23 previously published interactions to construct a protein-protein interaction network. Topological analysis of the interaction network revealed that human proteins targeted by Y. pestis were significantly enriched in the proteins that are central in the human protein-protein interaction network. Analysis of this network showed that signaling pathways important for host immune responses were preferentially targeted by Y. pestis, including the pathways involved in focal adhesion, regulation of cytoskeleton, leukocyte transendoepithelial migration, and Toll-like receptor (TLR) and mitogen-activated protein kinase (MAPK) signaling. Cellular pathways targeted by Y. pestis are highly relevant to its pathogenesis. Interactions with host proteins involved in focal adhesion and cytoskeketon regulation pathways could account for resistance of Y. pestis to phagocytosis. Interference with TLR and MAPK signaling pathways by Y. pestis reflects common characteristics of pathogen-host interaction that bacterial pathogens have evolved to evade host innate immune response by interacting with proteins in those signaling pathways. Interestingly, a large portion of human proteins interacting with Y. pestis (16/109) also interacted with viral proteins (Epstein-Barr virus [EBV] and hepatitis C virus [HCV]), suggesting that viral and bacterial pathogens attack common cellular functions to facilitate infections. In addition, we identified vasodilator-stimulated phosphoprotein (VASP) as a novel interaction partner of YpkA and showed that YpkA could inhibit in vitro actin assembly mediated by VASP.

  16. Multivariate statistical analyses demonstrate unique host immune responses to single and dual lentiviral infection.

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    Sunando Roy

    2009-10-01

    Full Text Available Feline immunodeficiency virus (FIV and human immunodeficiency virus (HIV are recently identified lentiviruses that cause progressive immune decline and ultimately death in infected cats and humans. It is of great interest to understand how to prevent immune system collapse caused by these lentiviruses. We recently described that disease caused by a virulent FIV strain in cats can be attenuated if animals are first infected with a feline immunodeficiency virus derived from a wild cougar. The detailed temporal tracking of cat immunological parameters in response to two viral infections resulted in high-dimensional datasets containing variables that exhibit strong co-variation. Initial analyses of these complex data using univariate statistical techniques did not account for interactions among immunological response variables and therefore potentially obscured significant effects between infection state and immunological parameters.Here, we apply a suite of multivariate statistical tools, including Principal Component Analysis, MANOVA and Linear Discriminant Analysis, to temporal immunological data resulting from FIV superinfection in domestic cats. We investigated the co-variation among immunological responses, the differences in immune parameters among four groups of five cats each (uninfected, single and dual infected animals, and the "immune profiles" that discriminate among them over the first four weeks following superinfection. Dual infected cats mount an immune response by 24 days post superinfection that is characterized by elevated levels of CD8 and CD25 cells and increased expression of IL4 and IFNgamma, and FAS. This profile discriminates dual infected cats from cats infected with FIV alone, which show high IL-10 and lower numbers of CD8 and CD25 cells.Multivariate statistical analyses demonstrate both the dynamic nature of the immune response to FIV single and dual infection and the development of a unique immunological profile in dual

  17. Immune and biochemical responses in skin differ between bovine hosts genetically susceptible and resistant to the cattle tick Rhipicephalus microplus.

    Science.gov (United States)

    Franzin, Alessandra Mara; Maruyama, Sandra Regina; Garcia, Gustavo Rocha; Oliveira, Rosane Pereira; Ribeiro, José Marcos Chaves; Bishop, Richard; Maia, Antônio Augusto Mendes; Moré, Daniela Dantas; Ferreira, Beatriz Rossetti; Santos, Isabel Kinney Ferreira de Miranda

    2017-01-31

    abundant in larval and in nymphal salivary glands from ticks feeding on susceptible bovines. Compared with tick-susceptible hosts, genes encoding enzymes producing volatile compounds exhibit significantly lower expression in resistant hosts, which may render them less attractive to larvae; resistant hosts expose ticks to an earlier inflammatory response, which in ticks is associated with significantly lower expression of genes encoding salivary proteins that suppress host immunity, inflammation and coagulation.

  18. Effects of juvenile host density and food availability on adult immune response, parasite resistance and virulence in a Daphnia-parasite system.

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    Corine N Schoebel

    Full Text Available Host density can increase infection rates and reduce host fitness as increasing population density enhances the risk of becoming infected either through increased encounter rate or because host condition may decline. Conceivably, potential hosts could take high host density as a cue to up-regulate their defence systems. However, as host density usually covaries with food availability, it is difficult to examine the importance of host density in isolation. Thus, we performed two full-factorial experiments that varied juvenile densities of Daphnia magna (a freshwater crustacean and food availability independently. We also included a simulated high-density treatment, where juvenile experimental animals were kept in filtered media that previously maintained Daphnia at high-density. Upon reaching adulthood, we exposed the Daphnia to their sterilizing bacterial parasite, Pasteuria ramosa, and examined how the juvenile treatments influenced the likelihood and severity of infection (Experiment I and host immune investment (Experiment II. Neither juvenile density nor food treatments affected the likelihood of infection; however, well-fed hosts that were well-fed as juveniles produced more offspring prior to sterilization than their less well-fed counterparts. By contrast, parasite growth was independent of host juvenile resources or host density. Parasite-exposed hosts had a greater number of circulating haemocytes than controls (i.e., there was a cellular immune response, but the magnitude of immune response was not mediated by food availability or host density. These results suggest that density dependent effects on disease arise primarily through correlated changes in food availability: low food could limit parasitism and potentially curtail epidemics by reducing both the host's and parasite's reproduction as both depend on the same food.

  19. Host immune responses to a viral immune modulating protein: immunogenicity of viral interleukin-10 in rhesus cytomegalovirus-infected rhesus macaques.

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    Meghan K Eberhardt

    Full Text Available Considerable evidence has accumulated that multiple viruses, bacteria, and protozoa manipulate interleukin-10 (IL-10-mediated signaling through the IL-10 receptor (IL-10R in ways that could enable establishment of a persistent microbial infection. This suggests that inhibition of pathogen targeting of IL-10/IL-10R signaling could prevent microbial persistence. Human cytomegalovirus (HCMV and rhesus cytomegalovirus (RhCMV express a viral interleukin-10 (cmvIL-10 and rhcmvIL-10, respectively with comparable immune modulating properties in vitro to that of their host's cellular IL-10 (cIL-10. A prior study noted that rhcmvIL-10 alters innate and adaptive immunity to RhCMV in vivo, consistent with a central role for rhcmvIL-10 during acute virus-host interactions. Since cmvIL-10 and rhcmvIL-10 are extremely divergent from the cIL-10 of their respective hosts, vaccine-mediated neutralization of their function could inhibit establishment of viral persistence without inhibition of cIL-10.As a prelude to evaluating cmvIL-10-based vaccines in humans, the rhesus macaque model of HCMV was used to interrogate peripheral and mucosal immune responses to rhcmvIL-10 in RhCMV-infected animals. ELISA were used to detect rhcmvIL-10-binding antibodies in plasma and saliva, and an IL-12-based bioassay was used to quantify plasma antibodies that neutralized rhcmvIL-10 function. rhcmvIL-10 is highly immunogenic during RhCMV infection, stimulating high avidity rhcmvIL-10-binding antibodies in the plasma of all infected animals. Most infected animals also exhibited plasma antibodies that partially neutralized rhcmvIL-10 function but did not cross-neutralize the function of rhesus cIL-10. Notably, minimally detectable rhcmvIL-10-binding antibodies were detected in saliva.This study demonstrates that rhcmvIL-10, as a surrogate for cmvIL-10, is a viable vaccine candidate because (1 it is highly immunogenic during natural RhCMV infection, and (2 neutralizing antibodies to

  20. Adaptive immunity alters distinct host feeding pathways during nematode induced inflammation, a novel mechanism in parasite expulsion.

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    John J Worthington

    2013-01-01

    Full Text Available Gastrointestinal infection is often associated with hypophagia and weight loss; however, the precise mechanisms governing these responses remain poorly defined. Furthermore, the possibility that alterations in feeding during infection may be beneficial to the host requires further study. We used the nematode Trichinella spiralis, which transiently inhabits the small intestine before migrating to skeletal muscle, as a biphasic model of infection to determine the cellular and molecular pathways controlling feeding during enteric and peripheral inflammation. Through the infection of genetically modified mice lacking cholecystokinin, Tumor necrosis factor α receptors and T and B-cells, we observed a biphasic hypophagic response to infection resulting from two separate immune-driven mechanisms. The enteroendocrine I-cell derived hormone cholecystokinin is an essential mediator of initial hypophagia and is induced by CD4+ T-cells during enteritis. In contrast, the second hypophagic response is extra-intestinal and due to the anorectic effects of TNFα during peripheral infection of the muscle. Moreover, via maintaining naive levels of the adipose secreted hormone leptin throughout infection we demonstrate a novel feedback loop in the immunoendocrine axis. Immune driven I-cell hyperplasia and resultant weight loss leads to a reduction in the inflammatory adipokine leptin, which in turn heightens protective immunity during infection. These results characterize specific immune mediated mechanisms which reduce feeding during intestinal or peripheral inflammation. Importantly, the molecular mediators of each phase are entirely separate. The data also introduce the first evidence that I-cell hyperplasia is an adaptively driven immune response that directly impinges on the outcome to infection.

  1. The Immune Responses of the Animal Hosts of West Nile Virus: A Comparison of Insects, Birds, and Mammals

    Directory of Open Access Journals (Sweden)

    Laura R. H. Ahlers

    2018-04-01

    Full Text Available Vector-borne diseases, including arboviruses, pose a serious threat to public health worldwide. Arboviruses of the flavivirus genus, such as Zika virus (ZIKV, dengue virus, yellow fever virus (YFV, and West Nile virus (WNV, are transmitted to humans from insect vectors and can cause serious disease. In 2017, over 2,000 reported cases of WNV virus infection occurred in the United States, with two-thirds of cases classified as neuroinvasive. WNV transmission cycles through two different animal populations: birds and mosquitoes. Mammals, particularly humans and horses, can become infected through mosquito bites and represent dead-end hosts of WNV infection. Because WNV can infect diverse species, research on this arbovirus has investigated the host response in mosquitoes, birds, humans, and horses. With the growing geographical range of the WNV mosquito vector and increased human exposure, improved surveillance and treatment of the infection will enhance public health in areas where WNV is endemic. In this review, we survey the bionomics of mosquito species involved in Nearctic WNV transmission. Subsequently, we describe the known immune response pathways that counter WNV infection in insects, birds, and mammals, as well as the mechanisms known to curb viral infection. Moreover, we discuss the bacterium Wolbachia and its involvement in reducing flavivirus titer in insects. Finally, we highlight the similarities of the known immune pathways and identify potential targets for future studies aimed at improving antiviral therapeutic and vaccination design.

  2. Signal transduction of Helicobacter pylori during interaction with host cell protein receptors of epithelial and immune cells

    Science.gov (United States)

    Pachathundikandi, Suneesh Kumar; Tegtmeyer, Nicole; Backert, Steffen

    2013-01-01

    Helicobacter pylori infections can induce pathologies ranging from chronic gastritis, peptic ulceration to gastric cancer. Bacterial isolates harbor numerous well-known adhesins, vacuolating cytotoxin VacA, protease HtrA, urease, peptidoglycan, and type IV secretion systems (T4SS). It appears that H. pylori targets more than 40 known host protein receptors on epithelial or immune cells. A series of T4SS components such as CagL, CagI, CagY, and CagA can bind to the integrin α5β1 receptor. Other targeted membrane-based receptors include the integrins αvβ3, αvβ5, and β2 (CD18), RPTP-α/β, GP130, E-cadherin, fibronectin, laminin, CD46, CD74, ICAM1/LFA1, T-cell receptor, Toll-like receptors, and receptor tyrosine kinases EGFR, ErbB2, ErbB3, and c-Met. In addition, H. pylori is able to activate the intracellular receptors NOD1, NOD2, and NLRP3 with important roles in innate immunity. Here we review the interplay of various bacterial factors with host protein receptors. The contribution of these interactions to signal transduction and pathogenesis is discussed. PMID:24280762

  3. Cross-Species Virus-Host Protein-Protein Interactions Inhibiting Innate Immunity

    Science.gov (United States)

    2016-07-01

    diseases are a regular occurrence globally (Figure 1). The Zika virus is the latest example gaining widespread attention. Many of the (re-)emerging...for establishing infection and/or modulating pathogenesis (Figures 2 and 3). 3 Figure 2. Schematic of several virus -host protein interactions within...8725 John J. Kingman Road, MS 6201 Fort Belvoir, VA 22060-6201 T E C H N IC A L R E P O R T DTRA-TR-16-79 Cross-species virus -host

  4. The Polysaccharide Capsule of Campylobacter jejuni 81-176 Modulates the Host Immune Response

    Science.gov (United States)

    2012-12-17

    immune response 3 4 Alexander C. Maue1, Krystle L. Mohawk1, David K. Giles*2, Frédéric Poly1, Cheryl 5 P. Ewing1, Yuening Jiao3, Ginyoung Lee3, Zuchao...McGowan, D. Musher , A. Martin and J. 652 Richards. 1998. Phosphorylcholine on the lipooligosaccharide of 653 Haemophilus influnezae contributes to

  5. Pseudomonas syringae evades host immunity by degrading flagellin monomers with alkaline protease AprA

    NARCIS (Netherlands)

    Pel, Michiel J C; van Dijken, Anja J H; Bardoel, Bart W; Seidl, Michael F; van der Ent, Sjoerd; van Strijp, Jos A G; Pieterse, Corné M J

    Bacterial flagellin molecules are strong inducers of innate immune responses in both mammals and plants. The opportunistic pathogen Pseudomonas aeruginosa secretes an alkaline protease called AprA that degrades flagellin monomers. Here, we show that AprA is widespread among a wide variety of

  6. Pseudomonas syringae evades host Immunity by degrading flagellin monomers with alkaline protease AprA

    NARCIS (Netherlands)

    Pel, M.J.C.; Van Dijken, A.J.H.; Bardoel, B.W.; Seidl, M.F; Van der Ent, S.; Van Strijp, J.A.G.

    2014-01-01

    Bacterial flagellin molecules are strong inducers of innate immune responses in both mammals and plants. The opportunistic pathogen Pseudomonas aeruginosa secretes an alkaline protease called AprA that degrades flagellin monomers. Here, we show that AprA is widespread among a wide variety of

  7. Effect of nalbuphine preemptive analgesia combined with ropivacaine local infiltration on postoperative incision pain, stress response and immune function in children

    Directory of Open Access Journals (Sweden)

    Yu Yang

    2017-10-01

    Full Text Available Objective: To study the effect of nalbuphine preemptive analgesia combined with ropivacaine local infiltration on postoperative incision pain, stress response and immune function in children. Methods: Children who received selective laparotomy in Mianyang Central Hospital between August 2015 and August 2017 were selected and randomly divided into control group, nalbuphine group (N group, ropivacaine group (R group and nalbuphine + ropivacaine group (N+R group. The levels of pain and stress-related mediators in serum and the levels of immune cells in peripheral blood were detected before operation and 24 h after operation. Results: 24 h after operation, serum Cor, NE, MDA, SP, PGE2, BK, NPY, TNF-α, IL-6 and IL-10 levels of four groups of children were significantly higher than those before operation while serum SOD and CAT levels as well as peripheral blood CD3+, CD4+ and CD8+T cell levels were significantly lower than those before operation; serum Cor, NE, MDA, SP, PGE2, BK, NPY, TNF-α, IL-6 and IL-10 levels of N group, R group and N+R group were significantly lower than those of control group while serum SOD and CAT levels as well as peripheral blood CD3+, CD4+ and CD8+T cell levels were significantly higher than those of control group; serum Cor, NE, MDA, SP, PGE2, BK, NPY, TNF-α, IL-6 and IL-10 levels of N+R group were significantly lower than those of N group and R group while serum SOD and CAT levels as well as peripheral blood CD3+, CD4+ and CD8+T cell levels were significantly higher than those of N group and R group. Conclusion: Nalbuphine preemptive analgesia combined with ropivacaine local infiltration can reduce the postoperative incision pain and stress response and improve the immune function in children.

  8. Roles of the host oxidative immune response and bacterial antioxidant rubrerythrin during Porphyromonas gingivalis infection.

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    Piotr Mydel

    2006-07-01

    Full Text Available The efficient clearance of microbes by neutrophils requires the concerted action of reactive oxygen species and microbicidal components within leukocyte secretory granules. Rubrerythrin (Rbr is a nonheme iron protein that protects many air-sensitive bacteria against oxidative stress. Using oxidative burst-knockout (NADPH oxidase-null mice and an rbr gene knockout bacterial strain, we investigated the interplay between the phagocytic oxidative burst of the host and the oxidative stress response of the anaerobic periodontal pathogen Porphyromonas gingivalis. Rbr ensured the proliferation of P. gingivalis in mice that possessed a fully functional oxidative burst response, but not in NADPH oxidase-null mice. Furthermore, the in vivo protection afforded by Rbr was not associated with the oxidative burst responses of isolated neutrophils in vitro. Although the phagocyte-derived oxidative burst response was largely ineffective against P. gingivalis infection, the corresponding oxidative response to the Rbr-positive microbe contributed to host-induced pathology via potent mobilization and systemic activation of neutrophils. It appeared that Rbr also provided protection against reactive nitrogen species, thereby ensuring the survival of P. gingivalis in the infected host. The presence of the rbr gene in P. gingivalis also led to greater oral bone loss upon infection. Collectively, these results indicate that the host oxidative burst paradoxically enhances the survival of P. gingivalis by exacerbating local and systemic inflammation, thereby contributing to the morbidity and mortality associated with infection.

  9. Cytokines in the host response to Candida vaginitis: Identifying a role for non-classical immune mediators, S100 alarmins

    Science.gov (United States)

    Yano, Junko; Noverr, Mairi C.; Fidel, Paul L.

    2011-01-01

    Vulvovaginal candidiasis (VVC), caused by Candida albicans, affects a significant number of women during their reproductive years. More than two decades of research have been focused on the mechanisms associated with susceptibility or resistance to symptomatic infection. Adaptive immunity by Th1-type CD4+ T cells and downstream cytokine responses are considered the predominant host defense mechanisms against mucosal Candida infections. However, numerous clinical and animal studies have indicated no or limited protective role of cells and cytokines of the Th1 or Th2 lineage against vaginal infection. The role for Th17 is only now begun to be investigated in-depth for VVC with results already showing significant controversy. On the other hand, a clinical live-challenge study and an established animal model have shown that a symptomatic condition is intimately associated with the vaginal infiltration of polymorphonuclear leukocytes (PMNs) but with no effect on vaginal fungal burden. Subsequent studies identified S100A8 and S100A9 Alarmins as key chemotactic mediators of the acute PMN response. These chemotactic danger signals appear to be secreted by vaginal epithelial cells upon interaction and early adherence of Candida. Thus, instead of a putative immunodeficiency against Candida involving classical immune cells and cytokines of the adaptive response, the pathological inflammation in VVC is now considered a consequence of a non-productive innate response initiated by non-classical immune mediators. PMID:22182685

  10. Salmonella Typhi Colonization Provokes Extensive Transcriptional Changes Aimed at Evading Host Mucosal Immune Defense During Early Infection of Human Intestinal Tissue

    Directory of Open Access Journals (Sweden)

    K.P. Nickerson

    2018-05-01

    Full Text Available Commensal microorganisms influence a variety of host functions in the gut, including immune response, glucose homeostasis, metabolic pathways and oxidative stress, among others. This study describes how Salmonella Typhi, the pathogen responsible for typhoid fever, uses similar strategies to escape immune defense responses and survive within its human host. To elucidate the early mechanisms of typhoid fever, we performed studies using healthy human intestinal tissue samples and “mini-guts,” organoids grown from intestinal tissue taken from biopsy specimens. We analyzed gene expression changes in human intestinal specimens and bacterial cells both separately and after colonization. Our results showed mechanistic strategies that S. Typhi uses to rearrange the cellular machinery of the host cytoskeleton to successfully invade the intestinal epithelium, promote polarized cytokine release and evade immune system activation by downregulating genes involved in antigen sampling and presentation during infection. This work adds novel information regarding S. Typhi infection pathogenesis in humans, by replicating work shown in traditional cell models, and providing new data that can be applied to future vaccine development strategies. Keywords: Typhoid fever, Salmonella, Snapwell™ system, Human tissue, Terminal ileum, Immune system, Innate immunity, Immune evasion, Host-pathogen interaction, Vaccine development, Intestinal organoids, Organoid monolayer

  11. Immunization

    Science.gov (United States)

    ... a lot worse. Some are even life-threatening. Immunization shots, or vaccinations, are essential. They protect against ... B, polio, tetanus, diphtheria, and pertussis (whooping cough). Immunizations are important for adults as well as children. ...

  12. Enhanced immune responses by skin vaccination with influenza subunit vaccine in young hosts.

    Science.gov (United States)

    Koutsonanos, Dimitrios G; Esser, E Stein; McMaster, Sean R; Kalluri, Priya; Lee, Jeong-Woo; Prausnitz, Mark R; Skountzou, Ioanna; Denning, Timothy L; Kohlmeier, Jacob E; Compans, Richard W

    2015-09-08

    Skin has gained substantial attention as a vaccine target organ due to its immunological properties, which include a high density of professional antigen presenting cells (APCs). Previous studies have demonstrated the effectiveness of this vaccination route not only in animal models but also in adults. Young children represent a population group that is at high risk from influenza infection. As a result, this group could benefit significantly from influenza vaccine delivery approaches through the skin and the improved immune response it can induce. In this study, we compared the immune responses in young BALB/c mice upon skin delivery of influenza vaccine with vaccination by the conventional intramuscular route. Young mice that received 5 μg of H1N1 A/Ca/07/09 influenza subunit vaccine using MN demonstrated an improved serum antibody response (IgG1 and IgG2a) when compared to the young IM group, accompanied by higher numbers of influenza-specific antibody secreting cells (ASCs) in the bone marrow. In addition, we observed increased activation of follicular helper T cells and formation of germinal centers in the regional lymph nodes in the MN immunized group, rapid clearance of the virus from their lungs as well as complete survival, compared with partial protection observed in the IM-vaccinated group. Our results support the hypothesis that influenza vaccine delivery through the skin would be beneficial for protecting the high-risk young population from influenza infection. Copyright © 2015. Published by Elsevier Ltd.

  13. Direct fed microbial supplementation repartitions host energy to the immune system.

    Science.gov (United States)

    Qiu, R; Croom, J; Ali, R A; Ballou, A L; Smith, C D; Ashwell, C M; Hassan, H M; Chiang, C-C; Koci, M D

    2012-08-01

    Direct fed microbials and probiotics are used to promote health in livestock and poultry; however, their mechanism of action is still poorly understood. We previously reported that direct fed microbial supplementation in young broilers reduced ileal respiration without changing whole-body energy expenditure. The current studies were conducted to further investigate the effects of a direct fed microbial on energy metabolism in different tissues of broilers. One hundred ninety-two 1-d-old broiler chicks (16 chicks/pen) were randomly assigned to 2 dietary groups: standard control starter diet (CSD) and CSD plus direct fed microbial (DFMD; 0.3%) with 6 pens/treatment. Body weight, feed consumption, whole-body energy expenditure, organ mass, tissue respiration rates, and peripheral blood mononuclear cell (PBMC) ATP concentrations were measured to estimate changes in energy metabolism. No differences in whole body energy expenditure or BW gain were observed; however, decreased ileal O(2) respiration (P energy consumption by PBMC corresponded with an altered immune response, broilers were immunized with sheep red blood cells (SRBC) and assayed for differences in their humoral response. The DFMD-fed broilers had a faster rate of antigen specific IgG production (P direct fed microbial used in this study resulted in energy re-partitioning to the immune system and an increase in antibody production independent of changes in whole body metabolism or growth performance.

  14. Sequestration of host-CD59 as potential immune evasion strategy of Trichomonas vaginalis.

    Science.gov (United States)

    Ibáñez-Escribano, Alexandra; Nogal-Ruiz, Juan José; Pérez-Serrano, Jorge; Gómez-Barrio, Alicia; Escario, J Antonio; Alderete, J F

    2015-09-01

    Trichomonas vaginalis is known to evade complement-mediated lysis. Because the genome of T. vaginalis does not possess DNA sequence with homology to human protectin (CD59), a complement lysis restricting factor, we tested the hypothesis that host CD59 acquisition by T. vaginalis organisms mediates resistance to complement killing. This hypothesis was based on the fact that trichomonads are known to associate with host proteins. No CD59 was detected on the surface of T. vaginalis grown in serum-based medium using as probe anti-CD59 monoclonal antibody (MAb). We, therefore, infected mice intraperitoneally with live T. vaginalis, and trichomonads harvested from ascites were tested for binding of CD59. Immunofluorescence showed that parasites had surface CD59. Furthermore, as mouse erythrocytes (RBCs) possess membrane-associated CD59, and trichomonads use RBCs as a nutrient source, organisms were co-cultured with murine RBCs for one week. Parasites were shown to have detectable surface CD59. Importantly, live T. vaginalis with bound CD59 were compared with batch-grown parasites without surface-associated CD59 for sensitivity to complement in human serum. Trichomonads without surface-bound CD59 had a higher level of killing by complement than did parasites with surface CD59. These data show that host CD59 acquired onto the surface by live T. vaginalis may be an alternative mechanism for complement evasion. We describe a novel strategy by T. vaginalis consistent with host protein procurement by this parasite to evade the lytic action of complement. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Host Immune Selection of Rumen Bacteria through Salivary Secretory IgA

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    Janelle M. Fouhse

    2017-05-01

    Full Text Available The rumen microbiome is integral to efficient production in cattle and shows strong host specificity, yet little is known about what host factors shape rumen microbial composition. Secretory immunoglobulin A (SIgA is produced in large amounts in the saliva, can coat both commensal and pathogenic microbes within the gut, and presents a plausible mechanism of host specificity. However, the role salivary SIgA plays in commensal bacteria selection in ruminants remains elusive. The main objectives of this study were to develop an immuno-affinity benchtop method to isolate SIgA-tagged microbiota and to determine if salivary SIgA preferentially binds selected bacteria. We hypothesized that SIgA-tagged bacteria would differ from total bacteria, thus supporting a potential host-derived mechanism in commensal bacterial selection. Whole rumen (n = 9 and oral secretion samples (n = 10 were incubated with magnetic beads conjugated with anti-secretory IgA antibodies to enrich SIgA-tagged microbiota. Microbial DNA from the oral secretion, whole rumen, SIgA-tagged oral secretion, and SIgA-tagged rumen was isolated for amplicon sequencing of V1–V3 region of 16S rDNA genes. Whole rumen and oral secretion had distinctive (P < 0.05 bacterial compositions indicated by the non-parametric multidimensional scaling plot using Euclidean distance metrics. The SIgA-tagged microbiota from rumen and oral secretion had similar abundance of Bacteroidetes, Actinobacteria, Fibrobacter, candidate phyla TM7, and Tenericutes and are clustered tightly. Composition of SIgA-tagged oral secretion microbiota was more similar to whole rumen microbiota than whole oral secretion due to enrichment of rumen bacteria (Lachnospiraceae and depletion of oral taxa (Streptococcus, Rothia, Neisseriaceae, and Lactobacillales. In conclusion, SIgA-tagged oral secretion microbiota had an increased resemblance to whole rumen microbiota, suggesting salivary SIgA-coating may be one host

  16. Pseudomonas syringae evades host Immunity by degrading flagellin monomers with alkaline protease AprA

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    Pel, M.J.C.; Van Dijken, A.J.H.; Bardoel, B.W.; Seidl, M.F; Van der Ent, S.; Van Strijp, J.A.G.

    2014-01-01

    Bacterial flagellin molecules are strong inducers of innate immune responses in both mammals and plants. The opportunistic pathogen Pseudomonas aeruginosa secretes an alkaline protease called AprA that degrades flagellin monomers. Here, we show that AprA is widespread among a wide variety of bacterial species. In addition, we investigated the role of AprA in virulence of the bacterial plant athogen P. syringae pv. tomato DC3000. The AprA-deficient DC3000 ΔaprA knockout mutant was significantl...

  17. Babesia microti Infection Changes Host Spleen Architecture and Is Cleared by a Th1 Immune Response

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    Vitomir Djokic

    2018-01-01

    Full Text Available Babesia microti is a malaria-like parasite, which infects ∼2000 people annually, such that babesiosis is now a notifiable disease in the United States. Immunocompetent individuals often remain asymptomatic and are tested only after they feel ill. Susceptible C3H/HeJ mice show several human-like disease manifestations and are ideal to study pathogenesis of Babesia species. In this study, we examined parasitemia of B. microti at different time points and assessed its impact on hemoglobin levels in blood, on spleen pathology and overall immune response in C3H/HeJ mice. Peak parasitemia of 42.5% was immediately followed by diminished hemoglobin level. Parasitemia at 21 days of infection was barely detectable by microscopy presented 5.7 × 108 to 5.9 × 109B. microti DNA copies confirming the sensitivity of our qPCR. We hypothesize that qPCR detects DNA released from recently lysed parasites or from extracellular B. microti in blood, which are not easily detected in blood smears and might result in under-diagnosis of babesiosis in patients. Splenectomized patients have been reported to show increased babesiosis severity and result in high morbidity and mortality. These results emphasize the importance of splenic immunity in resolution of B. microti infection. Splenomegaly in infected mice associated with destruction of marginal zone with lysed erythrocytes and released B. microti life forms in our experiments support this premise. At conclusion of the experiment at 21 days post-infection, significant splenic B and T cells depletion and increase in macrophages levels were observed in B. microti infected mice suggesting a role of macrophage in disease resolution. Infected mice also showed significantly higher plasmatic concentration of CD4 Th1 cells secreted cytokines such as IL-2 and IFN-γ while cytokines such as IL-4, IL-5, and IL-13 secreted by Th2 cells increase was not always significant. Thus, Th1 cells-mediated immunity appears to be

  18. Systemic Inflammatory and Th17 Immune Activation among Patients Treated for Lumbar Radiculopathy Exceeds that of Patients Treated for Persistent Postoperative Neuropathic Pain.

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    Shamji, Mohammed F; Guha, Daipayan; Paul, Darcia; Shcharinsky, Alina

    2017-09-01

    The pathophysiology of lumbar radiculopathy includes both mechanical compression and biochemical irritation of apposed neural elements. Inflammatory and immune cytokines have been implicated, induced by systemic exposure of immune-privileged intervertebral disc tissue. Surgical intervention provides improved symptoms and quality of life, but persistent postoperative neuropathic pain (PPNP) afflicts a significant fraction of patients. To compare the inflammatory and immune phenotypes among patients undergoing structural surgery for lumbar radiculopathy and spinal cord stimulation for neuropathic pain. Consecutive patients undergoing surgical intervention for lumbar radiculopathy or neuropathic pain were studied. Demographic data included age, gender, and VAS and neuropathic pain scores. Serum was evaluated for cytokine levels (IL-6, Il-17, TNF-α) and cellular content [white blood cell (WBC)/differential, lymphocyte subtypes]. The primary analysis differentiated molecular and cellular profiles between radiculopathy and neuropathic pain patients. Subgroup analysis within the surgical radiculopathy population compared those patients achieving relief of symptoms and those with PPNP. Heightened IL-6, Il-17, and TNF-α levels were observed for the lumbar radiculopathy group compared with the neuropathic pain group. This was complemented by higher WBC count and a greater fraction of Th17 lymphocytes among radiculopathy patients. In the lumbar discectomy subgroup, pain relief was seen among patients with preoperatively elevated IL-17 levels. Those patients with PPNP refractory to surgical discectomy exhibited normal cytokine levels. Differences in Th17 immune activation are seen among radiculopathy and neuropathic pain patients. These cellular and molecular profiles may be translated into biomarkers to improve patient selection for structural spine surgery. Copyright © 2017 by the Congress of Neurological Surgeons

  19. Host Innate Immunity against Hepatitis E Virus and Viral Evasion Mechanisms.

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    Kang, Sangmin; Myoung, Jinjong

    2017-10-28

    Hepatitis E virus (HEV) infections cause epidemic or sporadic acute hepatitis, which are mostly self-limiting. However, viral infection in immunocompromised patients and pregnant women may result in serious consequences, such as chronic hepatitis and liver damage, mortality of the latter of which reaches up to 20-30%. Type I interferon (IFN)-induced antiviral immunity is known to be the first-line defense against virus infection. Upon HEV infection in the cell, the virus genome is recognized by pathogen recognition receptors, leading to rapid activation of intracellular signaling cascades. Expression of type I IFN triggers induction of a barrage of IFN-stimulated genes, helping the cells cope with viral infection. Interestingly, some of the HEV-encoded genes seem to be involved in disrupting signaling cascades for antiviral immune responses, and thus crippling cytokine/chemokine production. Antagonistic mechanisms of type I IFN responses by HEV have only recently begun to emerge, and in this review, we summarize known HEV evasion strategies and compare them with those of other hepatitis viruses.

  20. Immune recognition of Onchocerca volvulus proteins in the human host and animal models of onchocerciasis.

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    Manchang, T K; Ajonina-Ekoti, I; Ndjonka, D; Eisenbarth, A; Achukwi, M D; Renz, A; Brattig, N W; Liebau, E; Breloer, M

    2015-05-01

    Onchocerca volvulus is a tissue-dwelling, vector-borne nematode parasite of humans and is the causative agent of onchocerciasis or river blindness. Natural infections of BALB/c mice with Litomosoides sigmodontis and of cattle with Onchocerca ochengi were used as models to study the immune responses to O. volvulus-derived recombinant proteins (OvALT-2, OvNLT-1, Ov103 and Ov7). The humoral immune response of O. volvulus-infected humans against OvALT-2, OvNLT-1 and Ov7 revealed pronounced immunoglobulin G (IgG) titres which were, however, significantly lower than against the lysate of O. volvulus adult female worms. Sera derived from patients displaying the hyperreactive form of onchocerciasis showed a uniform trend of higher IgG reactivity both to the single proteins and the O. volvulus lysate. Sera derived from L. sigmodontis-infected mice and from calves exposed to O. ochengi transmission in a hyperendemic area also contained IgM and IgG1 specific for O. volvulus-derived recombinant proteins. These results strongly suggest that L. sigmodontis-specific and O. ochengi-specific immunoglobulins elicited during natural infection of mice and cattle cross-reacted with O. volvulus-derived recombinant antigens. Monitoring O. ochengi-infected calves over a 26-month period, provided a comprehensive kinetic of the humoral response to infection that was strictly correlated with parasite load and occurrence of microfilariae.

  1. Effect of general anesthesia combined with epidural anesthesia on the postoperative immune function, stress state and coagulation function in patients with laparoscopic cholecystectomy

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    Yun-Long Zhao

    2017-05-01

    Full Text Available Objective: To study the effect of general anesthesia combined with epidural anesthesia on the postoperative immune function, stress state and coagulation function in patients with laparoscopic cholecystectomy. Methods: 98 patients undergoing selective laparoscopic cholecystectomy in our hospital between May 2014 and August 2016 were selected and randomly divided into the combined anesthesia group who accepted the general anesthesia combined with epidural anesthesia and the general anesthesia group who accepted the total intravenous anesthesia (n=49, peripheral blood was collected after operation to detect the number of CD3+CD4+CD8-T cells, CD3+CD4-CD8+T cells, CD16+CD56+NK cells and CD3- CD19+B cells, serum was collected to detect the levels of stress-related endocrine hormones norepinephrine (NE, cortisol (Cor, insulin (Ins, C-peptide (C-P, free triiodothyronine (FT3, free thyroxine (FT4 as well as coagulation function indexes rostaglandin I2 (PGI2, thromboxane A2 (TXA2, 6-ketone-prostaglandin F1α (6-K-PGI1α and thromboxane B2 (TXB2. Results: The number of CD3+CD4+CD8-T cells, CD3+CD4-CD8+T cells, CD16+CD56+NK cells and CD3-CD19+B cells in peripheral blood of combined anesthesia group were significantly higher than those of intravenous anesthesia group (P<0.05; serum NE, Cor, Ins, C-P, FT3, FT4, TXA2 and TXB2 levels of combined anesthesia group were significantly lower than those of intravenous anesthesia group (P<0.05 while PGI2 and 6-K-PGI1α levels were significantly higher than those of intravenous anesthesia group (P<0.05. Conclusions: General anesthesia combined with epidural anesthesia can improve the postoperative immune function, stress state and hypercoagulable state in patients with laparoscopic cholecystectomy.

  2. Bacterial genotoxin functions as immune-modulator and promotes host survival

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    Riccardo Guidi

    2016-07-01

    Full Text Available Bacterial genotoxins are effectors that cause DNA damage in target cells. Many aspects of the biology of these toxins have been characterised in vitro, such as structure, cellular internalisation pathways and effects on the target cells. However, little is known about their function in vivo. Salmonella enterica serovar Typhi (S. Typhi is a Gram-negative, intracellular bacterium that causes typhoid fever, a debilitating disease infecting more than 20 million people every year. S. Typhi produce a genotoxin named typhoid toxin (TT, but its role in the contest of host infection is poorly characterized. The major obstacle in addressing this issue is that S. Typhi is exclusively a human pathogen. To overcome this limitation, we have used as model bacterium S. Typhimurium, and engineered it to produce endogenous levels of an active and inactive typhoid toxin, hereby named as TT (or genotoxic and cdtB (or control, respectively. To our surprise, infection with the genotoxin strain strongly suppressed intestinal inflammation, leading to a better survival of the host during the acute phase of infection, suggesting typhoid toxin may exert a protective role. The presence of a functional genotoxin was also associated with an increased frequency of asymptomatic carriers.

  3. Synergistic parasite-pathogen interactions mediated by host immunity can drive the collapse of honeybee colonies.

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    Francesco Nazzi

    Full Text Available The health of the honeybee and, indirectly, global crop production are threatened by several biotic and abiotic factors, which play a poorly defined role in the induction of widespread colony losses. Recent descriptive studies suggest that colony losses are often related to the interaction between pathogens and other stress factors, including parasites. Through an integrated analysis of the population and molecular changes associated with the collapse of honeybee colonies infested by the parasitic mite Varroa destructor, we show that this parasite can de-stabilise the within-host dynamics of Deformed wing virus (DWV, transforming a cryptic and vertically transmitted virus into a rapidly replicating killer, which attains lethal levels late in the season. The de-stabilisation of DWV infection is associated with an immunosuppression syndrome, characterized by a strong down-regulation of the transcription factor NF-κB. The centrality of NF-κB in host responses to a range of environmental challenges suggests that this transcription factor can act as a common currency underlying colony collapse that may be triggered by different causes. Our results offer an integrated account for the multifactorial origin of honeybee losses and a new framework for assessing, and possibly mitigating, the impact of environmental challenges on honeybee health.

  4. Adenovirus entry from the apical surface of polarized epithelia is facilitated by the host innate immune response.

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    Poornima L N Kotha

    2015-03-01

    Full Text Available Prevention of viral-induced respiratory disease begins with an understanding of the factors that increase or decrease susceptibility to viral infection. The primary receptor for most adenoviruses is the coxsackievirus and adenovirus receptor (CAR, a cell-cell adhesion protein normally localized at the basolateral surface of polarized epithelia and involved in neutrophil transepithelial migration. Recently, an alternate isoform of CAR, CAREx8, has been identified at the apical surface of polarized airway epithelia and is implicated in viral infection from the apical surface. We hypothesized that the endogenous role of CAREx8 may be to facilitate host innate immunity. We show that IL-8, a proinflammatory cytokine and a neutrophil chemoattractant, stimulates the protein expression and apical localization of CAREx8 via activation of AKT/S6K and inhibition of GSK3β. Apical CAREx8 tethers infiltrating neutrophils at the apical surface of a polarized epithelium. Moreover, neutrophils present on the apical-epithelial surface enhance adenovirus entry into the epithelium. These findings suggest that adenovirus evolved to co-opt an innate immune response pathway that stimulates the expression of its primary receptor, apical CAREx8, to allow the initial infection the intact epithelium. In addition, CAREx8 is a new target for the development of novel therapeutics for both respiratory inflammatory disease and adenoviral infection.

  5. Tumor Necrosis Factor-α Is Required for Mast Cell-Mediated Host Immunity Against Cutaneous Staphylococcus aureus Infection.

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    Liu, Chao; Ouyang, Wei; Xia, Jingyan; Sun, Xiaoru; Zhao, Liying; Xu, Feng

    2018-05-08

    Mast cells (MCs) play a key role in immune process response to invading pathogens. This study assessed the involvement of MCs in controlling Staphylococcus aureus infection in a cutaneous infection model of MC-deficient (KitW-sh/W-sh) mice. KitW-sh/W-sh mice developed significantly larger skin lesions after the cutaneous S. aureus challenge, when compared to wild-type (WT) mice, while MC dysfunction reduced the inflammation response to S. aureus. The levels of tumor necrosis factor (TNF)-α in skin tissues were significantly decreased in KitW-sh/W-sh mice upon infection. Moreover, the exogenous administration of MCs or recombinant TNF-α effectively restored the immune response against S. aureus in KitW-sh/W-sh mice via the recruitment of neutrophils to the infected site. These results indicate that the effects of MC deficiency are largely attributed to the decrease in production of TNF-α in cutaneous S. aureus infection. In addition, S. aureus-induced MC activation was dependent on the c-kit receptor-activated phosphoinositide 3-kinase (PI3K)/AKT/P65-nuclear factor (NF-κB) pathway, which was confirmed by treatment with Masitinib (a c-kit receptor inhibitor), Wortmannin (a PI3K inhibitor), and pyrrolidine dithiocarbamate (a NF-κB inhibitor), respectively. The present study identifies the critical role of MCs in the host defense against S. aureus infection.

  6. Impact of Enterobius vermicularis infection and mebendazole treatment on intestinal microbiota and host immune response.

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    Chin-An Yang

    2017-09-01

    Full Text Available Previous studies on the association of enterobiasis and chronic inflammatory diseases have revealed contradictory results. The interaction of Enterobius vermicularis infection in particular with gut microbiota and induced immune responses has never been thoroughly examined.In order to answer the question of whether exposure to pinworm and mebendazole can shift the intestinal microbial composition and immune responses, we recruited 109 (30 pinworm-negative, 79 pinworm-infected first and fourth grade primary school children in Taichung, Taiwan, for a gut microbiome study and an intestinal cytokine and SIgA analysis. In the pinworm-infected individuals, fecal samples were collected again at 2 weeks after administration of 100 mg mebendazole. Gut microbiota diversity increased after Enterobius infection, and it peaked after administration of mebendazole. At the phylum level, pinworm infection and mebendazole deworming were associated with a decreased relative abundance of Fusobacteria and an increased proportion of Actinobacteria. At the genus level, the relative abundance of the probiotic Bifidobacterium increased after enterobiasis and mebendazole treatment. The intestinal SIgA level was found to be lower in the pinworm-infected group, and was elevated in half of the mebendazole-treated group. A higher proportion of pre-treatment Salmonella spp. was associated with a non-increase in SIgA after mebendazole deworming treatment.Childhood exposure to pinworm plus mebendazole is associated with increased bacterial diversity, an increased abundance of Actinobacteria including the probiotic Bifidobacterium, and a decreased proportion of Fusobacteria. The gut SIgA level was lower in the pinworm-infected group, and was increased in half of the individuals after mebendazole deworming treatment.

  7. Impact of Enterobius vermicularis infection and mebendazole treatment on intestinal microbiota and host immune response.

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    Yang, Chin-An; Liang, Chao; Lin, Chia-Li; Hsiao, Chiung-Tzu; Peng, Ching-Tien; Lin, Hung-Chih; Chang, Jan-Gowth

    2017-09-01

    Previous studies on the association of enterobiasis and chronic inflammatory diseases have revealed contradictory results. The interaction of Enterobius vermicularis infection in particular with gut microbiota and induced immune responses has never been thoroughly examined. In order to answer the question of whether exposure to pinworm and mebendazole can shift the intestinal microbial composition and immune responses, we recruited 109 (30 pinworm-negative, 79 pinworm-infected) first and fourth grade primary school children in Taichung, Taiwan, for a gut microbiome study and an intestinal cytokine and SIgA analysis. In the pinworm-infected individuals, fecal samples were collected again at 2 weeks after administration of 100 mg mebendazole. Gut microbiota diversity increased after Enterobius infection, and it peaked after administration of mebendazole. At the phylum level, pinworm infection and mebendazole deworming were associated with a decreased relative abundance of Fusobacteria and an increased proportion of Actinobacteria. At the genus level, the relative abundance of the probiotic Bifidobacterium increased after enterobiasis and mebendazole treatment. The intestinal SIgA level was found to be lower in the pinworm-infected group, and was elevated in half of the mebendazole-treated group. A higher proportion of pre-treatment Salmonella spp. was associated with a non-increase in SIgA after mebendazole deworming treatment. Childhood exposure to pinworm plus mebendazole is associated with increased bacterial diversity, an increased abundance of Actinobacteria including the probiotic Bifidobacterium, and a decreased proportion of Fusobacteria. The gut SIgA level was lower in the pinworm-infected group, and was increased in half of the individuals after mebendazole deworming treatment.

  8. A downy mildew effector attenuates salicylic acid-triggered immunity in Arabidopsis by interacting with the host mediator complex.

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    Marie-Cécile Caillaud

    2013-12-01

    Full Text Available Plants are continually exposed to pathogen attack but usually remain healthy because they can activate defences upon perception of microbes. However, pathogens have evolved to overcome plant immunity by delivering effectors into the plant cell to attenuate defence, resulting in disease. Recent studies suggest that some effectors may manipulate host transcription, but the specific mechanisms by which such effectors promote susceptibility remain unclear. We study the oomycete downy mildew pathogen of Arabidopsis, Hyaloperonospora arabidopsidis (Hpa, and show here that the nuclear-localized effector HaRxL44 interacts with Mediator subunit 19a (MED19a, resulting in the degradation of MED19a in a proteasome-dependent manner. The Mediator complex of ∼25 proteins is broadly conserved in eukaryotes and mediates the interaction between transcriptional regulators and RNA polymerase II. We found MED19a to be a positive regulator of immunity against Hpa. Expression profiling experiments reveal transcriptional changes resembling jasmonic acid/ethylene (JA/ET signalling in the presence of HaRxL44, and also 3 d after infection with Hpa. Elevated JA/ET signalling is associated with a decrease in salicylic acid (SA-triggered immunity (SATI in Arabidopsis plants expressing HaRxL44 and in med19a loss-of-function mutants, whereas SATI is elevated in plants overexpressing MED19a. Using a PR1::GUS reporter, we discovered that Hpa suppresses PR1 expression specifically in cells containing haustoria, into which RxLR effectors are delivered, but not in nonhaustoriated adjacent cells, which show high PR1::GUS expression levels. Thus, HaRxL44 interferes with Mediator function by degrading MED19, shifting the balance of defence transcription from SA-responsive defence to JA/ET-signalling, and enhancing susceptibility to biotrophs by attenuating SA-dependent gene expression.

  9. Differences in Acinetobacter baumannii strains and host innate immune response determine morbidity and mortality in experimental pneumonia.

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    Anna de Breij

    Full Text Available Despite many reports documenting its epidemicity, little is known on the interaction of Acinetobacter baumannii with its host. To deepen our insight into this relationship, we studied persistence of and host response to different A. baumannii strains including representatives of the European (EU clones I-III in a mouse pneumonia model. Neutropenic mice were inoculated intratracheally with five A. baumannii strains and an A. junii strain and at several days morbidity, mortality, bacterial counts, airway inflammation, and chemo- and cytokine production in lungs and blood were determined. A. baumannii RUH875 and RUH134 (EU clone I and II, respectively and sporadic strain LUH8326 resulted in high morbidity/mortality, whereas A. baumannii LUH5875 (EU clone III, which is less widespread than clone I and II caused less symptoms. A. baumannii type strain RUH3023(T and A. junii LUH5851 did not cause disease. All strains, except A. baumannii RUH3023(T and A. junii LUH5851, survived and multiplied in the lungs for several days. Morbidity and mortality were associated with the severity of lung pathology and a specific immune response characterized by low levels of anti-inflammatory (IL-10 and specific pro-inflammatory (IL-12p40 and IL-23 cytokines at the first day of infection. Altogether, a striking difference in behaviour among the A. baumannii strains was observed with the clone I and II strains being most virulent, whereas the A. baumannii type strain, which is frequently used in virulence studies appeared harmless.

  10. Ethnicity-dependent influence of innate immune genetic markers on morphine PCA requirements and adverse effects in postoperative pain.

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    Somogyi, Andrew A; Sia, Alex T; Tan, Ene-Choo; Coller, Janet K; Hutchinson, Mark R; Barratt, Daniel T

    2016-11-01

    Although several genetic factors have been associated with postsurgical morphine requirements, those involving the innate immune system and cytokines have not been well investigated. The aim of this study was to investigate the contribution of genetic variability in innate immune signalling pathways to variability in morphine dosage after elective caesarean section under spinal anaesthesia in 133 Indian, 230 Malay, and 598 Han Chinese women previously studied. Twenty single nucleotide polymorphisms in 14 genes involved in glial activation (TLR2, TLR4, MYD88, MD2), inflammatory signalling (IL2, IL6, IL10, IL1B, IL6R, TNFA, TGFB1, CRP, CASP1), and neuronal regulation (BDNF) were newly investigated, in addition to OPRM1, COMT, and ABCB1 genetic variability identified previously. Postsurgical patient-controlled analgesia morphine use (mg/24 hours) was binned into 6 normally distributed groups and scored 0 to 5 to facilitate step-down multiple linear regression analysis of genetic predictors, controlling for ethnicity and nongenetic variables. Ethnicity, OPRM1 rs1799971 (increased), TLR2 rs3804100 (decreased), and an interaction between ethnicity and IL1B rs1143634 (increased), predicted 9.8% of variability in morphine use scores in the entire cohort. In the Indian cohort, 14.5% of the variance in morphine use score was explained by IL1B rs1143634 (increased) and TGFB1 rs1800469 (decreased). In Chinese patients, the incidence of postsurgical pain was significantly higher in variant COMT rs4680 genotypes (P = 0.0007) but not in the Malay or Indian cohorts. Innate immune genetics may contribute to variability in postsurgical opioid requirements in an ethnicity-dependent manner.

  11. Hydrogel elasticity and microarchitecture regulate dental-derived mesenchymal stem cell-host immune system cross-talk.

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    Ansari, Sahar; Chen, Chider; Hasani-Sadrabadi, Mohammad Mahdi; Yu, Bo; Zadeh, Homayoun H; Wu, Benjamin M; Moshaverinia, Alireza

    2017-09-15

    The host immune system (T-lymphocytes and their pro-inflammatory cytokines) has been shown to compromise bone regeneration ability of mesenchymal stem cells (MSCs). We have recently shown that hydrogel, used as an encapsulating biomaterial affects the cross-talk among host immune cells and MSCs. However, the role of hydrogel elasticity and porosity in regulation of cross-talk between dental-derived MSCs and immune cells is unclear. In this study, we demonstrate that the modulus of elasticity and porosity of the scaffold influence T-lymphocyte-dental MSC interplay by regulating the penetration of inflammatory T cells and their cytokines. Moreover, we demonstrated that alginate hydrogels with different elasticity and microporous structure can regulate the viability and determine the fate of the encapsulated MSCs through modulation of NF-kB pathway. Our in vivo data show that alginate hydrogels with smaller pores and higher elasticity could prevent pro-inflammatory cytokine-induced MSC apoptosis by down-regulating the Caspase-3- and 8- associated proapoptotic cascades, leading to higher amounts of ectopic bone regeneration. Additionally, dental-derived MSCs encapsulated in hydrogel with higher elasticity exhibited lower expression levels of NF-kB p65 and Cox-2 in vivo. Taken together, our findings demonstrate that the mechanical characteristics and microarchitecture of the microenvironment encapsulating MSCs, in addition to presence of T-lymphocytes and their pro-inflammatory cytokines, affect the fate of encapsulated dental-derived MSCs. In this study, we demonstrate that alginate hydrogel regulates the viability and the fate of the encapsulated dental-derived MSCs through modulation of NF-kB pathway. Alginate hydrogels with smaller pores and higher elasticity prevent pro-inflammatory cytokine-induced MSC apoptosis by down-regulating the Caspase-3- and 8- associated proapoptotic cascade, leading to higher amounts of ectopic bone regeneration. MSCs encapsulated in

  12. Evaluation of host quality of life and immune function in breast cancer patients treated with combination of adjuvant chemotherapy and oral administration of Lentinula edodes mycelia extract

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    Nagashima Y

    2013-07-01

    Full Text Available Yukiko Nagashima,1 Noriko Maeda,2 Shigeru Yamamoto,2 Shigefumi Yoshino,2 Masaaki Oka21Department of Breast and Thyroid Surgery, Shakaihoken Shimonoseki Kosei Hospital, Shimonoseki City, Yamaguchi, Japan; 2Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Ube City, Yamaguchi, JapanPurpose: Anthracycline-based chemotherapies for breast cancer are well known to have adverse effects and can also negatively affect host immune function. There is therefore a necessity for an adjuvant that maintains the quality of life (QOL and immune function of cancer patients receiving anthracycline-based chemotherapies.Patients and methods: The present study investigated the effectiveness of the concomitant use of Lentinula edodes mycelia extract (LEM, an oral immunomodulator, with FEC75 (5-fluorouracil + epirubicin + cyclophosphamide therapy on host QOL and immune function in breast cancer patients with nodal metastases. Ten breast cancer patients with nodal metastases receiving surgery were enrolled in this study. Treatment with 5-fluorouracil (500 mg/m2, epirubicin (75 mg/m2, and cyclophosphamide (500 mg/m2 was performed every 21 days for two courses, and LEM (1800 mg/day by mouth was administered during the second course.Results: In the first course, hematological toxicity was observed and host QOL and immune function were exacerbated. In the second course, however, the number of white blood cells and lymphocytes did not decrease and host QOL was maintained. Furthermore, the cytotoxic activities of natural killer (NK and lymphokine-activated killer cells and the proportion of activated NK and NK T-cells in lymphocytes were maintained in the second course.Conclusion: It has been suggested that the concomitant use of LEM with FEC75 therapy can maintain host QOL and immune function, and offer important implications for an application of LEM as a useful oral adjuvant to anthracycline-based chemotherapies

  13. Surgical Stress Abrogates Pre-Existing Protective T Cell Mediated Anti-Tumor Immunity Leading to Postoperative Cancer Recurrence.

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    Abhirami A Ananth

    Full Text Available Anti-tumor CD8+ T cells are a key determinant for overall survival in patients following surgical resection for solid malignancies. Using a mouse model of cancer vaccination (adenovirus expressing melanoma tumor-associated antigen (TAA-dopachrome tautomerase (AdDCT and resection resulting in major surgical stress (abdominal nephrectomy, we demonstrate that surgical stress results in a reduction in the number of CD8+ T cell that produce cytokines (IFNγ, TNFα, Granzyme B in response to TAA. This effect is secondary to both reduced proliferation and impaired T cell function following antigen binding. In a prophylactic model, surgical stress completely abrogates tumor protection conferred by vaccination in the immediate postoperative period. In a clinically relevant surgical resection model, vaccinated mice undergoing a positive margin resection with surgical stress had decreased survival compared to mice with positive margin resection alone. Preoperative immunotherapy with IFNα significantly extends survival in surgically stressed mice. Importantly, myeloid derived suppressor cell (MDSC population numbers and functional impairment of TAA-specific CD8+ T cell were altered in surgically stressed mice. Our observations suggest that cancer progression may result from surgery-induced suppression of tumor-specific CD8+ T cells. Preoperative immunotherapies aimed at targeting the prometastatic effects of cancer surgery will reduce recurrence and improve survival in cancer surgery patients.

  14. Genetic dissection of host immune response in pneumonia development and progression.

    Science.gov (United States)

    Smelaya, Tamara V; Belopolskaya, Olesya B; Smirnova, Svetlana V; Kuzovlev, Artem N; Moroz, Viktor V; Golubev, Arkadiy M; Pabalan, Noel A; Salnikova, Lyubov E

    2016-10-11

    The role of host genetic variation in pneumonia development and outcome is poorly understood. We studied common polymorphisms in the genes of proinflammatory cytokines (IL6 rs1800795, IL8 rs4073, IL1B rs16944), anti-inflammatory cytokines (IL10 rs1800896, IL4 rs2243250, IL13 rs20541) and toll-like receptors (TLR2 rs5743708 and rs4696480, TLR4 rs4986791, TLR9 rs352139, rs5743836 and rs187084) in patients with community-acquired pneumonia (CAP) (390 cases, 203 controls) and nosocomial pneumonia (355 cases, 216 controls). Experimental data were included in a series of 11 meta-analyses and eight subset analyses related to pneumonia susceptibility and outcome. TLR2 rs5743708 minor genotype appeared to be associated with CAP/Legionnaires' disease/pneumococcal disease. In CAP patients, the IL6 rs1800795-C allele was associated with severe sepsis/septic shock/severe systemic inflammatory response, while the IL10 rs1800896-A allele protected against the development of these critical conditions. To contribute to deciphering of the above results, we performed an in silico analysis and a qualitative synthesis of literature data addressing basal and stimulated genotype-specific expression level. This data together with database information on transcription factors' affinity changes caused by SNPs in putative promoter regions, the results of linkage disequilibrium analysis along with SNPs functional annotations supported assumptions about the complexity underlying the revealed associations.

  15. Transcriptional responses of Leptospira interrogans to host innate immunity: significant changes in metabolism, oxygen tolerance, and outer membrane.

    Directory of Open Access Journals (Sweden)

    Feng Xue

    Full Text Available BACKGROUND: Leptospira interrogans is the major causative agent of leptospirosis. Phagocytosis plays important roles in the innate immune responses to L. interrogans infection, and L. interrogans can evade the killing of phagocytes. However, little is known about the adaptation of L. interrogans during this process. METHODOLOGY/PRINCIPAL FINDINGS: To better understand the interaction of pathogenic Leptospira and innate immunity, we employed microarray and comparative genomics analyzing the responses of L. interrogans to macrophage-derived cells. During this process, L. interrogans altered expressions of many genes involved in carbohydrate and lipid metabolism, energy production, signal transduction, transcription and translation, oxygen tolerance, and outer membrane proteins. Among them, the catalase gene expression was significantly up-regulated, suggesting it may contribute to resisting the oxidative pressure of the macrophages. The expressions of several major outer membrane protein (OMP genes (e.g., ompL1, lipL32, lipL41, lipL48 and ompL47 were dramatically down-regulated (10-50 folds, consistent with previous observations that the major OMPs are differentially regulated in vivo. The persistent down-regulations of these major OMPs were validated by immunoblotting. Furthermore, to gain initial insight into the gene regulation mechanisms in L. interrogans, we re-defined the transcription factors (TFs in the genome and identified the major OmpR TF gene (LB333 that is concurrently regulated with the major OMP genes, suggesting a potential role of LB333 in OMPs regulation. CONCLUSIONS/SIGNIFICANCE: This is the first report on global responses of pathogenic Leptospira to innate immunity, which revealed that the down-regulation of the major OMPs may be an immune evasion strategy of L. interrogans, and a putative TF may be involved in governing these down-regulations. Alterations of the leptospiral OMPs up interaction with host antigen

  16. Epigenetic regulatory pathways involving microRNAs may modulate the host immune response following major trauma.

    Science.gov (United States)

    Owen, Helen C; Torrance, Hew D T; Jones, Timothy F; Pearse, Rupert M; Hinds, Charles J; Brohi, Karim; O'Dwyer, Michael J

    2015-11-01

    Posttraumatic nosocomial pneumonia is a common complication resulting in significant morbidity. Trauma-induced immunocompromise is associated with an enhanced susceptibility to pneumonia. In this study, we explore the hypothesis that posttranscriptional epigenetic regulation of gene expression may be an important factor in determining this immune phenotype. We describe the pattern of production of microRNAss (miRs) and their association with nosocomial pneumonia following severe trauma. A convenience sample of 30 ventilated polytrauma patients ( 5637) and 16 healthy controls were recruited. Messenger RNA and protein levels of key cytokines were quantified within 2 hours of the injury and at 24 hours. Three miRs per cytokine were then selected based on miRBase target prediction scores and quantified using polymerase chain reaction. Nosocomial pneumonia was defined using the Centers for Disease Control and Prevention definitions. Median Injury Severity Score (ISS) was 29, and 47% of the patients developed nosocomial pneumonia. miR-125a and miR-202 decreased by 34% and 77%, respectively, immediately following injury, whereas their target, IL-10, increased messenger RNA levels 3-fold and protein levels 180-fold. Tumor necrosis factor α (TNF-α) and IL-12 gene expression decreased by 68% and 43%, respectively, following injury, and this was mirrored by a 10-fold increase in miR-181, an miR predicted to target TNF-α transcripts. Lower levels of miR-125a and miR-374b were associated with the later acquisition of hospital-acquired pneumonia. Alteration in the expression of miRs with highly predicted complementarity to IL-10 and TNF-α may be an important mechanism regulating the posttraumatic immunosuppressive phenotype in intensive care unit patients. Retrospective observational study, level III.

  17. Recipient Immune Modulation with Atorvastatin for Acute Graft-versus-Host Disease Prophylaxis after Allogeneic Transplantation.

    Science.gov (United States)

    Kanate, Abraham S; Hari, Parameswaran N; Pasquini, Marcelo C; Visotcky, Alexis; Ahn, Kwang W; Boyd, Jennifer; Guru Murthy, Guru Subramanian; Rizzo, J Douglas; Saber, Wael; Drobyski, William; Michaelis, Laura; Atallah, Ehab; Carlson, Karen S; D'Souza, Anita; Fenske, Timothy S; Cumpston, Aaron; Bunner, Pamela; Craig, Michael; Horowitz, Mary M; Hamadani, Mehdi

    2017-08-01

    Atorvastatin administration to both the donors and recipients of matched related donor (MRD) allogeneic hematopoietic cell transplantation (allo-HCT) as acute graft-versus-host disease (GVHD) prophylaxis has been shown to be safe and effective. However, its efficacy as acute GVHD prophylaxis when given only to allo-HCT recipients is unknown. We conducted a phase II study to evaluate the safety and efficacy of atorvastatin-based acute GVHD prophylaxis given only to the recipients of MRD (n = 30) or matched unrelated donor (MUD) (n = 39) allo-HCT, enrolled in 2 separate cohorts. Atorvastatin (40 mg/day) was administered along with standard GVHD prophylaxis consisting of tacrolimus and methotrexate. All patients were evaluable for acute GVHD. The cumulative incidences of grade II to IV acute GVHD at day +100 in the MRD and MUD cohorts were 9.9% (95% confidence interval [CI], 0 to 20%) and 29.6% (95% CI,15.6% to 43.6%), respectively. The cumulative incidences of grade III and IV acute GVHD at day +100 in the MRD and MUD cohorts were 3.4% (95% CI, 0 to 9.7%) and 18.3% (95% CI, 6.3% to 30.4%), respectively. The corresponding rates of moderate/severe chronic GVHD at 1 year were 28.1% (95% CI, 11% to 45.2%) and 38.9% (95% CI, 20.9% to 57%), respectively. In the MRD cohort, the 1-year nonrelapse mortality, relapse rate, progression-free survival, and overall survival were 6.7% (95% CI, 0 to 15.4%), 43.3% (95% CI, 24.9% to 61.7%), 50% (95% CI, 32.1% to 67.9%), and 66.7% (95% CI, 49.8% to 83.6%), respectively. The respective figures for the MUD cohort were 10.3% (95% CI, 8% to 19.7%), 20.5% (95% CI, 7.9% to 33.1%), 69.2% (95% CI, 54.7% to 83.7%), and 79.5% (95% CI, 66.8% to 92.2%), respectively. No grade 4 toxicities attributable to atorvastatin were seen. In conclusion, the addition of atorvastatin to standard GVHD prophylaxis in only the recipients of MRD and MUD allo-HCT appears to be feasible and safe. The preliminary efficacy seen here warrants confirmation in

  18. 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.

  19. Host Th1/Th2 immune response to Taenia solium cyst antigens in relation to cyst burden of neurocysticercosis.

    Science.gov (United States)

    Tharmalingam, J; Prabhakar, A T; Gangadaran, P; Dorny, P; Vercruysse, J; Geldhof, P; Rajshekhar, V; Alexander, M; Oommen, A

    2016-10-01

    Neurocysticercosis (NCC), Taenia solium larval infection of the brain, is an important cause of acquired seizures in endemic countries, which relate to number, location and degenerating cysts in the brain. Multicyst infections are common in endemic countries although single-cyst infection prevails in India. Single-cyst infections in an endemic country suggest a role for host immunity limiting the infection. This study examined ex vivo CD4(+) T cells and in vitro Th1 and Th2 cytokine responses to T. solium cyst antigens of peripheral blood mononuclear cells of healthy subjects from endemic and nonendemic regions and of single- and multicyst-infected patients for association with cyst burden of NCC. T. solium cyst antigens elicited a Th1 cytokine response in healthy subjects of T. solium-endemic and T. solium-non-endemic regions and those with single-cyst infections and a Th2 cytokine response from subjects with multicyst neurocysticercosis. Multicyst neurocysticercosis subjects also exhibited low levels of effector memory CD4(+) T cells. Th1 cytokine response of T. solium exposure and low infectious loads may aid in limiting cyst number. Th2 cytokines and low effector T cells may enable multiple-cyst infections to establish and persist. © 2016 John Wiley & Sons Ltd.

  20. Immune selection and within-host competition can structure the repertoire of variant surface antigens in Plasmodium falciparum -a mathematical model

    DEFF Research Database (Denmark)

    van Noort, Sander P; Nunes, Marta C; Weedall, Gareth D

    2010-01-01

    BACKGROUND: The evolutionary mechanisms structuring the expression pattern of variant surface antigen (VSA) families that allow pathogens to evade immune responses and establish chronic and repeated infections pose major challenges to theoretical research. In Plasmodium falciparum, the best...... subset of PfEMP1 variants tends to dominate in non-immune patients and in patients with severe malaria, while more diverse subsets relate to uncomplicated infection and higher levels of pre-existing protective immunity. METHODOLOGY/PRINCIPAL FINDINGS: Here, we use the available molecular and serological......-host and diverse blocks that are favoured by immune selection at the population level. CONCLUSIONS/SIGNIFICANCE: The application of a monotonic dominance profile to VSAs encoded by a gene family generates two opposing selective forces and, consequently, two distinct clusters of genes emerge in adaptation to naïve...

  1. [Validation of the modified algorithm for predicting host susceptibility to viruses taking into account susceptibility parameters of primary target cell cultures and natural immunity factors].

    Science.gov (United States)

    Zhukov, V A; Shishkina, L N; Safatov, A S; Sergeev, A A; P'iankov, O V; Petrishchenko, V A; Zaĭtsev, B N; Toporkov, V S; Sergeev, A N; Nesvizhskiĭ, Iu V; Vorob'ev, A A

    2010-01-01

    The paper presents results of testing a modified algorithm for predicting virus ID50 values in a host of interest by extrapolation from a model host taking into account immune neutralizing factors and thermal inactivation of the virus. The method was tested for A/Aichi/2/68 influenza virus in SPF Wistar rats, SPF CD-1 mice and conventional ICR mice. Each species was used as a host of interest while the other two served as model hosts. Primary lung and trachea cells and secretory factors of the rats' airway epithelium were used to measure parameters needed for the purpose of prediction. Predicted ID50 values were not significantly different (p = 0.05) from those experimentally measured in vivo. The study was supported by ISTC/DARPA Agreement 450p.

  2. As-CATH1-6, novel cathelicidins with potent antimicrobial and immunomodulatory properties from Alligator sinensis, play pivotal roles in host antimicrobial immune responses.

    Science.gov (United States)

    Chen, Yan; Cai, Shasha; Qiao, Xue; Wu, Mali; Guo, Zhilai; Wang, Renping; Kuang, Yi-Qun; Yu, Haining; Wang, Yipeng

    2017-08-10

    Crocodilians are regarded as possessing a powerful immune system. However, the composition and action of the crocodilian immune system have remained unclear until now. Cathelicidins, the principal family of host defense peptides, play pivotal roles in vertebrate immune defense against microbial invasions. However, cathelicidins from crocodilians have not been extensively studied to date. In the present study, six novel cathelicidins (As-CATH1-6) were identified and characterized from the endangered Chinese alligator ( Alligator sinensis ). As-CATH1-6 exhibit no sequence similarity with any of the known cathelicidins. Structure analysis indicated that As-CATH1-3 adopt a random coil secondary conformation, whereas As-CATH4-6 were predicted to mainly adopt an amphipathic α-helix conformation. Among them, As-CATH4-6 exhibited potent, broad-spectrum and rapid antimicrobial activity by inducing the disruption of cell membrane integrity. They also exhibited strong ability to prevent the formation of bacterial biofilms and eradicate preformed biofilms. Furthermore, As-CATH4-6 exhibited potent anti-inflammatory activity by inhibiting the lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and pro-inflammatory cytokines in mouse peritoneal macrophages. They directly neutralized LPS toxicity and therefore inhibited the binding of LPS to the TLR4 receptor and the subsequent activation of inflammatory response pathways. In a peritonitis mice model, As-CATH2-6 provided effective protection against bacterial infection through enhanced immune cell recruitment. In the host Chinese alligator, As-CATH1-6 are mainly expressed in immune organs and epithelial tissues. Bacterial infection significantly enhances their expression, which implies an important role in host anti-infective response. Taken together, the diversity and multiple functions of As-CATH1-6 partially reveal the powerful immune system of the Chinese alligator. © 2017 The Author(s). Published by Portland

  3. Postoperative pain

    DEFF Research Database (Denmark)

    Kehlet, H; Dahl, J B

    1993-01-01

    also modify various aspects of the surgical stress response, and nociceptive blockade by regional anesthetic techniques has been demonstrated to improve various parameters of postoperative outcome. It is therefore stressed that effective control of postoperative pain, combined with a high degree......Treatment of postoperative pain has not received sufficient attention by the surgical profession. Recent developments concerned with acute pain physiology and improved techniques for postoperative pain relief should result in more satisfactory treatment of postoperative pain. Such pain relief may...

  4. Bifidobacterium breve UCC2003 surface exopolysaccharide production is a beneficial trait mediating commensal-host interaction through immune modulation and pathogen protection.

    Science.gov (United States)

    Fanning, Saranna; Hall, Lindsay J; van Sinderen, Douwe

    2012-01-01

    Bifidobacteria constitute a substantial proportion of the human gut microbiota. There are currently many bifidobacterial strains with claimed probiotic attributes. The mechanism through which these strains reside within their host and exert benefits to the host is far from fully understood. We have shown in the case of Bifidobacterium breve UCC2003 that a cell surface exopolysaccharide (EPS) plays a role in in vivo persistence. Biosynthesis of two possible EPSs is controlled by a bidirectional gene cluster which guides alternate EPS synthesis by means of a reorienting promoter. The presence of EPS impacts on host immune response: the wild type, EPS-positive B. breve UCC2003 efficiently evades the adaptive B-cell host response, while its isogenic, EPS-deficient equivalent elicits a strong adaptive immune response. Functionally, EPS positive strains were more resilient to presence of acid and bile and were responsible for reduced colonization levels of Citrobacter rodentium, a gut pathogen. In conclusion, we have found that EPS is important in host interactions and pathogen protection, the latter indicative of a probiotic ability for the EPS of B. breve UCC2003.

  5. Genome wide transcriptome profiling of a murine acute melioidosis model reveals new insights into how Burkholderia pseudomallei overcomes host innate immunity

    Directory of Open Access Journals (Sweden)

    Nathan Sheila

    2010-11-01

    Full Text Available Abstract Background At present, very little is known about how Burkholderia pseudomallei (B. pseudomallei interacts with its host to elicit melioidosis symptoms. We established a murine acute-phase melioidosis model and used DNA microarray technology to investigate the global host/pathogen interaction. We compared the transcriptome of infected liver and spleen with uninfected tissues over an infection period of 42 hr to identify genes whose expression is altered in response to an acute infection. Results Viable B. pseudomallei cells were consistently detected in the blood, liver and spleen during the 42 hr course of infection. Microarray analysis of the liver and spleen over this time course demonstrated that genes involved in immune response, stress response, cell cycle regulation, proteasomal degradation, cellular metabolism and signal transduction pathways were differentially regulated. Up regulation of toll-like receptor 2 (TLR2 gene expression suggested that a TLR2-mediated signalling pathway is responsible for recognition and initiation of an inflammatory response to the acute B. pseudomallei infection. Most of the highly elevated inflammatory genes are a cohort of "core host immune response" genes commonly seen in general inflammation infections. Concomitant to this initial inflammatory response, we observed an increase in transcripts associated with cell-death, caspase activation and peptidoglysis that ultimately promote tissue injury in the host. The complement system responsible for restoring host cellular homeostasis and eliminating intracellular bacteria was activated only after 24 hr post-infection. However, at this time point, diverse host nutrient metabolic and cellular pathways including glycolysis, fatty acid metabolism and tricarboxylic acid (TCA cycle were repressed. Conclusions This detailed picture of the host transcriptional response during acute melioidosis highlights a broad range of innate immune mechanisms that are

  6. Atomic evidence that modification of H-bonds established with amino acids critical for host-cell binding induces sterile immunity against malaria

    International Nuclear Information System (INIS)

    Patarroyo, Manuel E.; Cifuentes, Gladys; Pirajan, Camilo; Moreno-Vranich, Armando; Vanegas, Magnolia

    2010-01-01

    Based on the 3D X-ray crystallographic structures of relevant proteins of the malaria parasite involved in invasion to host cells and 3D NMR structures of High Activity Binding Peptides (HABPs) and their respective analogues, it was found that HABPs are rendered into highly immunogenic and sterile immunity inducers in the Aotus experimental model by modifying those amino acids that establish H-bonds with other HABPs or binding to host's cells. This finding adds striking and novel physicochemical principles, at the atomic level, for a logical and rational vaccine development methodology against infectious disease, among them malaria.

  7. Atomic evidence that modification of H-bonds established with amino acids critical for host-cell binding induces sterile immunity against malaria

    Energy Technology Data Exchange (ETDEWEB)

    Patarroyo, Manuel E., E-mail: mepatarr@mail.com [Fundacion Instituto de Inmunologia de Colombia (FIDIC), Bogota (Colombia); Universidad Nacional de Colombia, Bogota (Colombia); Cifuentes, Gladys [Fundacion Instituto de Inmunologia de Colombia (FIDIC), Bogota (Colombia); Universidad del Rosario, Bogota (Colombia); Pirajan, Camilo; Moreno-Vranich, Armando [Fundacion Instituto de Inmunologia de Colombia (FIDIC), Bogota (Colombia); Vanegas, Magnolia [Fundacion Instituto de Inmunologia de Colombia (FIDIC), Bogota (Colombia); Universidad Nacional de Colombia, Bogota (Colombia); Universidad del Rosario, Bogota (Colombia)

    2010-04-09

    Based on the 3D X-ray crystallographic structures of relevant proteins of the malaria parasite involved in invasion to host cells and 3D NMR structures of High Activity Binding Peptides (HABPs) and their respective analogues, it was found that HABPs are rendered into highly immunogenic and sterile immunity inducers in the Aotus experimental model by modifying those amino acids that establish H-bonds with other HABPs or binding to host's cells. This finding adds striking and novel physicochemical principles, at the atomic level, for a logical and rational vaccine development methodology against infectious disease, among them malaria.

  8. Distinct temporal roles for the promyelocytic leukaemia (PML protein in the sequential regulation of intracellular host immunity to HSV-1 infection.

    Directory of Open Access Journals (Sweden)

    Thamir Alandijany

    2018-01-01

    Full Text Available Detection of viral nucleic acids plays a critical role in the induction of intracellular host immune defences. However, the temporal recruitment of immune regulators to infecting viral genomes remains poorly defined due to the technical difficulties associated with low genome copy-number detection. Here we utilize 5-Ethynyl-2'-deoxyuridine (EdU labelling of herpes simplex virus 1 (HSV-1 DNA in combination with click chemistry to examine the sequential recruitment of host immune regulators to infecting viral genomes under low multiplicity of infection conditions. Following viral genome entry into the nucleus, PML-nuclear bodies (PML-NBs rapidly entrapped viral DNA (vDNA leading to a block in viral replication in the absence of the viral PML-NB antagonist ICP0. This pre-existing intrinsic host defence to infection occurred independently of the vDNA pathogen sensor IFI16 (Interferon Gamma Inducible Protein 16 and the induction of interferon stimulated gene (ISG expression, demonstrating that vDNA entry into the nucleus alone is not sufficient to induce a robust innate immune response. Saturation of this pre-existing intrinsic host defence during HSV-1 ICP0-null mutant infection led to the stable recruitment of PML and IFI16 into vDNA complexes associated with ICP4, and led to the induction of ISG expression. This induced innate immune response occurred in a PML-, IFI16-, and Janus-Associated Kinase (JAK-dependent manner and was restricted by phosphonoacetic acid, demonstrating that vDNA polymerase activity is required for the robust induction of ISG expression during HSV-1 infection. Our data identifies dual roles for PML in the sequential regulation of intrinsic and innate immunity to HSV-1 infection that are dependent on viral genome delivery to the nucleus and the onset of vDNA replication, respectively. These intracellular host defences are counteracted by ICP0, which targets PML for degradation from the outset of nuclear infection to promote v

  9. Shifts in Host Mucosal Innate Immune Function Are Associated with Ruminal Microbial Succession in Supplemental Feeding and Grazing Goats at Different Ages

    Directory of Open Access Journals (Sweden)

    Jinzhen Jiao

    2017-08-01

    Full Text Available Gastrointestinal microbiota may play an important role in regulating host mucosal innate immune function. This study was conducted to test the hypothesis that age (non-rumination, transition and rumination and feeding type [Supplemental feeding (S vs. Grazing (G] could alter ruminal microbial diversity and maturation of host mucosal innate immune system in goat kids. MiSeq sequencing was applied to investigate ruminal microbial composition and diversity, and RT-PCR was used to test expression of immune-related genes in ruminal mucosa. Results showed that higher (P < 0.05 relative abundances of Prevotella, Butyrivibrio, Pseudobutyrivibrio, Methanobrevibacter.gottschalkii, Neocallimastix, Anoplodinium–Diplodinium, and Polyplastron, and lower relative abundance of Methanosphaera (P = 0.042 were detected in the rumen of S kids when compared to those in G kids. The expression of genes encoding TLRs, IL1α, IL1β and TICAM2 was down-regulated (P < 0.01, while expression of genes encoding tight junction proteins was up-regulated (P < 0.05 in the ruminal mucosa of S kids when compared to that in G kids. Moreover, irrespective of feeding type, relative abundances of ruminal Prevotella, Fibrobacter, Ruminococcus, Butyrivibrio, Methanobrevibacter, Neocallimastix, and Entodinium increased with age. The expression of most genes encoding TLRs and cytokines increased (P < 0.05 from day 0 to 7, while expression of genes encoding tight junction proteins declined with age (P < 0.05. This study revealed that the composition of each microbial domain changed as animals grew, and these changes might be associated with variations in host mucosal innate immune function. Moreover, supplementing goat kids with concentrate could modulate ruminal microbial composition, enhance barrier function and decrease local inflammation. The findings provide useful information in interpreting microbiota and host interactions, and developing nutritional strategies to improve the

  10. Meta-analysis of the Effects of Insect Vector Saliva on Host Immune Responses and Infection of Vector-Transmitted Pathogens: A Focus on Leishmaniasis

    OpenAIRE

    Ockenfels, Brittany; Michael, Edwin; McDowell, Mary Ann

    2014-01-01

    A meta-analysis of the effects of vector saliva on the immune response and progression of vector-transmitted disease, specifically with regard to pathology, infection level, and host cytokine levels was conducted. Infection in the absence or presence of saliva in naïve mice was compared. In addition, infection in mice pre-exposed to uninfected vector saliva was compared to infection in unexposed mice. To control for differences in vector and pathogen species, mouse strain, and experimental de...

  11. Subcutaneous injection of water-soluble multi-walled carbon nanotubes in tumor-bearing mice boosts the host immune activity

    International Nuclear Information System (INIS)

    Meng Jie; Yang Man; Jia Fumin; Kong Hua; Zhang Weiqi; Xu Haiyan; Wang Chaoying; Xie Sishen; Xing Jianmin

    2010-01-01

    The immunological responses induced by oxidized water-soluble multi-walled carbon nanotubes on a hepatocarcinoma tumor-bearing mice model via a local administration of subcutaneous injection were investigated. Experimental results show that the subcutaneously injected carbon nanotubes induced significant activation of the complement system, promoted inflammatory cytokines' production and stimulated macrophages' phagocytosis and activation. All of these responses increased the general activity of the host immune system and inhibited the progression of tumor growth.

  12. Subcutaneous injection of water-soluble multi-walled carbon nanotubes in tumor-bearing mice boosts the host immune activity

    Science.gov (United States)

    Meng, Jie; Yang, Man; Jia, Fumin; Kong, Hua; Zhang, Weiqi; Wang, Chaoying; Xing, Jianmin; Xie, Sishen; Xu, Haiyan

    2010-04-01

    The immunological responses induced by oxidized water-soluble multi-walled carbon nanotubes on a hepatocarcinoma tumor-bearing mice model via a local administration of subcutaneous injection were investigated. Experimental results show that the subcutaneously injected carbon nanotubes induced significant activation of the complement system, promoted inflammatory cytokines' production and stimulated macrophages' phagocytosis and activation. All of these responses increased the general activity of the host immune system and inhibited the progression of tumor growth.

  13. Subcutaneous injection of water-soluble multi-walled carbon nanotubes in tumor-bearing mice boosts the host immune activity

    Energy Technology Data Exchange (ETDEWEB)

    Jie, Meng; Man, Yang; Fumin, Jia; Hua, Kong; Weiqi, Zhang; Haiyan, Xu [Department of Biomedical Engineering, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005 (China); Chaoying, Wang; Sishen, Xie [Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, 8 Nan San Jie, Zhongguancun, Beijing100080 (China); Xing Jianmin, E-mail: xuhy@pumc.edu.cn [Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, 11 Bei San Huan Dong Lu, Beijing 100029 (China)

    2010-04-09

    The immunological responses induced by oxidized water-soluble multi-walled carbon nanotubes on a hepatocarcinoma tumor-bearing mice model via a local administration of subcutaneous injection were investigated. Experimental results show that the subcutaneously injected carbon nanotubes induced significant activation of the complement system, promoted inflammatory cytokines' production and stimulated macrophages' phagocytosis and activation. All of these responses increased the general activity of the host immune system and inhibited the progression of tumor growth.

  14. Infection dynamic of symbiotic bacteria in the pea aphid Acyrthosiphon pisum gut and host immune response at the early steps in the infection process.

    Directory of Open Access Journals (Sweden)

    François Renoz

    Full Text Available In addition to its obligatory symbiont Buchnera aphidicola, the pea aphid Acyrthosiphon pisum can harbor several facultative bacterial symbionts which can be mutualistic in the context of various ecological interactions. Belonging to a genus where many members have been described as pathogen in invertebrates, Serratia symbiotica is one of the most common facultative partners found in aphids. The recent discovery of strains able to grow outside their host allowed us to simulate environmental acquisition of symbiotic bacteria by aphids. Here, we performed an experiment to characterize the A. pisum response to the ingestion of the free-living S. symbiotica CWBI-2.3T in comparison to the ingestion of the pathogenic Serratia marcescens Db11 at the early steps in the infection process. We found that, while S. marcescens Db11 killed the aphids within a few days, S. symbiotica CWBI-2.3T did not affect host survival and colonized the whole digestive tract within a few days. Gene expression analysis of immune genes suggests that S. symbiotica CWBI-2.3T did not trigger an immune reaction, while S. marcescens Db11 did, and supports the hypothesis of a fine-tuning of the host immune response set-up for fighting pathogens while maintaining mutualistic partners. Our results also suggest that the lysosomal system and the JNK pathway are possibly involved in the regulation of invasive bacteria in aphids and that the activation of the JNK pathway is IMD-independent in the pea aphid.

  15. Infection dynamic of symbiotic bacteria in the pea aphid Acyrthosiphon pisum gut and host immune response at the early steps in the infection process.

    Science.gov (United States)

    Renoz, François; Noël, Christine; Errachid, Abdelmounaim; Foray, Vincent; Hance, Thierry

    2015-01-01

    In addition to its obligatory symbiont Buchnera aphidicola, the pea aphid Acyrthosiphon pisum can harbor several facultative bacterial symbionts which can be mutualistic in the context of various ecological interactions. Belonging to a genus where many members have been described as pathogen in invertebrates, Serratia symbiotica is one of the most common facultative partners found in aphids. The recent discovery of strains able to grow outside their host allowed us to simulate environmental acquisition of symbiotic bacteria by aphids. Here, we performed an experiment to characterize the A. pisum response to the ingestion of the free-living S. symbiotica CWBI-2.3T in comparison to the ingestion of the pathogenic Serratia marcescens Db11 at the early steps in the infection process. We found that, while S. marcescens Db11 killed the aphids within a few days, S. symbiotica CWBI-2.3T did not affect host survival and colonized the whole digestive tract within a few days. Gene expression analysis of immune genes suggests that S. symbiotica CWBI-2.3T did not trigger an immune reaction, while S. marcescens Db11 did, and supports the hypothesis of a fine-tuning of the host immune response set-up for fighting pathogens while maintaining mutualistic partners. Our results also suggest that the lysosomal system and the JNK pathway are possibly involved in the regulation of invasive bacteria in aphids and that the activation of the JNK pathway is IMD-independent in the pea aphid.

  16. Mutations in fetal genes involved in innate immunity and host defense against microbes increase risk of preterm premature rupture of membranes (PPROM).

    Science.gov (United States)

    Modi, Bhavi P; Teves, Maria E; Pearson, Laurel N; Parikh, Hardik I; Haymond-Thornburg, Hannah; Tucker, John L; Chaemsaithong, Piya; Gomez-Lopez, Nardhy; York, Timothy P; Romero, Roberto; Strauss, Jerome F

    2017-11-01

    Twin studies have revealed a significant contribution of the fetal genome to risk of preterm birth. Preterm premature rupture of membranes (PPROM) is the leading identifiable cause of preterm delivery. Infection and inflammation of the fetal membranes is commonly found associated with PPROM. We carried out whole exome sequencing (WES) of genomic DNA from neonates born of African-American mothers whose pregnancies were complicated by PPROM (76) or were normal term pregnancies (N = 43) to identify mutations in 35 candidate genes involved in innate immunity and host defenses against microbes. Targeted genotyping of mutations in the candidates discovered by WES was conducted on an additional 188 PPROM cases and 175 controls. We identified rare heterozygous nonsense and frameshift mutations in several of the candidate genes, including CARD6, CARD8, DEFB1, FUT2, MBL2, NLP10, NLRP12, and NOD2. We discovered that some mutations (CARD6, DEFB1, FUT2, MBL2, NLRP10, NOD2) were present only in PPROM cases. We conclude that rare damaging mutations in innate immunity and host defense genes, the majority being heterozygous, are more frequent in neonates born of pregnancies complicated by PPROM. These findings suggest that the risk of preterm birth in African-Americans may be conferred by mutations in multiple genes encoding proteins involved in dampening the innate immune response or protecting the host against microbial infection and microbial products. © 2017 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

  17. Activated Α7nachr Improves Postoperative Cognitive Dysfunction and Intestinal Injury Induced by Cardiopulmonary Bypass in Rats: Inhibition of the Proinflammatory Response Through the Th17 Immune Response

    Directory of Open Access Journals (Sweden)

    Keyan Chen

    2018-04-01

    Full Text Available Backgrund/Aims: To investigate the effects of activated α7 nicotinic acetylcholine receptor (α7nAChR on postoperative cognitive dysfunction (POCD and intestinal injury induced by cardiopulmonary bypass (CPB and its relationship with the Th17 response in order to provide a theoretical basis for organ protection and targeted drug therapy during the perioperative period. Methods: Sprague-Dawley rat models of CPB were established. Rat intestinal and brain injuries were observed after CPB using hematoxylin and eosin staining. Cell apoptosis was determined using terminal deoxynucleotidyl transferase dUTP nick end labeling. Inflammatory factors and markers of brain injury in rat serum were measured using enzyme-linked immunosorbent assay. The expression levels of Bcl-2, Bax, caspase-3, ZO-1, occludin, AQP4, RORγT, and α7nAchR were examined using western blotting. Transcription factor RORγT expression was determined using real-time fluorescent quantitative polymerase chain reaction. Th17 cells in the peripheral blood and spleen were determined using flow cytometry. α7nAchR knockout rats were established. The Th17 response in the peripheral blood and spleen of α7nAchR knockout rats was further verified using flow cytometry. Results: CPB can induce POCD and intestinal injury in rats. α7nAchR activation markedly reduced intestinal injury, POCD, neuronal apoptosis, proinflammatory factor expression, and number of CD4+IL-17+ cells. α7nAchR knockout significantly increased serum D-lactic acid, FABP2, S-100β, NSE, TNF-α, IL-6, and IL-17 secretion. The number of CD4+IL-17+ cells was also significantly increased. Conclusion: α7nAchR activation markedly ameliorates the intestinal injury and POCD induced by CPB. Inhibition of the Th17 immune response can reduce the proinflammatory response, which could provide a new method for clinical perioperative organ protection and targeted drug therapy.

  18. Mycobacterium tuberculosis controls microRNA-99b (miR-99b) expression in infected murine dendritic cells to modulate host immunity.

    Science.gov (United States)

    Singh, Yogesh; Kaul, Vandana; Mehra, Alka; Chatterjee, Samit; Tousif, Sultan; Dwivedi, Ved Prakash; Suar, Mrutyunjay; Van Kaer, Luc; Bishai, William R; Das, Gobardhan

    2013-02-15

    Mycobacterium tuberculosis resides and replicates within host phagocytes by modulating host microbicidal responses. In addition, it suppresses the production of host protective cytokines to prevent activation of and antigen presentation by M. tuberculosis-infected cells, causing dysregulation of host protective adaptive immune responses. Many cytokines are regulated by microRNAs (miRNAs), a newly discovered class of small noncoding RNAs, which have been implicated in modulating host immune responses in many bacterial and viral diseases. Here, we show that miRNA-99b (miR-99b), an orphan miRNA, plays a key role in the pathogenesis of M. tuberculosis infection. We found that miR-99b expression was highly up-regulated in M. tuberculosis strain H37Rv-infected dendritic cells (DCs) and macrophages. Blockade of miR-99b expression by antagomirs resulted in significantly reduced bacterial growth in DCs. Interestingly, knockdown of miR-99b in DCs significantly up-regulated proinflammatory cytokines such as IL-6, IL-12, and IL-1β. Furthermore, mRNA and membrane-bound protein data indicated that inhibition of miR-99b augments TNF-α and TNFRSF-4 production. Thus, miR-99b targets TNF-α and TNFRSF-4 receptor genes. Treatment of anti-miR-99b-transfected DCs with anti-TNF-α antibody resulted in increased bacterial burden. Thus, our findings unveil a novel host evasion mechanism adopted by M. tuberculosis via miR-99b, which may open up new avenues for designing miRNA-based vaccines and therapies.

  19. Mycobacterium tuberculosis Controls MicroRNA-99b (miR-99b) Expression in Infected Murine Dendritic Cells to Modulate Host Immunity*

    Science.gov (United States)

    Singh, Yogesh; Kaul, Vandana; Mehra, Alka; Chatterjee, Samit; Tousif, Sultan; Dwivedi, Ved Prakash; Suar, Mrutyunjay; Van Kaer, Luc; Bishai, William R.; Das, Gobardhan

    2013-01-01

    Mycobacterium tuberculosis resides and replicates within host phagocytes by modulating host microbicidal responses. In addition, it suppresses the production of host protective cytokines to prevent activation of and antigen presentation by M. tuberculosis-infected cells, causing dysregulation of host protective adaptive immune responses. Many cytokines are regulated by microRNAs (miRNAs), a newly discovered class of small noncoding RNAs, which have been implicated in modulating host immune responses in many bacterial and viral diseases. Here, we show that miRNA-99b (miR-99b), an orphan miRNA, plays a key role in the pathogenesis of M. tuberculosis infection. We found that miR-99b expression was highly up-regulated in M. tuberculosis strain H37Rv-infected dendritic cells (DCs) and macrophages. Blockade of miR-99b expression by antagomirs resulted in significantly reduced bacterial growth in DCs. Interestingly, knockdown of miR-99b in DCs significantly up-regulated proinflammatory cytokines such as IL-6, IL-12, and IL-1β. Furthermore, mRNA and membrane-bound protein data indicated that inhibition of miR-99b augments TNF-α and TNFRSF-4 production. Thus, miR-99b targets TNF-α and TNFRSF-4 receptor genes. Treatment of anti-miR-99b-transfected DCs with anti-TNF-α antibody resulted in increased bacterial burden. Thus, our findings unveil a novel host evasion mechanism adopted by M. tuberculosis via miR-99b, which may open up new avenues for designing miRNA-based vaccines and therapies. PMID:23233675

  20. Immune recognition of salivary proteins from the cattle tick Rhipicephalus microplus differs according to the genotype of the bovine host.

    Science.gov (United States)

    Garcia, Gustavo Rocha; Maruyama, Sandra Regina; Nelson, Kristina T; Ribeiro, José Marcos Chaves; Gardinassi, Luiz Gustavo; Maia, Antonio Augusto Mendes; Ferreira, Beatriz Rossetti; Kooyman, Frans N J; de Miranda Santos, Isabel K F

    2017-03-14

    Males of the cattle tick Rhipicephalus microplus produce salivary immunoglobulin-binding proteins and allotypic variations in IgG are associated with tick loads in bovines. These findings indicate that antibody responses may be essential to control tick infestations. Infestation loads with cattle ticks are heritable: some breeds carry high loads of reproductively successful ticks, in others, few ticks feed and they reproduce inefficiently. Different patterns of humoral immunity against tick salivary proteins may explain these phenotypes. We describe the profiles of humoral responses against tick salivary proteins elicited during repeated artificial infestations of bovines of a tick-resistant (Nelore) and a tick-susceptible (Holstein) breed. We measured serum levels of total IgG1, IgG2 and IgE immunoglobulins and of IgG1 and IgG2 antibodies specific for tick salivary proteins. With liquid chromatography followed by mass spectrometry we identified tick salivary proteins that were differentially recognized by serum antibodies from tick-resistant and tick-susceptible bovines in immunoblots of tick salivary proteins separated by two-dimensional electrophoresis. Baseline levels of total IgG1 and IgG2 were significantly higher in tick-susceptible Holsteins compared with resistant Nelores. Significant increases in levels of total IgG1, but not of IgG2 accompanied successive infestations in both breeds. Resistant Nelores presented with significantly higher levels of salivary-specific antibodies before and at the first challenge with tick larvae; however, by the third challenge, tick-susceptible Holsteins presented with significantly higher levels of IgG1 and IgG2 tick salivary protein-specific antibodies. Importantly, sera from tick-resistant Nelores reacted with 39 tick salivary proteins in immunoblots of salivary proteins separated in two dimensions by electrophoresis versus only 21 spots reacting with sera from tick-susceptible Holsteins. Levels of tick saliva

  1. Expression of Early Immune-Response Genes in Lepidopteran Host are Suppressed by Venom From an Endoparasitoid, Pteromalus puparum

    Science.gov (United States)

    The relationships between parasitoids and their insect hosts have attracted attention at two levels. First, the basic biology of host-parasitoid interactions is of fundamental interest. Second, parasitoids have tremendous potential as biological control agents in sustainable agriculture programs. Pt...

  2. Host immunity in the protective response to nasal immunization with a pneumococcal antigen associated to live and heat-killed Lactobacillus casei.

    Science.gov (United States)

    Vintiñi, Elisa O; Medina, Marcela S

    2011-08-11

    At present, available pneumococcal vaccines have failed to eradicate infections caused by S. pneumoniae. Search for effective vaccine continues and some serotype independent pneumococcal proteins are considered as candidates for the design of new vaccines, especially a mucosal vaccine, since pneumococci enter the body through mucosal surfaces. Selection of the appropriate adjuvant is important for mucosal vaccines, and lactic acid bacteria (LAB) with immunostimulant properties are promissory candidates. In this work, we assessed the adjuvant effect of a probiotic strain, Lactobacillus casei (L. casei), when nasally administered with a pneumococcal antigen (pneumococcal protective protein A: PppA) for the prevention of pneumococcal infection. Adjuvanticity of both live (LcV) and heat-killed (LcM) was evaluated and humoral and cellular antigen-specific immune response was assessed in mucosal and systemic compartments. The potential mechanisms induced by nasal immunization were discussed. Nasal immunization of young mice with PppA+LcV and PppA+LcM induced anti-PppA IgA and IgG antibodies in mucosal and systemic compartments and levels of these specific antibodies remained high even at day 45 after the 3rd Immunization (3rd I). These results were correlated with IL-4 induction by the mixture of antigen plus LcV and LcM. Also, PppA+Lc (V and M) induced stimulation of Th1 and Th17 cells involved in the defence against pneumococci. The protection against pneumococcal respiratory challenge at day 30 after the 3rd I showed that PppA+LcV and PppA+LcM immunizations significantly reduced pathogen counts in nasal lavages while prventing their passage into lung and blood. Survival of mice immunized with the co-application of PppA plus LcV and LcM was significantly higher than in mice immunized with PppA alone and control mice when intraperitoneal challenge was performed. No significant differences between the treatments involving LcV and LcM were found. Live and heat-killed L

  3. Host immunity in the protective response to nasal immunization with a pneumococcal antigen associated to live and heat-killed Lactobacillus casei

    Directory of Open Access Journals (Sweden)

    Vintiñi Elisa O

    2011-08-01

    Full Text Available Abstract Background At present, available pneumococcal vaccines have failed to eradicate infections caused by S. pneumoniae. Search for effective vaccine continues and some serotype independent pneumococcal proteins are considered as candidates for the design of new vaccines, especially a mucosal vaccine, since pneumococci enter the body through mucosal surfaces. Selection of the appropriate adjuvant is important for mucosal vaccines, and lactic acid bacteria (LAB with immunostimulant properties are promissory candidates. In this work, we assessed the adjuvant effect of a probiotic strain, Lactobacillus casei (L. casei, when nasally administered with a pneumococcal antigen (pneumococcal protective protein A: PppA for the prevention of pneumococcal infection. Adjuvanticity of both live (LcV and heat-killed (LcM was evaluated and humoral and cellular antigen-specific immune response was assessed in mucosal and systemic compartments. The potential mechanisms induced by nasal immunization were discussed. Results Nasal immunization of young mice with PppA+LcV and PppA+LcM induced anti-PppA IgA and IgG antibodies in mucosal and systemic compartments and levels of these specific antibodies remained high even at day 45 after the 3rd Immunization (3rd I. These results were correlated with IL-4 induction by the mixture of antigen plus LcV and LcM. Also, PppA+Lc (V and M induced stimulation of Th1 and Th17 cells involved in the defence against pneumococci. The protection against pneumococcal respiratory challenge at day 30 after the 3rd I showed that PppA+LcV and PppA+LcM immunizations significantly reduced pathogen counts in nasal lavages while prventing their passage into lung and blood. Survival of mice immunized with the co-application of PppA plus LcV and LcM was significantly higher than in mice immunized with PppA alone and control mice when intraperitoneal challenge was performed. No significant differences between the treatments involving LcV and

  4. Genetics and Molecular Biology of Epstein-Barr Virus-Encoded BART MicroRNA: A Paradigm for Viral Modulation of Host Immune Response Genes and Genome Stability

    Directory of Open Access Journals (Sweden)

    David H. Dreyfus

    2017-01-01

    Full Text Available Epstein-Barr virus, a ubiquitous human herpesvirus, is associated through epidemiologic evidence with common autoimmune syndromes and cancers. However, specific genetic mechanisms of pathogenesis have been difficult to identify. In this review, the author summarizes evidence that recently discovered noncoding RNAs termed microRNA encoded by Epstein-Barr virus BARF (BamHI A right frame termed BART (BamHI A right transcripts are modulators of human immune response genes and genome stability in infected and bystander cells. BART expression is apparently regulated by complex feedback loops with the host immune response regulatory NF-κB transcription factors. EBV-encoded BZLF-1 (ZEBRA protein could also regulate BART since ZEBRA contains a terminal region similar to ankyrin proteins such as IκBα that regulate host NF-κB. BALF-2 (BamHI A left frame transcript, a viral homologue of the immunoglobulin and T cell receptor gene recombinase RAG-1 (recombination-activating gene-1, may also be coregulated with BART since BALF-2 regulatory sequences are located near the BART locus. Viral-encoded microRNA and viral mRNA transferred to bystander cells through vesicles, defective viral particles, or other mechanisms suggest a new paradigm in which bystander or hit-and-run mechanisms enable the virus to transiently or chronically alter human immune response genes as well as the stability of the human genome.

  5. The Neonatal Window of Opportunity: Setting the Stage for Life-Long Host-Microbial Interaction and Immune Homeostasis.

    Science.gov (United States)

    Torow, Natalia; Hornef, Mathias W

    2017-01-15

    The existence of a neonatal window was first highlighted by epidemiological studies that revealed the particular importance of this early time in life for the susceptibility to immune-mediated diseases in humans. Recently, the first animal studies emerged that present examples of early-life exposure-triggered persisting immune events, allowing a detailed analysis of the factors that define this particular time period. The enteric microbiota and the innate and adaptive immune system represent prime candidates that impact on the pathogenesis of immune-mediated diseases and are known to reach a lasting homeostatic equilibrium following a dynamic priming period after birth. In this review, we outline the postnatal establishment of the microbiota and maturation of the innate and adaptive immune system and discuss examples of early-life exposure-triggered immune-mediated diseases that start to shed light on the critical importance of the early postnatal period for life-long immune homeostasis. Copyright © 2017 by The American Association of Immunologists, Inc.

  6. Disruptions of Host Immunity and Inflammation by Giardia Duodenalis: Potential Consequences for Co-Infections in the Gastro-Intestinal Tract

    Directory of Open Access Journals (Sweden)

    James A. Cotton

    2015-11-01

    Full Text Available Giardia duodenalis (syn. G. intestinalis, or G. lamblia is a leading cause of waterborne diarrheal disease that infects hundreds of millions of people annually. Research on Giardia has greatly expanded within the last few years, and our understanding of the pathophysiology and immunology on this parasite is ever increasing. At peak infection, Giardia trophozoites induce pathophysiological responses that culminate in the development of diarrheal disease. However, human data has suggested that the intestinal mucosa of Giardia-infected individuals is devoid of signs of overt intestinal inflammation, an observation that is reproduced in animal models. Thus, our understanding of host inflammatory responses to the parasite remain incompletely understood and human studies and experimental data have produced conflicting results. It is now also apparent that certain Giardia infections contain mechanisms capable of modulating their host’s immune responses. As the oral route of Giardia infection is shared with many other gastrointestinal (GI pathogens, co-infections may often occur, especially in places with poor sanitation and/or improper treatment of drinking water. Moreover, Giardia infections may modulate host immune responses and have been found to protect against the development of diarrheal disease in developing countries. The following review summarizes our current understanding of the immunomodulatory mechanisms of Giardia infections and their consequences for the host, and highlights areas for future research. Potential implications of these immunomodulatory effects during GI co-infection are also discussed.

  7. Perception of pathogenic or beneficial bacteria and their evasion of host immunity: pattern recognition receptors in the frontline

    Czech Academy of Sciences Publication Activity Database

    Trdá, Lucie; Boutrot, F.; Claverie, J.; Brule, D.; Dorey, S.; Poinssot, B.

    2015-01-01

    Roč. 6, APR 8 (2015) ISSN 1664-462X Institutional support: RVO:61389030 Keywords : plant-microbe interactions * innate immunity * evasion Subject RIV: ED - Physiology Impact factor: 4.495, year: 2015

  8. EGFRvIII mCAR-modified T-cell therapy cures mice with established intracerebral glioma and generates host immunity against tumor-antigen loss.

    Science.gov (United States)

    Sampson, John H; Choi, Bryan D; Sanchez-Perez, Luis; Suryadevara, Carter M; Snyder, David J; Flores, Catherine T; Schmittling, Robert J; Nair, Smita K; Reap, Elizabeth A; Norberg, Pamela K; Herndon, James E; Kuan, Chien-Tsun; Morgan, Richard A; Rosenberg, Steven A; Johnson, Laura A

    2014-02-15

    Chimeric antigen receptor (CAR) transduced T cells represent a promising immune therapy that has been shown to successfully treat cancers in mice and humans. However, CARs targeting antigens expressed in both tumors and normal tissues have led to significant toxicity. Preclinical studies have been limited by the use of xenograft models that do not adequately recapitulate the immune system of a clinically relevant host. A constitutively activated mutant of the naturally occurring epidermal growth factor receptor (EGFRvIII) is antigenically identical in both human and mouse glioma, but is also completely absent from any normal tissues. We developed a third-generation, EGFRvIII-specific murine CAR (mCAR), and performed tests to determine its efficacy in a fully immunocompetent mouse model of malignant glioma. At elevated doses, infusion with EGFRvIII mCAR T cells led to cures in all mice with brain tumors. In addition, antitumor efficacy was found to be dependent on lymphodepletive host conditioning. Selective blockade with EGFRvIII soluble peptide significantly abrogated the activity of EGFRvIII mCAR T cells in vitro and in vivo, and may offer a novel strategy to enhance the safety profile for CAR-based therapy. Finally, mCAR-treated, cured mice were resistant to rechallenge with EGFRvIII(NEG) tumors, suggesting generation of host immunity against additional tumor antigens. All together, these data support that third-generation, EGFRvIII-specific mCARs are effective against gliomas in the brain and highlight the importance of syngeneic, immunocompetent models in the preclinical evaluation of tumor immunotherapies. ©2013 AACR

  9. Mnn10 Maintains Pathogenicity in Candida albicans by Extending α-1,6-Mannose Backbone to Evade Host Dectin-1 Mediated Antifungal Immunity.

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    Shi Qun Zhang

    2016-05-01

    Full Text Available The cell wall is a dynamic structure that is important for the pathogenicity of Candida albicans. Mannan, which is located in the outermost layer of the cell wall, has been shown to contribute to the pathogenesis of C. albicans, however, the molecular mechanism by which this occurs remains unclear. Here we identified a novel α-1,6-mannosyltransferase encoded by MNN10 in C. albicans. We found that Mnn10 is required for cell wall α-1,6-mannose backbone biosynthesis and polysaccharides organization. Deletion of MNN10 resulted in significant attenuation of the pathogenesis of C. albicans in a murine systemic candidiasis model. Inhibition of α-1,6-mannose backbone extension did not, however, impact the invasive ability of C. albicans in vitro. Notably, mnn10 mutant restored the invasive capacity in athymic nude mice, which further supports the notion of an enhanced host antifungal defense related to this backbone change. Mnn10 mutant induced enhanced Th1 and Th17 cell mediated antifungal immunity, and resulted in enhanced recruitment of neutrophils and monocytes for pathogen clearance in vivo. We also demonstrated that MNN10 could unmask the surface β-(1,3-glucan, a crucial pathogen-associated molecular pattern (PAMP of C. albicans recognized by host Dectin-1. Our results demonstrate that mnn10 mutant could stimulate an enhanced Dectin-1 dependent immune response of macrophages in vitro, including the activation of nuclear factor-κB, mitogen-activated protein kinase pathways, and secretion of specific cytokines such as TNF-α, IL-6, IL-1β and IL-12p40. In summary, our study indicated that α-1,6-mannose backbone is critical for the pathogenesis of C. albicans via shielding β-glucan from recognition by host Dectin-1 mediated immune recognition. Moreover, our work suggests that inhibition of α-1,6-mannose extension by Mnn10 may represent a novel modality to reduce the pathogenicity of C. albicans.

  10. Host-pathogen interactions between the human innate immune system and Candida albicans—understanding and modeling defense and evasion strategies

    Science.gov (United States)

    Dühring, Sybille; Germerodt, Sebastian; Skerka, Christine; Zipfel, Peter F.; Dandekar, Thomas; Schuster, Stefan

    2015-01-01

    The diploid, polymorphic yeast Candida albicans is one of the most important human pathogenic fungi. C. albicans can grow, proliferate and coexist as a commensal on or within the human host for a long time. However, alterations in the host environment can render C. albicans virulent. In this review, we describe the immunological cross-talk between C. albicans and the human innate immune system. We give an overview in form of pairs of human defense strategies including immunological mechanisms as well as general stressors such as nutrient limitation, pH, fever etc. and the corresponding fungal response and evasion mechanisms. Furthermore, Computational Systems Biology approaches to model and investigate these complex interactions are highlighted with a special focus on game-theoretical methods and agent-based models. An outlook on interesting questions to be tackled by Systems Biology regarding entangled defense and evasion mechanisms is given. PMID:26175718

  11. A novel Meloidogyne graminicola effector, MgMO237, interacts with multiple host defence-related proteins to manipulate plant basal immunity and promote parasitism.

    Science.gov (United States)

    Chen, Jiansong; Hu, Lili; Sun, Longhua; Lin, Borong; Huang, Kun; Zhuo, Kan; Liao, Jinling

    2018-02-27

    Plant-parasitic nematodes can secrete effector proteins into the host tissue to facilitate their parasitism. In this study, we report a novel effector protein, MgMO237, from Meloidogyne graminicola, which is exclusively expressed within the dorsal oesophageal gland cell and markedly up-regulated in parasitic third-/fourth-stage juveniles of M. graminicola. Transient expression of MgMO237 in protoplasts from rice roots showed that MgMO237 was localized in the cytoplasm and nucleus of the host cells. Rice plants overexpressing MgMO237 showed an increased susceptibility to M. graminicola. In contrast, rice plants expressing RNA interference vectors targeting MgMO237 showed an increased resistance to M. graminicola. In addition, yeast two-hybrid and co-immunoprecipitation assays showed that MgMO237 interacted specifically with three rice endogenous proteins, i.e. 1,3-β-glucan synthase component (OsGSC), cysteine-rich repeat secretory protein 55 (OsCRRSP55) and pathogenesis-related BetvI family protein (OsBetvI), which are all related to host defences. Moreover, MgMO237 can suppress host defence responses, including the expression of host defence-related genes, cell wall callose deposition and the burst of reactive oxygen species. These results demonstrate that the effector MgMO237 probably promotes the parasitism of M. graminicola by interacting with multiple host defence-related proteins and suppressing plant basal immunity in the later parasitic stages of nematodes. © 2018 BSPP AND JOHN WILEY & SONS LTD.

  12. The apolipoprotein L family of programmed cell death and immunity genes rapidly evolved in primates at discrete sites of host-pathogen interactions.

    Science.gov (United States)

    Smith, Eric E; Malik, Harmit S

    2009-05-01

    Apolipoprotein L1 (APOL1) is a human protein that confers immunity to Trypanosoma brucei infections but can be countered by a trypanosome-encoded antagonist SRA. APOL1 belongs to a family of programmed cell death genes whose proteins can initiate host apoptosis or autophagic death. We report here that all six members of the APOL gene family (APOL1-6) present in humans have rapidly evolved in simian primates. APOL6, furthermore, shows evidence of an adaptive sweep during recent human evolution. In each APOL gene tested, we found rapidly evolving codons in or adjacent to the SRA-interacting protein domain (SID), which is the domain of APOL1 that interacts with SRA. In APOL6, we also found a rapidly changing 13-amino-acid cluster in the membrane-addressing domain (MAD), which putatively functions as a pH sensor and regulator of cell death. We predict that APOL genes are antagonized by pathogens by at least two distinct mechanisms: SID antagonists, which include SRA, that interact with the SID of various APOL proteins, and MAD antagonists that interact with the MAD hinge base of APOL6. These antagonists either block or prematurely cause APOL-mediated programmed cell death of host cells to benefit the infecting pathogen. These putative interactions must occur inside host cells, in contrast to secreted APOL1 that trafficks to the trypanosome lysosome. Hence, the dynamic APOL gene family appears to be an important link between programmed cell death of host cells and immunity to pathogens.

  13. Association among genetic predisposition, gut microbiota, and host immune response in the etiopathogenesis of inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    P.J. Basso

    2014-09-01

    Full Text Available Inflammatory bowel disease (IBD, which includes Crohn's disease (CD and ulcerative colitis (UC, is a chronic disorder that affects thousands of people around the world. These diseases are characterized by exacerbated uncontrolled intestinal inflammation that leads to poor quality of life in affected patients. Although the exact cause of IBD still remains unknown, compelling evidence suggests that the interplay among immune deregulation, environmental factors, and genetic polymorphisms contributes to the multifactorial nature of the disease. Therefore, in this review we present classical and novel findings regarding IBD etiopathogenesis. Considering the genetic causes of the diseases, alterations in about 100 genes or allelic variants, most of them in components of the immune system, have been related to IBD susceptibility. Dysbiosis of the intestinal microbiota also plays a role in the initiation or perpetuation of gut inflammation, which develops under altered or impaired immune responses. In this context, unbalanced innate and especially adaptive immunity has been considered one of the major contributing factors to IBD development, with the involvement of the Th1, Th2, and Th17 effector population in addition to impaired regulatory responses in CD or UC. Finally, an understanding of the interplay among pathogenic triggers of IBD will improve knowledge about the immunological mechanisms of gut inflammation, thus providing novel tools for IBD control.

  14. Experimental infection studies demonstrating Atlantic salmon as a host and reservoir of viral hemorrhagic septicemia virus type IVa with insights into pathology and host immunity

    Science.gov (United States)

    Lovy, Jan; Piesik, P.; Hershberger, P.K.; Garver, K.A.

    2013-01-01

    In British Columbia, Canada (BC), aquaculture of finfish in ocean netpens has the potential for pathogen transmission between wild and farmed species due to the sharing of an aquatic environment. Viral hemorrhagic septicemia virus (VHSV) is enzootic in BC and causes serious disease in wild Pacific herring, Clupea pallasii, which often enter and remain in Atlantic salmon, Salmo salar, netpens. Isolation of VHSV from farmed Atlantic salmon has been previously documented, but the effects on the health of farmed salmon and the wild fish sharing the environment are unknown. To determine their susceptibility, Atlantic salmon were exposed to a pool of 9 isolates of VHSV obtained from farmed Atlantic salmon in BC by IP-injection or by waterborne exposure and cohabitation with diseased Pacific herring. Disease intensity was quantified by recording mortality, clinical signs, histopathological changes, cellular sites of viral replication, expression of interferon-related genes, and viral tissue titers. Disease ensued in Atlantic salmon after both VHSV exposure methods. Fish demonstrated gross disease signs including darkening of the dorsal skin, bilateral exophthalmia, light cutaneous hemorrhage, and lethargy. The virus replicated within endothelial cells causing endothelial cell necrosis and extensive hemorrhage in anterior kidney. Infected fish demonstrated a type I interferon response as seen by up-regulation of genes for IFNα, Mx, and ISG15. In a separate trial infected salmon transmitted the virus to sympatric Pacific herring. The results demonstrate that farmed Atlantic salmon can develop clinical VHS and virus can persist in the tissues for at least 10 weeks. Avoiding VHS epizootics in Atlantic salmon farms would limit the potential of VHS in farmed Atlantic salmon, the possibility for further host adaptation in this species, and virus spillback to sympatric wild fishes.

  15. A Cross-Talk Between Microbiota-Derived Short-Chain Fatty Acids and the Host Mucosal Immune System Regulates Intestinal Homeostasis and Inflammatory Bowel Disease.

    Science.gov (United States)

    Gonçalves, Pedro; Araújo, João Ricardo; Di Santo, James P

    2018-02-15

    Gut microbiota has a fundamental role in the energy homeostasis of the host and is essential for proper "education" of the immune system. Intestinal microbial communities are able to ferment dietary fiber releasing short-chain fatty acids (SCFAs). The SCFAs, particularly butyrate (BT), regulate innate and adaptive immune cell generation, trafficing, and function. For example, BT has an anti-inflammatory effect by inhibiting the recruitment and proinflammatory activity of neutrophils, macrophages, dendritic cells, and effector T cells and by increasing the number and activity of regulatory T cells. Gut microbial dysbiosis, ie, a microbial community imbalance, has been suggested to play a role in the development of inflammatory bowel disease (IBD). The relationship between dysbiosis and IBD has been difficult to prove, especially in humans, and is probably complex and dynamic, rather than one of a simple cause and effect relationship. However, IBD patients have dysbiosis with reduced numbers of SCFAs-producing bacteria and reduced BT concentration that is linked to a marked increase in the number of proinflammatory immune cells in the gut mucosa of these patients. Thus, microbial dysbiosis and reduced BT concentration may be a factor in the emergence and severity of IBD. Understanding the relationship between microbial dysbiosis and reduced BT concentration to IBD may lead to novel therapeutic interventions.

  16. Mesenchymal Stem Cells (MSCs) Attenuate Cutaneous Sclerodermatous Graft-Versus-Host Disease (Scl-GVHD) through Inhibition of Immune Cell Infiltration in a Mouse Model.

    Science.gov (United States)

    Lim, Ji-Young; Ryu, Da-Bin; Lee, Sung-Eun; Park, Gyeongsin; Min, Chang-Ki

    2017-09-01

    Human chronic graft-versus-host disease (GVHD) shares clinical characteristics with a murine sclerodermatous GVHD model that is characterized by skin thickening and lung fibrosis. A B10.D2 → BALB/c transplant model of sclerodermatous GVHD was used to address the therapeutic effect of mesenchymal stem cells (MSCs) on the development of chronic GVHD. The clinical and pathological severity of cutaneous sclerodermatous GVHD was significantly attenuated in MSC-treated recipients relative to sclerodermatous GVHD control subjects. After MSC treatment, skin collagen production was significantly reduced, with consistent down-regulation of Tgfb expression. Effects of MSCs on molecular markers implicated in persistent transforming growth factor-β signaling and fibrosis, such as PTEN, phosphorylated Smad-2/3, and matrix metalloproteinase-1, were observed in skin tissue. MSCs neither migrate to the skin nor affect the in vivo expansion of immune effector cells, but they inhibited the infiltration of immune effector cells into skin via down-regulation of CCR4 and CCR8 expression on CD4 + T cells and CCR1 on CD11b + monocyte/macrophages. MSCs diminished expression of chemokines such as CCL1, CCL3, CCL8, CCL17, and CCL22 in skin. MSCs were also dependent on stimulated splenocytes to suppress fibroblast proliferation. Our findings indicate that MSCs attenuate the cutaneous sclerodermatous GVHD by selectively blocking immune cell migration and down-regulating chemokines and chemokine receptors. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Trichomonas vaginalis α-Actinin 2 Modulates Host Immune Responses by Inducing Tolerogenic Dendritic Cells via IL-10 Production from Regulatory T Cells.

    Science.gov (United States)

    Lee, Hye-Yeon; Kim, Juri; Ryu, Jae-Sook; Park, Soon-Jung

    2017-08-01

    Trichomonas vaginalis is a pathogen that triggers severe immune responses in hosts. T. vaginalis α-actinin 2, Tvα-actinin 2, has been used to diagnose trichomoniasis. This study was undertaken to examine the role of Tvα-actinin 2 as an antigenic molecule to induce immune responses from humans. Western blot analysis using anti-Tvα-actinin 2 antibodies indicated its presence in the secreted proteins of T. vaginalis. ELISA was employed to measure cytokine production by vaginal epithelial cells, prostate cells, mouse dendritic cells (DCs), or T cells stimulated with T. vaginalis or Tvα-actinin 2 protein. Both T. vaginalis and rTvα-actinin 2 induced cytokine production from epithelial cell lines, including IL-10. Moreover, CD4+CD25- regulatory T cells (Treg cells) incubated with rTvα-actinin 2-treated DCs produced high levels of IL-10. These data indicate that Tvα-actinin 2 modulates immune responses via IL-10 production by Treg cells.

  18. Effect of Probiotic Bacteria on Microbial Host Defense, Growth, and Immune Function in Human Immunodeficiency Virus Type-1 Infection

    Directory of Open Access Journals (Sweden)

    Stig Bengmark

    2011-12-01

    Full Text Available The hypothesis that probiotic administration protects the gut surface and could delay progression of Human Immunodeficiency Virus type1 (HIV-1 infection to the Acquired Immunodeficiency Syndrome (AIDS was proposed in 1995. Over the last five years, new studies have clarified the significance of HIV-1 infection of the gut associated lymphoid tissue (GALT for subsequent alterations in the microflora and breakdown of the gut mucosal barrier leading to pathogenesis and development of AIDS. Current studies show that loss of gut CD4+ Th17 cells, which differentiate in response to normal microflora, occurs early in HIV-1 disease. Microbial translocation and suppression of the T regulatory (Treg cell response is associated with chronic immune activation and inflammation. Combinations of probiotic bacteria which upregulate Treg activation have shown promise in suppressing pro inflammatory immune response in models of autoimmunity including inflammatory bowel disease and provide a rationale for use of probiotics in HIV-1/AIDS. Disturbance of the microbiota early in HIV-1 infection leads to greater dominance of potential pathogens, reducing levels of bifidobacteria and lactobacillus species and increasing mucosal inflammation. The interaction of chronic or recurrent infections, and immune activation contributes to nutritional deficiencies that have lasting consequences especially in the HIV-1 infected child. While effective anti-retroviral therapy (ART has enhanced survival, wasting is still an independent predictor of survival and a major presenting symptom. Congenital exposure to HIV-1 is a risk factor for growth delay in both infected and non-infected infants. Nutritional intervention after 6 months of age appears to be largely ineffective. A meta analysis of randomized, controlled clinical trials of infant formulae supplemented with Bifidobacterium lactis showed that weight gain was significantly greater in infants who received B. lactis compared to

  19. Population differences in host immune factors may influence survival of Gunnison's prairie dogs (Cynomys Gunnisoni) during plague outbreaks

    Science.gov (United States)

    Busch, Joseph D.; Van Andel, Roger; Cordova, Jennifer; Colman, Rebecca E.; Keim, Paul; Rocke, Tonie E.; Leid, Jeff G.; Van Pelt, William E.; Wagner, David M.

    2011-01-01

    Over the past 40 yr, epizootics of plague (Yersinia pestis) in northern Arizona have reduced populations of the Gunnison’s prairie dog (Cynomys gunnisoni), with the exception of a large population found in the Aubrey Valley (AV). To examine potential mechanisms accounting for their survival, we collected prairie dog serum samples in 2005–2006 from AV and a neighboring population near Seligman (SE), Arizona. We quantified gene expression at 58 diverse immune proteins using a multiplexed enzyme-linked immunosorbent assay panel. We found a subset of proteins important in coagulation and inflammation (tissue factor [TF], calbindin [Cal], and thrombopoietin [TPO]) and T-cell responses (CD40L and CD40) that were present in AV at levels two to eight times greater than SE. These results suggest that AV and SE animals might differ in their ability to mount an immune response.

  20. Invasion of Dendritic Cells, Macrophages and Neutrophils by the Bordetella Adenylate Cyclase Toxin: A Subversive Move to Fool Host Immunity

    Czech Academy of Sciences Publication Activity Database

    Fedele, G.; Schiavoni, O.; Adkins, I.; Klímová, Nela; Šebo, Peter

    2017-01-01

    Roč. 9, č. 10 (2017), s. 1-15, č. článku 293. E-ISSN 2072-6651 R&D Projects: GA MZd(CZ) NV16-28126A; GA ČR(CZ) GA13-14547S; GA MŠk(CZ) LM2015064 Institutional support: RVO:61388971 Keywords : immune response * intracellular pathways * phagocytosis Subject RIV: EA - Cell Biology OBOR OECD: Other biological topics Impact factor: 3.030, year: 2016

  1. Host-adaptation of Francisella tularensis alters the bacterium's surface-carbohydrates to hinder effectors of innate and adaptive immunity.

    Directory of Open Access Journals (Sweden)

    Tiffany M Zarrella

    Full Text Available The gram-negative bacterium Francisella tularensis survives in arthropods, fresh water amoeba, and mammals with both intracellular and extracellular phases and could reasonably be expected to express distinct phenotypes in these environments. The presence of a capsule on this bacterium has been controversial with some groups finding such a structure while other groups report that no capsule could be identified. Previously we reported in vitro culture conditions for this bacterium which, in contrast to typical methods, yielded a bacterial phenotype that mimics that of the bacterium's mammalian, extracellular phase.SDS-PAGE and carbohydrate analysis of differentially-cultivated F. tularensis LVS revealed that bacteria displaying the host-adapted phenotype produce both longer polymers of LPS O-antigen (OAg and additional HMW carbohydrates/glycoproteins that are reduced/absent in non-host-adapted bacteria. Analysis of wildtype and OAg-mutant bacteria indicated that the induced changes in surface carbohydrates involved both OAg and non-OAg species. To assess the impact of these HMW carbohydrates on the access of outer membrane constituents to antibody we used differentially-cultivated bacteria in vitro to immunoprecipitate antibodies directed against outer membrane moieties. We observed that the surface-carbohydrates induced during host-adaptation shield many outer membrane antigens from binding by antibody. Similar assays with normal mouse serum indicate that the induced HMW carbohydrates also impede complement deposition. Using an in vitro macrophage infection assay, we find that the bacterial HMW carbohydrate impedes TLR2-dependent, pro-inflammatory cytokine production by macrophages. Lastly we show that upon host-adaptation, the human-virulent strain, F. tularensis SchuS4 also induces capsule production with the effect of reducing macrophage-activation and accelerating tularemia pathogenesis in mice.F. tularensis undergoes host-adaptation which

  2. Intestinal microbiota as modulators of the immune system and neuroimmune system: impact on the host health and homeostasis.

    Science.gov (United States)

    Maranduba, Carlos Magno da Costa; De Castro, Sandra Bertelli Ribeiro; de Souza, Gustavo Torres; Rossato, Cristiano; da Guia, Francisco Carlos; Valente, Maria Anete Santana; Rettore, João Vitor Paes; Maranduba, Claudinéia Pereira; de Souza, Camila Maurmann; do Carmo, Antônio Márcio Resende; Macedo, Gilson Costa; Silva, Fernando de Sá

    2015-01-01

    Many immune-based intestinal disorders, such as ulcerative colitis and Crohn's disease, as well as other illnesses, may have the intestines as an initial cause or aggravator in the development of diseases, even apparently not correlating directly to the intestine. Diabetes, obesity, multiple sclerosis, depression, and anxiety are examples of other illnesses discussed in the literature. In parallel, importance of the gut microbiota in intestinal homeostasis and immunologic conflict between tolerance towards commensal microorganisms and combat of pathogens is well known. Recent researches show that the immune system, when altered by the gut microbiota, influences the state in which these diseases are presented in the patient directly and indirectly. At the present moment, a considerable number of investigations about this subject have been performed and published. However, due to difficulties on correlating information, several speculations and hypotheses are generated. Thus, the present review aims at bringing together how these interactions work-gut microbiota, immune system, and their influence in the neuroimmune system.

  3. Intestinal Microbiota as Modulators of the Immune System and Neuroimmune System: Impact on the Host Health and Homeostasis

    Directory of Open Access Journals (Sweden)

    Carlos Magno da Costa Maranduba

    2015-01-01

    Full Text Available Many immune-based intestinal disorders, such as ulcerative colitis and Crohn’s disease, as well as other illnesses, may have the intestines as an initial cause or aggravator in the development of diseases, even apparently not correlating directly to the intestine. Diabetes, obesity, multiple sclerosis, depression, and anxiety are examples of other illnesses discussed in the literature. In parallel, importance of the gut microbiota in intestinal homeostasis and immunologic conflict between tolerance towards commensal microorganisms and combat of pathogens is well known. Recent researches show that the immune system, when altered by the gut microbiota, influences the state in which these diseases are presented in the patient directly and indirectly. At the present moment, a considerable number of investigations about this subject have been performed and published. However, due to difficulties on correlating information, several speculations and hypotheses are generated. Thus, the present review aims at bringing together how these interactions work—gut microbiota, immune system, and their influence in the neuroimmune system.

  4. Immunonutrition – the influence of early postoperative glutamine supplementation in enteral/parenteral nutrition on immune response, wound healing and length of hospital stay in multiple trauma patients and patients after extensive surgery

    Directory of Open Access Journals (Sweden)

    Lorenz, Kai J.

    2015-12-01

    Full Text Available Introduction: In the postoperative phase, the prognosis of multiple trauma patients with severe brain injuries as well as of patients with extensive head and neck surgery mainly depends on protein metabolism and the prevention of septic complications. Wound healing problems can also result in markedly longer stays in the intensive care unit and general wards. As a result, the immunostimulation of patients in the postoperative phase is expected to improve their immunological and overall health. Patients and methods: A study involving 15 patients with extensive ENT tumour surgery and 7 multiple-trauma patients investigated the effect of enteral glutamine supplementation on immune induction, wound healing and length of hospital stay. Half of the patients received a glutamine-supplemented diet. The control group received an isocaloric, isonitrogenous diet.Results: In summary, we found that total lymphocyte counts, the percentage of activated CD4+DR+ T helper lymphocytes, the in-vitro response of lymphocytes to mitogens, as well as IL-2 plasma levels normalised faster in patients who received glutamine-supplemented diets than in patients who received isocaloric, isonitrogenous diets and that these parameters were even above normal by the end of the second postoperative week.Summary: We believe that providing critically ill patients with a demand-oriented immunostimulating diet is fully justified as it reduces septic complications, accelerates wound healing, and shortens the length of ICU (intensive care unit and general ward stays.

  5. Immunonutrition - the influence of early postoperative glutamine supplementation in enteral/parenteral nutrition on immune response, wound healing and length of hospital stay in multiple trauma patients and patients after extensive surgery.

    Science.gov (United States)

    Lorenz, Kai J; Schallert, Reiner; Daniel, Volker

    2015-01-01

    In the postoperative phase, the prognosis of multiple trauma patients with severe brain injuries as well as of patients with extensive head and neck surgery mainly depends on protein metabolism and the prevention of septic complications. Wound healing problems can also result in markedly longer stays in the intensive care unit and general wards. As a result, the immunostimulation of patients in the postoperative phase is expected to improve their immunological and overall health. A study involving 15 patients with extensive ENT tumour surgery and 7 multiple-trauma patients investigated the effect of enteral glutamine supplementation on immune induction, wound healing and length of hospital stay. Half of the patients received a glutamine-supplemented diet. The control group received an isocaloric, isonitrogenous diet. In summary, we found that total lymphocyte counts, the percentage of activated CD4+DR+ T helper lymphocytes, the in-vitro response of lymphocytes to mitogens, as well as IL-2 plasma levels normalised faster in patients who received glutamine-supplemented diets than in patients who received isocaloric, isonitrogenous diets and that these parameters were even above normal by the end of the second postoperative week. We believe that providing critically ill patients with a demand-oriented immunostimulating diet is fully justified as it reduces septic complications, accelerates wound healing, and shortens the length of ICU (intensive care unit) and general ward stays.

  6. The Impact of “Omic” and Imaging Technologies on Assessing the Host Immune Response to Biodefence Agents

    Directory of Open Access Journals (Sweden)

    Julia A. Tree

    2014-01-01

    Full Text Available Understanding the interactions between host and pathogen is important for the development and assessment of medical countermeasures to infectious agents, including potential biodefence pathogens such as Bacillus anthracis, Ebola virus, and Francisella tularensis. This review focuses on technological advances which allow this interaction to be studied in much greater detail. Namely, the use of “omic” technologies (next generation sequencing, DNA, and protein microarrays for dissecting the underlying host response to infection at the molecular level; optical imaging techniques (flow cytometry and fluorescence microscopy for assessing cellular responses to infection; and biophotonic imaging for visualising the infectious disease process. All of these technologies hold great promise for important breakthroughs in the rational development of vaccines and therapeutics for biodefence agents.

  7. Timing and severity of immunizing diseases in rabbits is controlled by seasonal matching of host and pathogen dynamics

    OpenAIRE

    Wells, Konstans; Brook, Barry W.; Lacy, Robert C.; Mutze, Greg J.; Peacock, David E.; Sinclair, Ron G.; Schwensow, Nina; Cassey, Phillip; O'Hara, Robert B.; Fordham, Damien A.

    2015-01-01

    Infectious diseases can exert a strong influence on the dynamics of host populations, but it remains unclear why such disease-mediated control only occurs under particular environmental conditions. We used 16 years of detailed field data on invasive European rabbits (Oryctolagus cuniculus) in Australia, linked to individual-based stochastic models and Bayesian approximations, to test whether (i) mortality associated with rabbit haemorrhagic disease (RHD) is driven primarily by seasonal matche...

  8. Effect of L-arginine on the growth of Plasmodium falciparum and immune modulation of host cells.

    Science.gov (United States)

    Awasthi, Vikky; Chauhan, Rubika; Chattopadhyay, Debprasad; Das, Jyoti

    2017-01-01

    Malaria is a life-threatening disease caused by Plasmodium parasites. The life-cycle of Plasmodium species involves several stages both in mosquito and the vertebrate host. In the erythrocytic stage, Plasmodium resides inside the red blood cells (RBCs), where it meets most of its nutritional requirement by degrad- ing host's haemoglobin. L-arginine is required for growth and division of cells. The present study was aimed to demonstrate the effect of supplementation of different concentrations of L-arginine and L-citrulline on the growth of parasite, and effect of the culture supernatant on the host's peripheral blood mononuclear cells (PBMCs). To examine the effect of supplementation of L-arginine and L-citrulline, Plasmodium falciparum (3D7 strain) was cultured in RPMI 1640, L-arginine deficient RPMI 1640, and in different concentrations of L-arginine, and L-citrulline supplemented in arginine deficient RPMI 1640 medium. To have a holistic view of in vivo cell activation, the PBMCs isolated from healthy human host were cultured in the supernatant collected from P. falciparum culture. Growth of the parasite was greatly enhanced in L-arginine supplemented media and was found to be concentration dependent. However, parasite growth was compromised in L-citrulline supplemented and L-arginine deficient media. The supernatant collected from L-arginine supplemented parasite media (sArg) showed increased FOXP3 and interleukin-10 (IL-10) expression as compared to the supernatant collected from L-citrulline supple- mented parasite media (sCit). The in vitro culture results showed, decreased parasite growth, and decreased expression of programmed cell death-1 (PD-1) (a coinhibitory molecule) and IL-10 in the L-citrulline supplemented media as compared to L-arginine supplemented media. Hence, it was concluded that L-citrulline supplementation would be a better alternative than L-arginine to inhibit the parasite growth.

  9. Immunity of an alternative host can be overcome by higher densities of its parasitoids Palmistichus elaeisis and Trichospilus diatraeae.

    Directory of Open Access Journals (Sweden)

    Gilberto Santos Andrade

    Full Text Available Interactions of the parasitoids Palmistichus elaeisis Delvare & LaSalle and Trichospilus diatraeae Cherian & Margabandhu (Hymenoptera: Eulophidae with its alternative host Anticarsia gemmatalis (Hübner (Lepidoptera: Noctuidae affect the success or failure of the mass production of these parasitoids for use in integrated pest management programs. The aim of this study was to evaluate changes in the cellular defense and encapsulation ability of A. gemmatalis pupae against P. elaeisis or T. diatraeae in adult parasitoid densities of 1, 3, 5, 7, 9, 11 or 13 parasitoids/pupae. We evaluated the total quantity of circulating hemocytes and the encapsulation rate versus density. Increasing parasitoid density reduced the total number of hemocytes in the hemolymph and the encapsulation rate by parasitized pupae. Furthermore, densities of P. elaeisis above 5 parasitoids/pupae caused higher reduction in total hemocyte numbers. The encapsulation rate fell with increasing parasitoid density. However, parasitic invasion by both species induced generally similar responses. The reduction in defensive capacity of A. gemmatalis is related to the adjustment of the density of these parasitoids to their development in this host. Thus, the role of the density of P. elaeisis or T. diatraeae by pupa is induced suppression of cellular defense and encapsulation of the host, even without them possesses a co-evolutionary history. Furthermore, these findings can predict the success of P. elaeisis and T. diatraeae in the control of insect pests through the use of immunology as a tool for evaluation of natural enemies.

  10. Transcriptomic analysis of host immune and cell death responses associated with the influenza A virus PB1-F2 protein.

    Directory of Open Access Journals (Sweden)

    Ronan Le Goffic

    2011-08-01

    Full Text Available Airway inflammation plays a major role in the pathogenesis of influenza viruses and can lead to a fatal outcome. One of the challenging objectives in the field of influenza research is the identification of the molecular bases associated to the immunopathological disorders developed during infection. While its precise function in the virus cycle is still unclear, the viral protein PB1-F2 is proposed to exert a deleterious activity within the infected host. Using an engineered recombinant virus unable to express PB1-F2 and its wild-type homolog, we analyzed and compared the pathogenicity and host response developed by the two viruses in a mouse model. We confirmed that the deletion of PB1-F2 renders the virus less virulent. The global transcriptomic analyses of the infected lungs revealed a potent impact of PB1-F2 on the response developed by the host. Thus, after two days post-infection, PB1-F2 invalidation severely decreased the number of genes activated by the host. PB1-F2 expression induced an increase in the number and level of expression of activated genes linked to cell death, inflammatory response and neutrophil chemotaxis. When generating interactive gene networks specific to PB1-F2, we identified IFN-γ as a central regulator of PB1-F2-regulated genes. The enhanced cell death of airway-recruited leukocytes was evidenced using an apoptosis assay, confirming the pro-apoptotic properties of PB1-F2. Using a NF-kB luciferase adenoviral vector, we were able to quantify in vivo the implication of NF-kB in the inflammation mediated by the influenza virus infection; we found that PB1-F2 expression intensifies the NF-kB activity. Finally, we quantified the neutrophil recruitment within the airways, and showed that this type of leukocyte is more abundant during the infection of the wild-type virus. Collectively, these data demonstrate that PB1-F2 strongly influences the early host response during IAV infection and provides new insights into the

  11. Antiviral Efficacy and Host Innate Immunity Associated with SB 9200 Treatment in the Woodchuck Model of Chronic Hepatitis B.

    Directory of Open Access Journals (Sweden)

    Kyle E Korolowicz

    Full Text Available SB 9200, an oral prodrug of the dinucleotide SB 9000, is being developed for the treatment of chronic hepatitis B virus (HBV infection and represents a novel class of antivirals. SB 9200 is thought to activate the viral sensor proteins, retinoic acid-inducible gene 1 (RIG-I and nucleotide-binding oligomerization domain-containing protein 2 (NOD2 resulting in interferon (IFN mediated antiviral immune responses in virus-infected cells. Additionally, the binding of SB 9200 to these sensor proteins could also sterically block the ability of the viral polymerase to access pre-genomic RNA for nucleic acid synthesis. The immune stimulating and direct antiviral properties of SB 9200 were evaluated in woodchucks chronically infected with woodchuck hepatitis virus (WHV by daily, oral dosing at 15 and 30 mg/kg for 12 weeks. Prolonged treatment resulted in 2.2 and 3.7 log10 reductions in serum WHV DNA and in 0.5 and 1.6 log10 declines in serum WHV surface antigen from pretreatment level with the lower or higher dose of SB 9200, respectively. SB 9200 treatment also resulted in lower hepatic levels of WHV nucleic acids and antigen and reduced liver inflammation. Following treatment cessation, recrudescence of viral replication was observed but with dose-dependent delays in viral relapse. The antiviral effects were associated with dose-dependent and long-lasting induction of IFN-α, IFN-β and IFN-stimulated genes in blood and liver, which correlated with the prolonged activation of the RIG-I/NOD2 pathway and hepatic presence of elevated RIG-I protein levels. These results suggest that in addition to a direct antiviral activity, SB 9200 induces antiviral immunity during chronic hepadnaviral infection via activation of the viral sensor pathway.

  12. Postoperative radiology

    International Nuclear Information System (INIS)

    Burhenne, H.J.

    1989-01-01

    This paper reports on the importance of postoperative radiology. Most surgical procedures on the alimentary tract are successful, but postoperative complications remain a common occurrence. The radiologist must be familiar with a large variety of possible surgical complications, because it is this specialty that is most commonly called on to render a definitive diagnosis. The decision for reoperation, for instance, is usually based on results from radiologic imaging techniques. These now include ultrasonography, CT scanning, needle biopsy, and interventional techniques in addition to contrast studies and nuclear medicine investigation

  13. Do the Microbiota Influence Vaccines and Protective Immunity to Pathogens? Issues of Sovereignty, Federalism, and Points-Testing in the Prokaryotic and Eukaryotic Spaces of the Host-Microbial Superorganism.

    Science.gov (United States)

    Macpherson, Andrew J

    2018-02-01

    In contrast to live attenuated vaccines, which are designed to induce immunity through a time-limited bloom in systemic tissues, the microbiota is a persistent feature of body surfaces, especially the intestine. The immune responses to the microbiota are idiosyncratic depending on the niche intimacy of different taxa and generally adapt the host to avoid overgrowth and maintain mutualism rather than to eliminate the organisms of that taxon. Both the microbiota and the host have so much molecular cross talk controlling each other, that the prokaryotic and the eukaryotic spaces of the host-microbial superorganism are federal rather than sovereign. This molecular cross talk is vital for the immune system to develop its mature form. Nevertheless, the microbiota/host biomass spaces are rather well separated: The microbiota also limits colonization and penetration of pathogens through intense metabolic competition. Immune responses to those members of the microbiota mutually adapted to intimate association at mucosal surfaces have attractive potential durability, but for clinical use as persistent vehicles they would require personalization and engineered reversibility to manage the immune context and complications in individual human subjects. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

  14. Alternate adenovirus type-pairs for a possible circumvention of host immune response to recombinant adenovirus vectors.

    Science.gov (United States)

    Nász, I; Adám, E; Lengyel, A

    2001-01-01

    With the help of monoclonal antibodies the existence of at least 18 different earlier not known intertype (IT) specific epitopes were demonstrated in different numbers and combinations on the hexons of different adenovirus serotypes. The IT specific epitopes play an important role in the experimental gene therapy and in the recombinant adenovirus vaccination because of the harmful immune response of the recipient organisms directed against the many different epitopes of the adenovirus vector. For the elimination of harmful effect the authors suggest the use of multiple vectors, each prepared from different adenovirus serotypes showing the loosest antigenic relationship to each other. The vectors would be used sequentially when second or multiple administration is needed. For this purpose the authors determined and described 31 such adenovirus type-pairs, which are probably the best alternates for sequential use in experimental gene therapy.

  15. Aedes aegypti Molecular Responses to Zika Virus: Modulation of Infection by the Toll and Jak/Stat Immune Pathways and Virus Host Factors

    Directory of Open Access Journals (Sweden)

    Yesseinia I. Angleró-Rodríguez

    2017-10-01

    Full Text Available Zika (ZIKV and dengue virus (DENV are transmitted to humans by Aedes mosquitoes. However, the molecular interactions between the vector and ZIKV remain largely unexplored. In this work, we further investigated the tropism of ZIKV in two different Aedes aegypti strains and show that the virus infection kinetics, tissue migration, and susceptibility to infection differ between mosquito strains. We also compare the vector transcriptome changes upon ZIKV or DENV infection demonstrating that 40% of the mosquito’s midgut infection-responsive transcriptome is virus-specific at 7 days after virus ingestion. Regulated genes included key factors of the mosquito’s anti-viral immunity. Comparison of the ZIKV and DENV infection-responsive transcriptome data to those available for yellow fever virus and West Nile virus identified 26 genes likely to play key roles in virus infection of Aedes mosquitoes. Through reverse genetic analyses, we show that the Toll and the Jak/Stat innate immune pathways mediate increased resistance to ZIKV infection, and the conserved DENV host factors vATPase and inosine-5′-monophosphate dehydrogenase are also utilized for ZIKV infection.

  16. Host transcriptomic responses to pneumonic plague reveal that Yersinia pestis inhibits both the initial adaptive and innate immune responses in mice.

    Science.gov (United States)

    Yang, Huiying; Wang, Tong; Tian, Guang; Zhang, Qingwen; Wu, Xiaohong; Xin, Youqian; Yan, Yanfeng; Tan, Yafang; Cao, Shiyang; Liu, Wanbing; Cui, Yujun; Yang, Ruifu; Du, Zongmin

    2017-01-01

    Pneumonic plague is the most deadly form of infection caused by Yersinia pestis and can progress extremely fast. However, our understanding on the host transcriptomic response to pneumonic plague is insufficient. Here, we used RNA-sequencing technology to analyze transcriptomic responses in mice infected with fully virulent strain 201 or EV76, a live attenuated vaccine strain lacking the pigmentation locus. Approximately 600 differentially expressed genes (DEGs) were detected in lungs from both 201- and EV76-infected mice at 12h post-infection (hpi). DEGs in lungs of 201-infected mice exceeded 2000 at 48hpi, accompanied by sustained large numbers of DEGs in the liver and spleen; however, limited numbers of DEGs were detected in those organs of EV-infected mice. Remarkably, DEGs in lungs were significantly enriched in critical immune responses pathways in EV76-infected but not 201-infected mice, including antigen processing and presentation, T cell receptor signaling among others. Pathological and bacterial load analyses confirmed the rapid systemic dissemination of 201-infection and the confined EV76-infection in lungs. Our results suggest that fully virulent Y. pestis inhibits both the innate and adaptive immune responses that are substantially stimulated in a self-limited infection, which update our holistic views on the transcriptomic response to pneumonic plague. Copyright © 2016 Elsevier GmbH. All rights reserved.

  17. Comparative Analysis of the Complete Genome of Lactobacillus plantarum GB-LP2 and Potential Candidate Genes for Host Immune System Enhancement.

    Science.gov (United States)

    Kwak, Woori; Kim, Kwondo; Lee, Chul; Lee, Chanho; Kang, Jungsun; Cho, Kyungjin; Yoon, Sook Hee; Kang, Dae-Kyung; Kim, Heebal; Heo, Jaeyoung; Cho, Seoae

    2016-04-28

    Acute respiratory virus infectious diseases are a growing health problem, particularly among children and the elderly. Much effort has been made to develop probiotics that prevent influenza virus infections by enhancing innate immunity in the respiratory tract until vaccines are available. Lactobacillus plantarum GB-LP2, isolated from a traditional Korean fermented vegetable, has exhibited preventive effects on influenza virus infection in mice. To identify the molecular basis of this strain, we conducted a whole-genome assembly study. The single circular DNA chromosome of 3,284,304 bp was completely assembled and 3,250 proteinencoding genes were predicted. Evolutionarily accelerated genes related to the phenotypic trait of anti-infective activities for influenza virus were identified. These genes encode three integral membrane proteins, a teichoic acid export ATP-binding protein and a glucosamine - fructose-6-phosphate aminotransferase involved in host innate immunity, the nonspecific DNA-binding protein Dps, which protects bacteria from oxidative damage, and the response regulator of the three-component quorum-sensing regulatory system, which is related to the capacity of adhesion to the surface of the respiratory tract and competition with pathogens. This is the first study to identify the genetic backgrounds of the antiviral activity in L. plantarum strains. These findings provide insight into the anti-infective activities of L. plantarum and the development of preventive probiotics.

  18. Surgical Stress Response and Postoperative Immune Function After Laparoscopy or Open Surgery With Fast Track or Standard Perioperative Care A Randomized Trial

    NARCIS (Netherlands)

    Veenhof, A. A. F. A.; Vlug, M. S.; van der Pas, M. H. G. M.; Sietses, C.; van der Peet, D. L.; de Lange-de Klerk, E. S. M.; Bonjer, H. J.; Bemelman, W. A.; Cuesta, M. A.

    2012-01-01

    Objective: To evaluate the effect of laparoscopic or open colectomy with fast track or standard perioperative care on patient's immune status and stress response after surgery. Methods: Patients with nonmetastasized colon cancer were randomized to laparoscopic or open colectomy with fast track or

  19. Influence of ESAT-6 secretion system 1 (RD1) of Mycobacterium tuberculosis on the interaction between mycobacteria and the host immune system.

    Science.gov (United States)

    Majlessi, Laleh; Brodin, Priscille; Brosch, Roland; Rojas, Marie-Jésus; Khun, Huot; Huerre, Michel; Cole, Stewart T; Leclerc, Claude

    2005-03-15

    The chromosomal locus encoding the early secreted antigenic target, 6 kDa (ESAT-6) secretion system 1 of Mycobacterium tuberculosis, also referred to as "region of difference 1 (RD1)," is absent from Mycobacterium bovis bacillus Calmette-Guerin (BCG). In this study, using low-dose aerosol infection in mice, we demonstrate that BCG complemented with RD1 (BCG::RD1) displays markedly increased virulence which albeit does not attain that of M. tuberculosis H37Rv. Nevertheless, phenotypic and functional analyses of immune cells at the site of infection show that the capacity of BCG::RD1 to initiate recruitment/activation of immune cells is comparable to that of fully virulent H37Rv. Indeed, in contrast to the parental BCG, BCG::RD1 mimics H37Rv and induces substantial influx of activated (CD44highCD45RB(-)CD62L(-)) or effector (CD45RB(-)CD27(-)) T cells and of activated CD11c(+)CD11bhigh cells to the lungs of aerosol-infected mice. For the first time, using in vivo analysis of transcriptome of inflammatory cytokines and chemokines of lung interstitial CD11c+ cells, we show that in a low-dose aerosol infection model, BCG::RD1 triggered an activation/inflammation program comparable to that induced by H37Rv while parental BCG, due to its overattenuation, did not initiate the activation program in lung interstitial CD11c+ cells. Thus, products encoded by the ESAT-6 secretion system 1 of M. tuberculosis profoundly modify the interaction between mycobacteria and the host innate and adaptive immune system. These modifications can explain the previously described improved protective capacity of BCG::RD1 vaccine candidate against M. tuberculosis challenge.

  20. Foot-and-mouth disease virus 5'-terminal S fragment is required for replication and modulation of the innate immune response in host cells.

    Science.gov (United States)

    Kloc, Anna; Diaz-San Segundo, Fayna; Schafer, Elizabeth A; Rai, Devendra K; Kenney, Mary; de Los Santos, Teresa; Rieder, Elizabeth

    2017-12-01

    The S fragment of the FMDV 5' UTR is predicted to fold into a long stem-loop structure and it has been implicated in virus-host protein interactions. In this study, we report the minimal S fragment sequence required for virus viability and show a direct correlation between the extent of the S fragment deletion mutations and attenuated phenotypes. Furthermore, we provide novel insight into the role of the S fragment in modulating the host innate immune response. Importantly, in an FMDV mouse model system, all animals survive the inoculation with the live A 24 FMDV-S 4 mutant, containing a 164 nucleotide deletion in the upper S fragment loop, at a dose 1000 higher than the one causing lethality by parental A 24 FMDV, indicating that the A 24 FMDV-S 4 virus is highly attenuated in vivo. Additionally, mice exposed to high doses of live A 24 FMDV-S 4 virus are fully protected when challenged with parental A 24 FMDV virus. Published by Elsevier Inc.

  1. Systems biology of host-mycobiota interactions: dissecting Dectin-1 and Dectin-2 signalling in immune cells with DC-ATLAS.

    Science.gov (United States)

    Rizzetto, Lisa; De Filippo, Carlotta; Rivero, Damariz; Riccadonna, Samantha; Beltrame, Luca; Cavalieri, Duccio

    2013-11-01

    Modelling the networks sustaining the fruitful coexistence between fungi and their mammalian hosts is becoming increasingly important to control emerging fungal pathogens. The C-type lectins Dectin-1 and Dectin-2 are involved in host defense mechanisms against fungal infection driving inflammatory and adaptive immune responses and complement in containing fungal burdens. Recognizing carbohydrate structures in pathogens, their engagement induces maturation of dendritic cells (DCs) into potent immuno-stimulatory cells endowed with the capacity to efficiently prime T cells. Owing to these properties, Dectin-1 and Dectin-2 agonists are currently under investigation as promising adjuvants in vaccination procedures for the treatment of fungal infection. Thus, a detailed understanding of events' cascade specifically triggered in DCs upon engagement is of great interest in translational research. Here, we summarize the current knowledge on Dectin-1 and Dectin-2 signalling in DCs highlighting similarities and differences. Detailed maps are annotated, using the Biological Connection Markup Language (BCML) data model, and stored in DC-ATLAS, a versatile resource for the interpretation of high-throughput data generated perturbing the signalling network of DCs. Copyright © 2013 Elsevier GmbH. All rights reserved.

  2. Genetic variability in G2 and F2 region between biological clones of human respiratory syncytial virus with or without host immune selection pressure

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    Claudia Trigo Pedroso Moraes

    2015-02-01

    Full Text Available Human respiratory syncytial virus (HRSV is an important respiratory pathogens among children between zero-five years old. Host immunity and viral genetic variability are important factors that can make vaccine production difficult. In this work, differences between biological clones of HRSV were detected in clinical samples in the absence and presence of serum collected from children in the convalescent phase of the illness and from their biological mothers. Viral clones were selected by plaque assay in the absence and presence of serum and nucleotide sequences of the G2 and F2 genes of HRSV biological clones were compared. One non-synonymous mutation was found in the F gene (Ile5Asn in one clone of an HRSV-B sample and one non-synonymous mutation was found in the G gene (Ser291Pro in four clones of the same HRSV-B sample. Only one of these clones was obtained after treatment with the child's serum. In addition, some synonymous mutations were determined in two clones of the HRSV-A samples. In conclusion, it is possible that minor sequences could be selected by host antibodies contributing to the HRSV evolutionary process, hampering the development of an effective vaccine, since we verify the same codon alteration in absence and presence of human sera in individual clones of BR-85 sample.

  3. Genetic variability in G2 and F2 region between biological clones of human respiratory syncytial virus with or without host immune selection pressure.

    Science.gov (United States)

    Moraes, Claudia Trigo Pedroso; Oliveira, Danielle Bruna Leal; Campos, Angelica Cristine Almeida; Bosso, Patricia Alves; Lima, Hildener Nogueira; Stewien, Klaus Eberhard; Gilio, Alfredo Elias; Vieira, Sandra Elisabete; Botosso, Viviane Fongaro; Durigon, Edison Luiz

    2015-02-01

    Human respiratory syncytial virus (HRSV) is an important respiratory pathogens among children between zero-five years old. Host immunity and viral genetic variability are important factors that can make vaccine production difficult. In this work, differences between biological clones of HRSV were detected in clinical samples in the absence and presence of serum collected from children in the convalescent phase of the illness and from their biological mothers. Viral clones were selected by plaque assay in the absence and presence of serum and nucleotide sequences of the G2 and F2 genes of HRSV biological clones were compared. One non-synonymous mutation was found in the F gene (Ile5Asn) in one clone of an HRSV-B sample and one non-synonymous mutation was found in the G gene (Ser291Pro) in four clones of the same HRSV-B sample. Only one of these clones was obtained after treatment with the child's serum. In addition, some synonymous mutations were determined in two clones of the HRSV-A samples. In conclusion, it is possible that minor sequences could be selected by host antibodies contributing to the HRSV evolutionary process, hampering the development of an effective vaccine, since we verify the same codon alteration in absence and presence of human sera in individual clones of BR-85 sample.

  4. Listeria monocytogenes CadC Regulates Cadmium Efflux and Fine-tunes Lipoprotein Localization to Escape the Host Immune Response and Promote Infection.

    Science.gov (United States)

    Pombinho, Rita; Camejo, Ana; Vieira, Ana; Reis, Olga; Carvalho, Filipe; Almeida, Maria Teresa; Pinheiro, Jorge Campos; Sousa, Sandra; Cabanes, Didier

    2017-05-01

    Listeria monocytogenes is a major intracellular human foodborne bacterial pathogen. We previously revealed L. monocytogenes cadC as highly expressed during mouse infection. Here we show that L. monocytogenes CadC is a sequence-specific, DNA-binding and cadmium-dependent regulator of CadA, an efflux pump conferring cadmium resistance. CadC but not CadA is required for L. monocytogenes infection in vivo. Interestingly, CadC also directly represses lspB, a gene encoding a lipoprotein signal peptidase whose expression appears detrimental for infection. lspB overexpression promotes the release of the LpeA lipoprotein to the extracellular medium, inducing tumor necrosis factor α and interleukin 6 expression, thus impairing L. monocytogenes survival in macrophages. We propose that L. monocytogenes uses CadC to repress lspB expression during infection to avoid LpeA exposure to the host immune system, diminishing inflammatory cytokine expression and promoting intramacrophagic survival and virulence. CadC appears as the first metal efflux pump regulator repurposed during infection to fine-tune lipoprotein processing and host responses. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  5. Hepatitis B and hepatitis C viruses: a review of viral genomes, viral induced host immune responses, genotypic distributions and worldwide epidemiology

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    Umar Saeed

    2014-04-01

    Full Text Available Hepatitis B and hepatitis C viruses (HCV are frequently propagating blood borne pathogens in global community. Viral hepatitis is primarily associated with severe health complications, such as liver cirrhosis, hepatocellular carcinoma, hepatic fibrosis and steatosis. A literature review was conducted on hepatitis B virus (HBV, HBV genome, genotypic distribution and global epidemiology of HBV, HCV, HCV genome, HCV and host immune responses, HCV genotypic distribution and global epidemiology. The valued information was subjected for review. HBV has strict tissue tropism to liver. The virus infecting hepatocytes produces large amount of hepatitis B surface antigen particles which lack the DNA. It has capability to integrate into host genome. It has been found that genotype C is most emerging genotype associated with more severe liver diseases (cirrhosis. The approximate prevalence rate of genotype C is 27.7% which represents a major threat to future generations. Approximately 8% of population is chronic carrier of HBV in developing countries. The chronic carrier rate of HBV is 2%-7% in Middle East, Eastern and Southern Europe, South America and Japan. Among HCV infected individuals, 15% usually have natural tendency to overcome acute viral infection, where as 85% of individuals were unable to control HCV infection. The internal ribosomal entry site contains highly conserved structures important for binding and appropriate positioning of viral genome inside the host cell. HCV infects only in 1%-10% of hepatocytes, but production of tumor necrosis factor alpha (from CD8+ cells and interferon-gamma cause destruction of both infected cells and non-infected surrounding cells. Almost 11 genotypes and above 100 subtypes of HCV exists worldwide with different geographical distribution. Many efforts are still needed to minimize global burden of these infections. For the complete eradication of HBV (just like small pox and polio via vaccination strategies

  6. Lipopolysaccharides from Commensal and Opportunistic Bacteria: Characterization and Response of the Immune System of the Host Sponge Suberites domuncula

    Science.gov (United States)

    Gardères, Johan; Bedoux, Gilles; Koutsouveli, Vasiliki; Crequer, Sterenn; Desriac, Florie; Le Pennec, Gaël

    2015-01-01

    Marine sponges harbor a rich bacterioflora with which they maintain close relationships. However, the way these animals make the distinction between bacteria which are consumed to meet their metabolic needs and opportunistic and commensal bacteria which are hosted is not elucidated. Among the elements participating in this discrimination, bacterial cell wall components such as lipopolysaccharides (LPS) could play a role. In the present study, we investigated the LPS chemical structure of two bacteria associated with the sponge Suberites domuncula: a commensal Endozoicomonas sp. and an opportunistic Pseudoalteromonas sp. Electrophoretic patterns indicated different LPS structures for these bacteria. The immunomodulatory lipid A was isolated after mild acetic acid hydrolysis. The electrospray ionization ion-trap mass spectra revealed monophosphorylated molecules corresponding to tetra- and pentaacylated structures with common structural features between the two strains. Despite peculiar structural characteristics, none of these two LPS influenced the expression of the macrophage-expressed gene S. domuncula unlike the Escherichia coli ones. Further research will have to include a larger number of genes to understand how this animal can distinguish between LPS with resembling structures and discriminate between bacteria associated with it. PMID:26262625

  7. Timing and severity of immunizing diseases in rabbits is controlled by seasonal matching of host and pathogen dynamics.

    Science.gov (United States)

    Wells, Konstans; Brook, Barry W; Lacy, Robert C; Mutze, Greg J; Peacock, David E; Sinclair, Ron G; Schwensow, Nina; Cassey, Phillip; O'Hara, Robert B; Fordham, Damien A

    2015-02-06

    Infectious diseases can exert a strong influence on the dynamics of host populations, but it remains unclear why such disease-mediated control only occurs under particular environmental conditions. We used 16 years of detailed field data on invasive European rabbits (Oryctolagus cuniculus) in Australia, linked to individual-based stochastic models and Bayesian approximations, to test whether (i) mortality associated with rabbit haemorrhagic disease (RHD) is driven primarily by seasonal matches/mismatches between demographic rates and epidemiological dynamics and (ii) delayed infection (arising from insusceptibility and maternal antibodies in juveniles) are important factors in determining disease severity and local population persistence of rabbits. We found that both the timing of reproduction and exposure to viruses drove recurrent seasonal epidemics of RHD. Protection conferred by insusceptibility and maternal antibodies controlled seasonal disease outbreaks by delaying infection; this could have also allowed escape from disease. The persistence of local populations was a stochastic outcome of recovery rates from both RHD and myxomatosis. If susceptibility to RHD is delayed, myxomatosis will have a pronounced effect on population extirpation when the two viruses coexist. This has important implications for wildlife management, because it is likely that such seasonal interplay and disease dynamics has a strong effect on long-term population viability for many species. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  8. Identification of bovine leukemia virus tax function associated with host cell transcription, signaling, stress response and immune response pathway by microarray-based gene expression analysis

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    Arainga Mariluz

    2012-03-01

    Full Text Available Abstract Background Bovine leukemia virus (BLV is associated with enzootic bovine leukosis and is closely related to human T-cell leukemia virus type I. The Tax protein of BLV is a transcriptional activator of viral replication and a key contributor to oncogenic potential. We previously identified interesting mutant forms of Tax with elevated (TaxD247G or reduced (TaxS240P transactivation effects on BLV replication and propagation. However, the effects of these mutations on functions other than transcriptional activation are unknown. In this study, to identify genes that play a role in the cascade of signal events regulated by wild-type and mutant Tax proteins, we used a large-scale host cell gene-profiling approach. Results Using a microarray containing approximately 18,400 human mRNA transcripts, we found several alterations after the expression of Tax proteins in genes involved in many cellular functions such as transcription, signal transduction, cell growth, apoptosis, stress response, and immune response, indicating that Tax protein has multiple biological effects on various cellular environments. We also found that TaxD247G strongly regulated more genes involved in transcription, signal transduction, and cell growth functions, contrary to TaxS240P, which regulated fewer genes. In addition, the expression of genes related to stress response significantly increased in the presence of TaxS240P as compared to wild-type Tax and TaxD247G. By contrast, the largest group of downregulated genes was related to immune response, and the majority of these genes belonged to the interferon family. However, no significant difference in the expression level of downregulated genes was observed among the Tax proteins. Finally, the expression of important cellular factors obtained from the human microarray results were validated at the RNA and protein levels by real-time quantitative reverse transcription-polymerase chain reaction and western blotting

  9. FTY720 ameliorates murine sclerodermatous chronic graft-versus-host disease by promoting expansion of splenic regulatory cells and inhibiting immune cell infiltration into skin.

    Science.gov (United States)

    Huu, Doanh Le; Matsushita, Takashi; Jin, Guihua; Hamaguchi, Yasuhito; Hasegawa, Minoru; Takehara, Kazuhiko; Fujimoto, Manabu

    2013-06-01

    Sphingosine 1-phosphate (S1P) exerts a variety of activities in immune, inflammatory, and vascular systems. S1P plays an important role in systemic sclerosis (SSc) pathogenesis. Regulation of S1P in fibrotic diseases as well as in SSc was recently reported. FTY720, an oral S1P receptor modulator, has been shown to be a useful agent for the prevention of transplant rejection and autoimmune diseases. Murine sclerodermatous chronic graft-versus-host disease (GVHD) is a model for human sclerodermatous chronic GVHD and SSc. We undertook this study to investigate the effects of FTY720 in murine sclerodermatous chronic GVHD. FTY720 was orally administered to allogeneic recipient mice from day 0 to day 20 (short-term, early-treatment group), from day 0 to day 42 (full-term, early-treatment group), or from day 22 to day 42 (delayed-treatment group) after bone marrow transplantation. Delayed administration of FTY720 attenuated, and early administration of FTY720 inhibited, the severity and fibrosis in murine sclerodermatous chronic GVHD. With early treatment, FTY720 induced expansion of splenic myeloid-derived suppressor cells, Treg cells, and Breg cells. Vascular damage in chronic GVHD was inhibited by FTY720 through down-regulating serum levels of S1P and soluble E-selectin. FTY720 inhibited infiltration of immune cells into skin. Moreover, FTY720 diminished the expression of messenger RNA for monocyte chemotactic protein 1, macrophage inflammatory protein 1α, RANTES, tumor necrosis factor α, interferon-γ, interleukin-6 (IL-6), IL-10, IL-17A, and transforming growth factor β1 in the skin. FTY720 suppressed the immune response by promoting the expansion of regulatory cells and reducing vascular damage and infiltration of immune cells into the skin. Taken together, these results have important implications for the potential use of FTY720 in the treatment of sclerodermatous chronic GVHD and SSc in humans. Copyright © 2013 by the American College of Rheumatology.

  10. Plant innate immunity induced by flagellin suppresses the hypersensitive response in non-host plants elicited by Pseudomonas syringae pv. averrhoi.

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    Chia-Fong Wei

    Full Text Available A new pathogen, Pseudomonas syringae pv. averrhoi (Pav, which causes bacterial spot disease on carambola was identified in Taiwan in 1997. Many strains of this pathovar have been isolated from different locations and several varieties of hosts. Some of these strains, such as HL1, are nonmotile and elicit a strong hypersensitive response (HR in nonhost tobacco leaves, while other strains, such as PA5, are motile and elicit a weak HR. Based on the image from a transmission electron microscope, the results showed that HL1 is flagellum-deficient and PA5 has normal flagella. Here we cloned and analyzed the fliC gene and glycosylation island from Pav HL1 and PA5. The amino acid sequences of FliC from HL1 and PA5 are identical to P. s. pvs. tabaci (Pta, glycinea and phaseolicola and share very high similarity with other pathovars of P. syringae. In contrast to the flagellin mutant PtaΔfliC, PA5ΔfliC grows as well as wild type in the host plant, but it elicits stronger HR than wild type does in non-host plants. Furthermore, the purified Pav flagellin, but not the divergent flagellin from Agrobacterium tumefaciens, is able to impair the HR induced by PA5ΔfliC. PA5Δfgt1 possessing nonglycosylated flagella behaved as its wild type in both bacterial growth in host and HR elicitation. Flagellin was infiltrated into tobacco leaves either simultaneously with flagellum-deficient HL1 or prior to the inoculation of wild type HL1, and both treatments impaired the HR induced by HL1. Moreover, the HR elicited by PA5 and PA5ΔfliC was enhanced by the addition of cycloheximide, suggesting that the flagellin is one of the PAMPs (pathogen-associated molecular patterns contributed to induce the PAMP-triggered immunity (PTI. Taken together, the results shown in this study reveal that flagellin in Pav is capable of suppressing HR via PTI induction during an incompatible interaction.

  11. Plant Innate Immunity Induced by Flagellin Suppresses the Hypersensitive Response in Non-Host Plants Elicited by Pseudomonas syringae pv. averrhoi

    Science.gov (United States)

    Wei, Chia-Fong; Hsu, Shih-Tien; Deng, Wen-Ling; Wen, Yu-Der; Huang, Hsiou-Chen

    2012-01-01

    A new pathogen, Pseudomonas syringae pv. averrhoi (Pav), which causes bacterial spot disease on carambola was identified in Taiwan in 1997. Many strains of this pathovar have been isolated from different locations and several varieties of hosts. Some of these strains, such as HL1, are nonmotile and elicit a strong hypersensitive response (HR) in nonhost tobacco leaves, while other strains, such as PA5, are motile and elicit a weak HR. Based on the image from a transmission electron microscope, the results showed that HL1 is flagellum-deficient and PA5 has normal flagella. Here we cloned and analyzed the fliC gene and glycosylation island from Pav HL1 and PA5. The amino acid sequences of FliC from HL1 and PA5 are identical to P. s. pvs. tabaci (Pta), glycinea and phaseolicola and share very high similarity with other pathovars of P. syringae. In contrast to the flagellin mutant PtaΔfliC, PA5ΔfliC grows as well as wild type in the host plant, but it elicits stronger HR than wild type does in non-host plants. Furthermore, the purified Pav flagellin, but not the divergent flagellin from Agrobacterium tumefaciens, is able to impair the HR induced by PA5ΔfliC. PA5Δfgt1 possessing nonglycosylated flagella behaved as its wild type in both bacterial growth in host and HR elicitation. Flagellin was infiltrated into tobacco leaves either simultaneously with flagellum-deficient HL1 or prior to the inoculation of wild type HL1, and both treatments impaired the HR induced by HL1. Moreover, the HR elicited by PA5 and PA5ΔfliC was enhanced by the addition of cycloheximide, suggesting that the flagellin is one of the PAMPs (pathogen-associated molecular patterns) contributed to induce the PAMP-triggered immunity (PTI). Taken together, the results shown in this study reveal that flagellin in Pav is capable of suppressing HR via PTI induction during an incompatible interaction. PMID:22911741

  12. PSGL-1 on Leukocytes is a Critical Component of the Host Immune Response against Invasive Pneumococcal Disease.

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    Elisa Ramos-Sevillano

    2016-03-01

    Full Text Available Bacterial uptake by phagocytic cells is a vital event in the clearance of invading pathogens such as Streptococcus pneumoniae. A major role of the P-selectin glycoprotein ligand-1 (PSGL-1 on leukocytes against invasive pneumococcal disease is described in this study. Phagocytosis experiments using different serotypes demonstrated that PSGL-1 is involved in the recognition, uptake and killing of S. pneumoniae. Co-localization of several clinical isolates of S. pneumoniae with PSGL-1 was demonstrated, observing a rapid and active phagocytosis in the presence of PSGL-1. Furthermore, the pneumococcal capsular polysaccharide and the main autolysin of the bacterium--the amidase LytA--were identified as bacterial ligands for PSGL-1. Experimental models of pneumococcal disease including invasive pneumonia and systemic infection showed that bacterial levels were markedly increased in the blood of PSGL-1-/- mice. During pneumonia, PSGL-1 controls the severity of pneumococcal dissemination from the lung to the bloodstream. In systemic infection, a major role of PSGL-1 in host defense is to clear the bacteria in the systemic circulation controlling bacterial replication. These results confirmed the importance of this receptor in the recognition and clearance of S. pneumoniae during invasive pneumococcal disease. Histological and cellular analysis demonstrated that PSGL-1-/- mice have increased levels of T cells migrating to the lung than the corresponding wild-type mice. In contrast, during systemic infection, PSGL-1-/- mice had increased numbers of neutrophils and macrophages in blood, but were less effective controlling the infection process due to the lack of this functional receptor. Overall, this study demonstrates that PSGL-1 is a novel receptor for S. pneumoniae that contributes to protection against invasive pneumococcal disease.

  13. Postoperative spinal column; Postoperative Wirbelsaeule

    Energy Technology Data Exchange (ETDEWEB)

    Kaefer, W. [Westpfalzklinikum GmbH, Standort II, Abteilung fuer Wirbelsaeulenchirurgie, Kusel (Germany); Heumueller, I. [Westpfalzklinikum GmbH, Standort II, Institut fuer Radiologie II, Kusel (Germany); Harsch, N.; Kraus, C.; Reith, W. [Universitaetsklinikum des Saarlandes, Klinik fuer Diagnostische und Interventionelle Neuroradiologie, Homburg/Saar (Germany)

    2016-08-15

    As a rule, postoperative imaging is carried out after spinal interventions to document the exact position of the implant material. Imaging is absolutely necessary when new clinical symptoms occur postoperatively. In this case a rebleeding or an incorrect implant position abutting a root or the spinal cord must be proven. In addition to these immediately occurring postoperative clinical symptoms, there are a number of complications that can occur several days, weeks or even months later. These include the failed back surgery syndrome, implant loosening or breakage of the material and relapse of a disc herniation and spondylodiscitis. In addition to knowledge of the original clinical symptoms, it is also important to know the operation details, such as the access route and the material used. In almost all postoperative cases, imaging with contrast medium administration and corresponding correction of artefacts by the implant material, such as the dual energy technique, correction algorithms and the use of special magnetic resonance (MR) sequences are necessary. In order to correctly assess the postoperative imaging, knowledge of the surgical procedure and the previous clinical symptoms are mandatory besides special computed tomography (CT) techniques and MR sequences. (orig.) [German] In der Regel erfolgt bei spinalen Eingriffen eine postoperative Bildgebung, um die exakte Lage des Implantatmaterials zu dokumentieren. Unbedingt notwendig ist die Bildgebung, wenn postoperativ neue klinische Symptome aufgetreten sind. Hier muessen eine Nachblutung bzw. inkorrekte, eine Wurzel oder das Myelon tangierende Implantatlage nachgewiesen werden. Neben diesen direkt postoperativ auftretenden klinischen Symptomen gibt es eine Reihe von Komplikationen, die erst nach mehreren Tagen, Wochen oder sogar nach Monaten auftreten koennen. Hierzu zaehlen das Failed-back-surgery-Syndrom, die Implantatlockerung oder -bruch, aber auch ein Rezidivvorfall und die Spondylodiszitis. Neben der

  14. Lactobacillus johnsonii N6.2 Modulates the Host Immune Responses: A Double-Blind, Randomized Trial in Healthy Adults

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    Guillermo E. Marcial

    2017-06-01

    Full Text Available Lactobacillus johnsonii N6.2 mitigates the onset of type 1 diabetes (T1D in biobreeding diabetes-prone rats, in part, through changes in kynurenine:tryptophan (K:T ratios. The goal of this pilot study was to determine the safety, tolerance, and general immunological response of L. johnsonii N6.2 in healthy subjects. A double-blind, randomized clinical trial in 42 healthy individuals with no known risk factors for T1D was undertaken to evaluate subject responses to the consumption of L. johnsonii N6.2. Participants received 1 capsule/day containing 108 colony-forming units of L. johnsonii N6.2 or placebo for 8 weeks. Comprehensive metabolic panel (CMP, leukocyte subpopulations by complete blood count (CBC and flow cytometry, serum cytokines, and relevant metabolites in the indoleamine-2,3-dioxygenase pathway were assessed. L. johnsonii N6.2 survival and intestinal microbiota was analyzed. Daily and weekly questionnaires were assessed for potential effects of probiotic treatment on general wellness. The administration of L. johnsonii N6.2 did not modify the CMP or CBC of participants suggesting general safety. In fact, L. johnsonii N6.2 administration significantly decreased the occurrence of abdominal pain, indigestion, and cephalic syndromes. As predicted, increased serum tryptophan levels increased resulting in a decreased K:T ratio was observed in the L. johnsonii N6.2 group. Interestingly, immunophenotyping assays revealed that monocytes and natural killer cell numbers were increased significantly after washout (12 weeks. Moreover, an increase of circulating effector Th1 cells (CD45RO+CD183+CD196− and cytotoxic CD8+ T cells subset was observed in the L. johnsonii N6.2 group. Consumption of L. johnsonii N6.2 is well tolerated in adult control subjects, demonstrates systemic impacts on innate and adaptive immune populations, and results in a decreased K:T ratio. These data provide support for the safety and feasibility of using L

  15. An Interferon Regulated MicroRNA Provides Broad Cell-Intrinsic Antiviral Immunity through Multihit Host-Directed Targeting of the Sterol Pathway

    Science.gov (United States)

    Robertson, Kevin A.; Hsieh, Wei Yuan; Forster, Thorsten; Blanc, Mathieu; Lu, Hongjin; Crick, Peter J.; Yutuc, Eylan; Watterson, Steven; Martin, Kimberly; Griffiths, Samantha J.; Enright, Anton J.; Yamamoto, Mami; Pradeepa, Madapura M.; Lennox, Kimberly A.; Behlke, Mark A.; Talbot, Simon; Haas, Jürgen; Dölken, Lars; Griffiths, William J.; Wang, Yuqin; Angulo, Ana; Ghazal, Peter

    2016-01-01

    In invertebrates, small interfering RNAs are at the vanguard of cell-autonomous antiviral immunity. In contrast, antiviral mechanisms initiated by interferon (IFN) signaling predominate in mammals. Whilst mammalian IFN-induced miRNA are known to inhibit specific viruses, it is not known whether host-directed microRNAs, downstream of IFN-signaling, have a role in mediating broad antiviral resistance. By performing an integrative, systematic, global analysis of RNA turnover utilizing 4-thiouridine labeling of newly transcribed RNA and pri/pre-miRNA in IFN-activated macrophages, we identify a new post-transcriptional viral defense mechanism mediated by miR-342-5p. On the basis of ChIP and site-directed promoter mutagenesis experiments, we find the synthesis of miR-342-5p is coupled to the antiviral IFN response via the IFN-induced transcription factor, IRF1. Strikingly, we find miR-342-5p targets mevalonate-sterol biosynthesis using a multihit mechanism suppressing the pathway at different functional levels: transcriptionally via SREBF2, post-transcriptionally via miR-33, and enzymatically via IDI1 and SC4MOL. Mass spectrometry-based lipidomics and enzymatic assays demonstrate the targeting mechanisms reduce intermediate sterol pathway metabolites and total cholesterol in macrophages. These results reveal a previously unrecognized mechanism by which IFN regulates the sterol pathway. The sterol pathway is known to be an integral part of the macrophage IFN antiviral response, and we show that miR-342-5p exerts broad antiviral effects against multiple, unrelated pathogenic viruses such Cytomegalovirus and Influenza A (H1N1). Metabolic rescue experiments confirm the specificity of these effects and demonstrate that unrelated viruses have differential mevalonate and sterol pathway requirements for their replication. This study, therefore, advances the general concept of broad antiviral defense through multihit targeting of a single host pathway. PMID:26938778

  16. An Interferon Regulated MicroRNA Provides Broad Cell-Intrinsic Antiviral Immunity through Multihit Host-Directed Targeting of the Sterol Pathway.

    Directory of Open Access Journals (Sweden)

    Kevin A Robertson

    2016-03-01

    Full Text Available In invertebrates, small interfering RNAs are at the vanguard of cell-autonomous antiviral immunity. In contrast, antiviral mechanisms initiated by interferon (IFN signaling predominate in mammals. Whilst mammalian IFN-induced miRNA are known to inhibit specific viruses, it is not known whether host-directed microRNAs, downstream of IFN-signaling, have a role in mediating broad antiviral resistance. By performing an integrative, systematic, global analysis of RNA turnover utilizing 4-thiouridine labeling of newly transcribed RNA and pri/pre-miRNA in IFN-activated macrophages, we identify a new post-transcriptional viral defense mechanism mediated by miR-342-5p. On the basis of ChIP and site-directed promoter mutagenesis experiments, we find the synthesis of miR-342-5p is coupled to the antiviral IFN response via the IFN-induced transcription factor, IRF1. Strikingly, we find miR-342-5p targets mevalonate-sterol biosynthesis using a multihit mechanism suppressing the pathway at different functional levels: transcriptionally via SREBF2, post-transcriptionally via miR-33, and enzymatically via IDI1 and SC4MOL. Mass spectrometry-based lipidomics and enzymatic assays demonstrate the targeting mechanisms reduce intermediate sterol pathway metabolites and total cholesterol in macrophages. These results reveal a previously unrecognized mechanism by which IFN regulates the sterol pathway. The sterol pathway is known to be an integral part of the macrophage IFN antiviral response, and we show that miR-342-5p exerts broad antiviral effects against multiple, unrelated pathogenic viruses such Cytomegalovirus and Influenza A (H1N1. Metabolic rescue experiments confirm the specificity of these effects and demonstrate that unrelated viruses have differential mevalonate and sterol pathway requirements for their replication. This study, therefore, advances the general concept of broad antiviral defense through multihit targeting of a single host pathway.

  17. Postoperative hypoparathyroidism

    International Nuclear Information System (INIS)

    Rao, R.S.

    1999-01-01

    It is essential to preserve as many of the parathyroid glands, as possible, during surgery of the thyroid gland. This is achieved by visualizing them and by minimal handling of the glands. Truncal ligation of the inferior thyroid artery is quite safe. Capsular ligation of the branches of the artery is theoretically superior but requires a greater degree of skill and experience in thyroid surgery. It also puts the recurrent laryngeal nerve at a greater risk of injury. Calcitriol or 1.25 dihydroxy vitamin D is a very useful drug in managing patients with severe post-operative hypoparathyroidism

  18. Meta-analysis of the effects of insect vector saliva on host immune responses and infection of vector-transmitted pathogens: a focus on leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Brittany Ockenfels

    2014-10-01

    Full Text Available A meta-analysis of the effects of vector saliva on the immune response and progression of vector-transmitted disease, specifically with regard to pathology, infection level, and host cytokine levels was conducted. Infection in the absence or presence of saliva in naïve mice was compared. In addition, infection in mice pre-exposed to uninfected vector saliva was compared to infection in unexposed mice. To control for differences in vector and pathogen species, mouse strain, and experimental design, a random effects model was used to compare the ratio of the natural log of the experimental to the control means of the studies. Saliva was demonstrated to enhance pathology, infection level, and the production of Th2 cytokines (IL-4 and IL-10 in naïve mice. This effect was observed across vector/pathogen pairings, whether natural or unnatural, and with single salivary proteins used as a proxy for whole saliva. Saliva pre-exposure was determined to result in less severe leishmaniasis pathology when compared with unexposed mice infected either in the presence or absence of sand fly saliva. The results of further analyses were not significant, but demonstrated trends toward protection and IFN-γ elevation for pre-exposed mice.

  19. Meta-analysis of the effects of insect vector saliva on host immune responses and infection of vector-transmitted pathogens: a focus on leishmaniasis.

    Science.gov (United States)

    Ockenfels, Brittany; Michael, Edwin; McDowell, Mary Ann

    2014-10-01

    A meta-analysis of the effects of vector saliva on the immune response and progression of vector-transmitted disease, specifically with regard to pathology, infection level, and host cytokine levels was conducted. Infection in the absence or presence of saliva in naïve mice was compared. In addition, infection in mice pre-exposed to uninfected vector saliva was compared to infection in unexposed mice. To control for differences in vector and pathogen species, mouse strain, and experimental design, a random effects model was used to compare the ratio of the natural log of the experimental to the control means of the studies. Saliva was demonstrated to enhance pathology, infection level, and the production of Th2 cytokines (IL-4 and IL-10) in naïve mice. This effect was observed across vector/pathogen pairings, whether natural or unnatural, and with single salivary proteins used as a proxy for whole saliva. Saliva pre-exposure was determined to result in less severe leishmaniasis pathology when compared with unexposed mice infected either in the presence or absence of sand fly saliva. The results of further analyses were not significant, but demonstrated trends toward protection and IFN-γ elevation for pre-exposed mice.

  20. Persistent hepatitis virus infection and immune homeostasis

    OpenAIRE

    ZHOU Yun

    2014-01-01

    Homeostasis between the host and viruses is naturally maintained. On the one hand, the immune system activates the immune response to kill or eliminate viruses; on the other hand, the immune system controls the immune response to maintain immune homeostasis. The cause of persistent infections with hepatitis viruses such as HBV and HCV is that viral molecules damage the immune system of the host and their variants escape immune clearance. Long-term coexistence of the host and viruses is the pr...

  1. Ranitidine prevents postoperative transfusion-induced depression of delayed hypersensitivity

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Hammer, J H; Moesgaard, F

    1989-01-01

    The influence of perioperative blood transfusion on postoperative depression of cell-mediated immunity (CMI) and the effect of ranitidine on transfusion-induced changes in postoperative CMI were investigated. CMI was assessed preoperatively and postoperatively by skin testing with seven common...

  2. Host Adaptation of Staphylococcal Leukocidins

    NARCIS (Netherlands)

    Vrieling, M

    2016-01-01

    Staphylococcus aureus is a human and animal pathogen of global importance and has the capacity to cause disease in distinct host populations, using a large arsenal of secreted proteins to evade the host immune response. Amongst the immune evasion proteins of S. aureus, secreted cytotoxins play a

  3. Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis | Center for Cancer Research

    Science.gov (United States)

    We demonstrate a novel tumor-promoting role of myeloid immune suppressor Gr+CD11b+ cells, which are evident in cancer patients and tumor-bearing animals. These cells constitute approximately 5% of total cells in tumors. Tumors coinjected with Gr+CD11b+ cells exhibited increased vascular density, vascular maturation, and decreased necrosis. These immune cells produce high

  4. The Brachypodium-Puccinia graminis system: Solving a puzzle to uncover the underlying mechanisms of non-host resistance and plant immunity

    Science.gov (United States)

    Brachypodium distachyon is regarded as non-host to the causal agent of stem rust in wheat and barley, P. graminis f. sp. tritici (Pgt), and a near-host to the pathogens of forage grasses, P. graminis f. sp. lolii (Pgl) and P. graminis f. sp. phlei-pratensis (Pgp). Given the devastating effect of ste...

  5. Experimentally-induced immune activation in natural hosts of SIV induces significant increases in viral replication and CD4+ T cell depletion

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, Ruy M [Los Alamos National Laboratory

    2008-01-01

    Chronically SIVagm-infected African green monkeys (AGMs) have a remarkably stable non-pathogenic disease course, with levels of immune activation in chronic SIVagm infection similar to those observed in uninfected monkeys and stable viral loads (VLs) for long periods of time. In vivo administration of lipopolysaccharide (LPS) or an IL-2/diphtheria toxin fusion protein (Ontak) to chronically SIVagm-infected AGMs triggered increases in immune activation and subsequently of viral replication and depletion of intestinal CD4{sup +} T cells. Our study indicates that circulating microbial products can increase viral replication by inducing immune activation and increasing the number of viral target cells, thus demonstrating that immune activation and T cell prolifeation are key factors in AIDS pathogenesis.

  6. Evidence for suppression of immunity as a driver for genomic introgressions and host range expansion in races of Albugo candida, a generalist parasite

    DEFF Research Database (Denmark)

    McMullan, Mark; Gardiner, Anastasia; Bailey, Kate

    2015-01-01

    How generalist parasites with wide host ranges can evolve is a central question in parasite evolution. Albugo candida is an obligate biotrophic parasite that consists of many physiological races that each specialize on distinct Brassicaceae host species. By analyzing genome sequence assemblies...... by normally non-infecting races. This facilitates introgression and the exchange of effector repertoires, and may enable the evolution of novel races that can undergo clonal population expansion on new hosts. We discuss recent studies on hybridization in other eukaryotes such as yeast, Heliconius butterflies...

  7. Host age modulates within-host parasite competition.

    Science.gov (United States)

    Izhar, Rony; Routtu, Jarkko; Ben-Ami, Frida

    2015-05-01

    In many host populations, one of the most striking differences among hosts is their age. While parasite prevalence differences in relation to host age are well known, little is known on how host age impacts ecological and evolutionary dynamics of diseases. Using two clones of the water flea Daphnia magna and two clones of its bacterial parasite Pasteuria ramosa, we examined how host age at exposure influences within-host parasite competition and virulence. We found that multiply-exposed hosts were more susceptible to infection and suffered higher mortality than singly-exposed hosts. Hosts oldest at exposure were least often infected and vice versa. Furthermore, we found that in young multiply-exposed hosts competition was weak, allowing coexistence and transmission of both parasite clones, whereas in older multiply-exposed hosts competitive exclusion was observed. Thus, age-dependent parasite exposure and host demography (age structure) could together play an important role in mediating parasite evolution. At the individual level, our results demonstrate a previously unnoticed interaction of the host's immune system with host age, suggesting that the specificity of immune function changes as hosts mature. Therefore, evolutionary models of parasite virulence might benefit from incorporating age-dependent epidemiological parameters. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  8. Viral immune evasion: a masterpiece of evolution

    NARCIS (Netherlands)

    Vossen, Mireille T. M.; Westerhout, Ellen M.; Söderberg-Nauclér, Cécilia; Wiertz, Emmanuel J. H. J.

    2002-01-01

    Coexistence of viruses and their hosts imposes an evolutionary pressure on both the virus and the host immune system. On the one hand, the host has developed an immune system able to attack viruses and virally infected cells, whereas on the other hand, viruses have developed an array of immune

  9. Vaccination of koalas (Phascolarctos cinereus) with a recombinant chlamydial major outer membrane protein adjuvanted with poly I:C, a host defense peptide and polyphosphazine, elicits strong and long lasting cellular and humoral immune responses.

    Science.gov (United States)

    Khan, Shahneaz Ali; Waugh, Courtney; Rawlinson, Galit; Brumm, Jacqui; Nilsson, Karen; Gerdts, Volker; Potter, Andrew; Polkinghorne, Adam; Beagley, Kenneth; Timms, Peter

    2014-10-07

    Chlamydial infections are wide spread in koalas across their range and a solution to this debilitating disease has been sought for over a decade. Antibiotics are the currently accepted therapeutic measure, but are not an effective treatment due to the asymptomatic nature of some infections and a low efficacy rate. Thus, a vaccine would be an ideal way to address this infectious disease threat in the wild. Previous vaccine trials have used a three-dose regimen; however this is very difficult to apply in the field as it would require multiple capture events, which are stressful and invasive processes for the koala. In addition, it requires skilled koala handlers and a significant monetary investment. To overcome these challenges, in this study we utilized a polyphosphazine based poly I:C and a host defense peptide adjuvant combined with recombinant chlamydial major outer membrane protein (rMOMP) antigen to induce long lasting (54 weeks) cellular and humoral immunity in female koalas with a novel single immunizing dose. Immunized koalas produced a strong IgG response in plasma, as well as at mucosal sites. Moreover, they showed high levels of C. pecorum specific neutralizing antibodies in the plasma as well as vaginal and conjunctival secretions. Lastly, Chlamydia-specific lymphocyte proliferation responses were produced against both whole chlamydial elementary bodies and rMOMP protein, over the 12-month period. The results of this study suggest that a single dose rMOMP vaccine incorporating a poly I:C, host defense peptide and polyphosphazine adjuvant is able to stimulate both arms of the immune system in koalas, thereby providing an alternative to antibiotic treatment and/or a three-dose vaccine regime. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Host immune status affects maturation time in two nematode species--but not as predicted by a simple life-history model.

    Science.gov (United States)

    Guinnee, M A; Gemmill, A W; Chan, B H K; Viney, M E; Read, A F

    2003-11-01

    In theory, the age at which maturation occurs in parasitic nematodes is inversely related to pre-maturational mortality rate, and cross-species data on mammalian nematodes are consistent with this prediction. Immunity is a major source of parasite mortality and parasites stand to gain sizeable fitness benefits through short-term adjustments of maturation time in response to variation in immune-mediated mortality. The effects of thymus-dependent immune responses on maturation in the nematode parasites Strongyloides ratti and Nippostrongylus brasiliensis were investigated using congenitally thymus-deficient (nude) rats. As compared with worms in normal rats, reproductive maturity of parasites (presence of eggs in utero) in nude rats occurred later in S. ratti but earlier in N. brasiliensis. Immune-mediated differences in maturation time were not associated with differences in worm length. Thymus-dependent immunity had no effect on prematurational mortality. Results are discussed in relation to theoretical expectations and possible explanations for the observed patterns in parasite maturation.

  11. Immunonutrition ? the influence of early postoperative glutamine supplementation in enteral/parenteral nutrition on immune response, wound healing and length of hospital stay in multiple trauma patients and patients after extensive surgery

    OpenAIRE

    Lorenz, Kai J.; Schallert, Reiner; Daniel, Volker

    2015-01-01

    Introduction: In the postoperative phase, the prognosis of multiple trauma patients with severe brain injuries as well as of patients with extensive head and neck surgery mainly depends on protein metabolism and the prevention of septic complications. Wound healing problems can also result in markedly longer stays in the intensive care unit and general wards. As a result, the immunostimulation of patients in the postoperative phase is expected to improve their immunological and overall healt...

  12. Foot-and-mouth disease virus 5’-terminal S fragment is required for replication and modulation of the innate immune response in host cells

    Science.gov (United States)

    The foot-and-mouth disease virus (FMDV) contains a 5’ untranslated region (5’UTR) with multiple structural domains that regulate viral genome replication, translation, and virus-host interactions. At its 5’terminus, the S fragment of over 360 bp is predicted to form a stable stem-loop that is separ...

  13. Anti-Aspergillus human host defence relies on type 1 T helper (Th1), rather than type 17 T helper (Th17), cellular immunity

    NARCIS (Netherlands)

    L.Y.A. Chai (Louis); F. van de Veerdonk (Frank); R.J. Marijnissen (Renoud); S.C. Cheng (Shih-Chin); A.L. Khoo; M. Hectors (Magda); K. Lagrou (Katrien); A.G. Vonk (Alieke); J. Maertens (Johan); L.A.B. Joosten (Leo); B.J. Kullberg (Bart Jan); M.G. Netea (Mihai)

    2010-01-01

    textabstractSummary Both interferon-γ-producing type 1 T helper (Th1)- and interleukin-17 (IL-17)-producing Th17 cells have been proposed to be involved in anti-fungal host defence. Although invasive aspergillosis is one of the most severe human fungal infections, little is known regarding the

  14. Aspergillus flavus infection triggered immune responses and host-pathogen cross-talks in groundnut during in-vitro seed colonization

    Science.gov (United States)

    Aflatoxin contamination, caused by fungal pathogen Aspergillus flavus, is a major quality and health problem delimiting the trade and consumption of groundnut (Arachis hypogaea L.) worldwide. RNA-seq approach was deployed to understand the host-pathogen interaction by identifying differentially expr...

  15. Vaccination with an Attenuated Mutant of Ehrlichia chaffeensis Induces Pathogen-Specific CD4+ T Cell Immunity and Protection from Tick-Transmitted Wild-Type Challenge in the Canine Host.

    Directory of Open Access Journals (Sweden)

    Jodi L McGill

    Full Text Available Ehrlichia chaffeensis is a tick-borne rickettsial pathogen and the causative agent of human monocytic ehrlichiosis. Transmitted by the Amblyomma americanum tick, E. chaffeensis also causes disease in several other vertebrate species including white-tailed deer and dogs. We have recently described the generation of an attenuated mutant strain of E. chaffeensis, with a mutation in the Ech_0660 gene, which is able to confer protection from secondary, intravenous-administered, wild-type E. chaffeensis infection in dogs. Here, we extend our previous results, demonstrating that vaccination with the Ech_0660 mutant protects dogs from physiologic, tick-transmitted, secondary challenge with wild-type E. chaffeensis; and describing, for the first time, the cellular and humoral immune responses induced by Ech_0660 mutant vaccination and wild-type E. chaffeensis infection in the canine host. Both vaccination and infection induced a rise in E. chaffeensis-specific antibody titers and a significant Th1 response in peripheral blood as measured by E. chaffeensis antigen-dependent CD4+ T cell proliferation and IFNγ production. Further, we describe for the first time significant IL-17 production by peripheral blood leukocytes from both Ech_0660 mutant vaccinated animals and control animals infected with wild-type E. chaffeensis, suggesting a previously unrecognized role for IL-17 and Th17 cells in the immune response to rickettsial pathogens. Our results are a critical first step towards defining the role of the immune system in vaccine-induced protection from E. chaffeensis infection in an incidental host; and confirm the potential of the attenuated mutant clone, Ech_0660, to be used as a vaccine candidate for protection against tick-transmitted E. chaffeensis infection.

  16. Postoperative ileus involves interleukin-1 receptor signaling in enteric glia

    NARCIS (Netherlands)

    Stoffels, Burkhard; Hupa, Kristof Johannes; Snoek, Susanne A.; van Bree, Sjoerd; Stein, Kathy; Schwandt, Timo; Vilz, Tim O.; Lysson, Mariola; Veer, Cornelis Van't; Kummer, Markus P.; Hornung, Veit; Kalff, Joerg C.; de Jonge, Wouter J.; Wehner, Sven

    2014-01-01

    Postoperative ileus (POI) is a common consequence of abdominal surgery that increases the risk of postoperative complications and morbidity. We investigated the cellular mechanisms and immune responses involved in the pathogenesis of POI. We studied a mouse model of POI in which intestinal

  17. Cofactor Independent Phosphoglycerate Mutase of Brugia malayi Induces a Mixed Th1/Th2 Type Immune Response and Inhibits Larval Development in the Host

    Directory of Open Access Journals (Sweden)

    Prashant K. Singh

    2014-01-01

    Full Text Available Lymphatic filariasis is a major debilitating disease, endemic in 72 countries putting more than 1.39 billion people at risk and 120 million are already infected. Despite the significant progress in chemotherapeutic advancements, there is still need for other measures like development of an effective vaccine or discovery of novel drug targets. In this study, structural and immunological characterization of independent phosphoglycerate mutase of filarial parasite Brugia malayi was carried out. Protein was found to be expressed in all major parasite life stages and as an excretory secretory product of adult parasites. Bm-iPGM also reacted to all the categories of human bancroftian patient’s sera including endemic normals. In vivo immunological behaviour of protein was determined in immunized BALB/c mice followed by prophylactic analysis in BALB/c mice and Mastomys coucha. Immunization with Bm-iPGM led to generation of a mixed Th1/Th2 type immune response offering 58.2% protection against larval challenge in BALB/c and 65–68% protection in M. coucha. In vitro studies confirmed participation of anti-Bm-iPGM antibodies in killing of B. malayi infective larvae and microfilariae through ADCC mechanism. The present findings reveal potential immunoprotective nature of Bm-iPGM advocating its worth as an antifilarial vaccine candidate.

  18. HIV-1-negative female sex workers sustain high cervical IFNɛ, low immune activation, and low expression of HIV-1-required host genes.

    Science.gov (United States)

    Abdulhaqq, S A; Zorrilla, C; Kang, G; Yin, X; Tamayo, V; Seaton, K E; Joseph, J; Garced, S; Tomaras, G D; Linn, K A; Foulkes, A S; Azzoni, L; VerMilyea, M; Coutifaris, C; Kossenkov, A V; Showe, L; Kraiselburd, E N; Li, Q; Montaner, L J

    2016-07-01

    Sex workers practicing in high HIV endemic areas have been extensively targeted to test anti-HIV prophylactic strategies. We hypothesize that in women with high levels of genital exposure to semen changes in cervico-vaginal mucosal and/or systemic immune activation will contribute to a decreased susceptibility to HIV-1 infection. To address this question, we assessed sexual activity and immune activation status (in peripheral blood), as well as cellular infiltrates and gene expression in ectocervical mucosa biopsies in female sex workers (FSWs; n=50), as compared with control women (CG; n=32). FSWs had low-to-absent HIV-1-specific immune responses with significantly lower CD38 expression on circulating CD4(+) or CD8(+) T-cells (both: PHIV-1 integration and replication. A correlative relationship between semen exposure and elevated type-1 IFN expression in FSWs was also established. Overall, our data suggest that long-term condomless sex work can result in multiple changes within the cervico-vaginal compartment that would contribute to sustaining a lower susceptibility for HIV-1 infection in the absence of HIV-specific responses.

  19. Latent microsporidiosis caused by Encephalitozoon cuniculi in immunocompetent hosts: a murine model demonstrating the ineffectiveness of the immune system and treatment with albendazole.

    Directory of Open Access Journals (Sweden)

    Michaela Kotkova

    Full Text Available BACKGROUND: Microsporidia are obligate intracellular parasites causing severe infections with lethal outcome in immunocompromised hosts. However, these pathogens are more frequently reported as latent infections in immunocompetent individuals and raises questions about the potential risk of reactivation following induced immunosuppression. AIMS: To evaluate the possibility latent microsporidiosis, efficacy or albendazole, and reactivation, the authors monitored the course of E. cuniculi infection in immunocompetent BALB/c mice and immunodeficient SCID mice using molecular methods. METHODS: Mice were per orally infected with 10(7 spores of E. cuniculi. Selected groups were treated with albendazole, re-infected or chemically immunosuppressed by dexamethasone. The presence of microsporidia in the host's organs and feces were determined using PCR methods. Changes in numbers of lymphocytes in blood and in spleen after induction of immunosuppression were confirmed using flow cytometry analysis. RESULTS: Whereas E. cuniculi caused lethal microsporidiosis in SCID mice, the infection in BABL/c mice remained asymptomatic despite parasite dissemination into many organs during the acute infection phase. Albendazole treatment led to microsporidia elimination from organs in BALB/c mice. In SCID mice, however, only a temporary reduction in number of affected organs was observed and infection re-established post-treatment. Dexamethasone treatment resulted in a chronic microsporidia infection disseminating into most organs in BALB/c mice. Although the presence of E. cuniculi in organs of albendazole- treated mice was undetectable by PCR, it was striking that infection was reactivated by immunosuppression treatment. CONCLUSION: Our results demonstrated that microsporidia can successfully survive in organs of immunocompetent hosts and are able to reactivate from undetectable levels and spread within these hosts after induction of immunosuppression. These findings

  20. Association of immunity and tolerance of host H-2 determinants in irradiated F1 hybrid mice reconstituted with bone marrow cells from one parental strain

    International Nuclear Information System (INIS)

    Sprent, J.; von Boehmer, H.; Nabholz, M.

    1975-01-01

    Semiallogeneic radiation chimeras were prepared by injecting heavily irradiated F 1 hybrid mice with bone marrow cells from one parental strain; the bone marrow cells were treated with anti-theta serum and complement to remove T cells and injected in large numbers (2 x 10 7 cells). The mice survived in excellent health until sacrifice 6 mo later. Thoracic duct cannulation at this stage showed that the mice possessed normal numbers of recirculating lymphocytes. Close to 100 percent of thoracic duct lymphocytes and lymph node cells were shown to be of donor strain origin. The capacity of lymphocytes from the chimeras to respond to host-type determinants was tested in mixed leukocyte culture and in an assay for cell-mediated lympholysis (CML). Mixed leukocyte reactions (MLR) were measured both in vitro and in vivo; tumor cells and phytohemagglutinin-stimulated blast cells were used as target cells for measuring CML. While responding normally to third party determinants, cells from the chimeras gave a definite, though reduced MLR when exposed to host-type determinants. However, this proliferative response to host-type determinants, unlike that to third party determinants, was not associated with differentiation into cytotoxic lymphocytes

  1. Latent Microsporidiosis Caused by Encephalitozoon cuniculi in Immunocompetent Hosts: A Murine Model Demonstrating the Ineffectiveness of the Immune System and Treatment with Albendazole

    Science.gov (United States)

    Kotkova, Michaela; Sak, Bohumil; Kvetonova, Dana; Kvac, Martin

    2013-01-01

    Background Microsporidia are obligate intracellular parasites causing severe infections with lethal outcome in immunocompromised hosts. However, these pathogens are more frequently reported as latent infections in immunocompetent individuals and raises questions about the potential risk of reactivation following induced immunosuppression. Aims To evaluate the possibility latent microsporidiosis, efficacy or albendazole, and reactivation, the authors monitored the course of E. cuniculi infection in immunocompetent BALB/c mice and immunodeficient SCID mice using molecular methods. Methods Mice were per orally infected with 107 spores of E. cuniculi. Selected groups were treated with albendazole, re-infected or chemically immunosuppressed by dexamethasone. The presence of microsporidia in the host’s organs and feces were determined using PCR methods. Changes in numbers of lymphocytes in blood and in spleen after induction of immunosuppression were confirmed using flow cytometry analysis. Results Whereas E. cuniculi caused lethal microsporidiosis in SCID mice, the infection in BABL/c mice remained asymptomatic despite parasite dissemination into many organs during the acute infection phase. Albendazole treatment led to microsporidia elimination from organs in BALB/c mice. In SCID mice, however, only a temporary reduction in number of affected organs was observed and infection re-established post-treatment. Dexamethasone treatment resulted in a chronic microsporidia infection disseminating into most organs in BALB/c mice. Although the presence of E. cuniculi in organs of albendazole- treated mice was undetectable by PCR, it was striking that infection was reactivated by immunosuppression treatment. Conclusion Our results demonstrated that microsporidia can successfully survive in organs of immunocompetent hosts and are able to reactivate from undetectable levels and spread within these hosts after induction of immunosuppression. These findings stress the danger of

  2. Graft-versus-host reaction and immune function. III. Functional pre-T cells in the bone marrow of graft-versus-host-reactive mice displaying T cell immunodeficiency

    International Nuclear Information System (INIS)

    Seddik, M.; Seemayer, T.A.; Lapp, W.S.

    1986-01-01

    Studies were performed to determine whether pre-T cells develop normally in the bone marrow of mice displaying thymic dysplasia and T cell immunodeficiency as a consequence of a graft-versus-host (GVH) reaction. GVH reactions were induced in CBAxAF1 mice by the injection of A strain lymphoid cells. To test for the presence of pre-T cells in GVH-reactive mice, bone marrow from GVH-reactive mice (GVHBM) was injected into irradiated syngeneic F1 mice and 30-40 days later thymic morphology and function were studied. Morphology studies showed nearly normal thymic architectural restoration; moreover, such glands contained normal numbers of Thy-1-positive cells. Functional pre-T cells were evaluated by transferring thymocytes from the irradiated GVHBM-reconstituted mice into T-cell-deprived mice. These thymocytes reconstituted allograft reactivity, T helper cell function and Con A and PHA mitogen responses of T-cell-deprived mice. These results suggest that the pre-T cell population in the bone marrow is not affected by the GVH reaction. Therefore, the T cell immunodeficiency associated with the GVH reaction is not due to a deficiency of pre-T cells in the bone marrow but is more likely associated with GVH-induced thymic dysplasia

  3. Genome-wide characterization of Toll-like receptor gene family in common carp (Cyprinus carpio) and their involvement in host immune response to Aeromonas hydrophila infection.

    Science.gov (United States)

    Gong, Yiwen; Feng, Shuaisheng; Li, Shangqi; Zhang, Yan; Zhao, Zixia; Hu, Mou; Xu, Peng; Jiang, Yanliang

    2017-12-01

    The Toll-like receptor (TLR) gene family is a class of conserved pattern recognition receptors, which play an essential role in innate immunity providing efficient defense against invading microbial pathogens. Although TLRs have been extensively characterized in both invertebrates and vertebrates, a comprehensive analysis of TLRs in common carp is lacking. In the present study, we have conducted the first genome-wide systematic analysis of common carp (Cyprinus carpio) TLR genes. A set of 27 common carp TLR genes were identified and characterized. Sequence similarity analysis, functional domain prediction and phylogenetic analysis supported their annotation and orthologies. By examining the gene copy number of TLR genes across several vertebrates, gene duplications and losses were observed. The expression patterns of TLR genes were examined during early developmental stages and in various healthy tissues, and the results showed that TLR genes were ubiquitously expressed, indicating a likely role in maintaining homeostasis. Moreover, the differential expression of TLRs was examined after Aeromons hydrophila infection, and showed that most TLR genes were induced, with diverse patterns. TLR1, TLR4-2, TLR4-3, TLR22-2, TLR22-3 were significantly up-regulated at minimum one timepoint, whereas TLR2-1, TLR4-1, TLR7-1 and TLR7-2 were significantly down-regulated. Our results suggested that TLR genes play critical roles in the common carp immune response. Collectively, our findings provide fundamental genomic resources for future studies on fish disease management and disease-resistance selective breeding strategy development. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Influence of early enteral nutrition on nutritional status, immunity and body composition in postoperative elderly gastric cancer patients%早期肠内营养对老年胃癌术后患者营养免疫及人体成分的影响

    Institute of Scientific and Technical Information of China (English)

    王凤; 王庆华; 陈强谱

    2011-01-01

    目的 探讨早期肠内营养(EEN)对老年胃癌患者术后营养、免疫和人体成分的影响.方法 将360例老年胃癌患者分为EEN组和肠外营养(PN)组各180例.EEN组术后20~24 h开始行EEN;PN组术后1d经周围静脉或中心静脉开始PN.术前、术后1d、7d检测营养指标、免疫和人体成分指标测量.结果 两组患者术后营养、免疫指标及人体成分指标值均有降低,但EEN组术后下降程度显著小于PN组(均P<0.05),并发症发生率低于PN组.结论 老年胃癌患者术后EEN支持能有效改善营养状况、免疫功能和人体成分的变化,减少术后并发症的发生,有利于促进患者康复.%Objective To study the effect of early enteral nutrition on nutritional status, immunity and body composition in elderly patients with gastric cancer after operations. Methods A total of 360 patients with gastric cancer after operation were equally randomized into two groups receiving either parenteral nutrition (PN group) on the first postoperative day or early enteral nutrition (EN group) in 20-hour to 24-hour postoperative period. The parameters of nutritional status, immunity and body composition were measured before operation and on the first and seventh postoperative days. Results The values of parameters of nutritional status, immunity and body composition decreased after operation in both groups, with the fluctuations of parameters in the EN group being smaller than the PN group (P<0. 05 for all). The incidence of complications in the EN group was lower than the PN group. Conclusion Early enteral nutrition can improve nutritional status, immune function and body composition in elderly patients with gastric cancer after operations, reduce complications, and promote patients recovery.

  5. Inheritance of the lysozyme inhibitor Ivy was an important evolutionary step by Yersinia pestis to avoid the host innate immune response.

    Science.gov (United States)

    Derbise, Anne; Pierre, François; Merchez, Maud; Pradel, Elizabeth; Laouami, Sabrina; Ricard, Isabelle; Sirard, Jean-Claude; Fritz, Jill; Lemaître, Nadine; Akinbi, Henry; Boneca, Ivo G; Sebbane, Florent

    2013-05-15

    Yersinia pestis (the plague bacillus) and its ancestor, Yersinia pseudotuberculosis (which causes self-limited bowel disease), encode putative homologues of the periplasmic lysozyme inhibitor Ivy and the membrane-bound lysozyme inhibitor MliC. The involvement of both inhibitors in virulence remains subject to debate. Mutants lacking ivy and/or mliC were generated. We evaluated the mutants' ability to counter lysozyme, grow in serum, and/or counter leukocytes; to produce disease in wild-type, neutropenic, or lysozyme-deficient rodents; and to induce host inflammation. MliC was not required for lysozyme resistance and the development of plague. Deletion of ivy decreased Y. pestis' ability to counter lysozyme and polymorphonuclear neutrophils, but it did not affect the bacterium's ability to grow in serum or resist macrophages. Y. pestis lacking Ivy had attenuated virulence, unless animals were neutropenic or lysozyme deficient. The Ivy mutant induced inflammation to a degree similar to that of the parental strain. Last, Y. pseudotuberculosis did not require Ivy to counter lysozyme and for virulence. Ivy is required to counter lysozyme during infection, but its role as a virulence factor is species dependent. Our study also shows that a gene that is not necessary for the virulence of an ancestral bacterium may become essential in the emergence of a new pathogen.

  6. Understanding postoperative fatigue.

    Science.gov (United States)

    Rose, E A; King, T C

    1978-07-01

    Performance characteristics of the central nervous, cardiovascular, respiratory and muscular systems in man postoperatively have received little investigative attention, despite the well known syndrome of postoperative fatigue. The impairmen in perception and psychomotor skills that has been shown to result from caloric restriction, bedrest, sedation and sleep deprivation suggests that a similar deficit may occur after surgical procedures. After a simple elective surgical procedure, maximal oxygen uptake decreases and the adaptability of heart rate to submaximal workloads is impaired. Similar deleterious effects on cardiorespiratory performance have been documented with starvation and bedrest; an understanding of cardiorespiratory performance postoperatively awaits further investigation. Maximal muscular force of contraction is also impaired by caloric restriction and bedrest, suggesting that similar effects may be seen in the postoperative state, although this has not been studied. A better understanding of the syndrome of postoperative fatigue could be achieved by a descriptive analysis of physiologic performance postoperatively. Such descriptive data could form the basis for objective evaluation of therapeutic measures intended to improve performance, such as nutritional supplementation and pharmacologic intervention. The observation that exercise with the patient in the supine position may decrease the impairment in maximal aerobic power otherwise expected in immobilized patients suggests that controlled exercise therapy may be of value in reducing physiologic impairment postoperatively.

  7. Identification and molecular profiling of DC-SIGN-like from big belly seahorse (Hippocampus abdominalis) inferring its potential relevancy in host immunity.

    Science.gov (United States)

    Jo, Eunyoung; Elvitigala, Don Anushka Sandaruwan; Wan, Qiang; Oh, Minyoung; Oh, Chulhong; Lee, Jehee

    2017-12-01

    Dendritic-cell-specific ICAM-3-grabbing non-integrin (DC-SIGN) is a C-type lectin that functions as a pattern recognition receptor by recognizing pathogen-associated molecular patterns (PAMPs). It is also involved in various events of the dendritic cell (DC) life cycle, such as DC migration, antigen capture and presentation, and T cell priming. In this study, a DC-SIGN-like gene from the big belly seahorse Hippocampus abdominalis (designated as ShDCS-like) was identified and molecularly characterized. The putative, complete ORF was found to be 1368 bp in length, encoding a protein of 462 amino acids with a molecular mass of 52.6 kDa and a theoretical isoelectric point of 8.26. The deduced amino acid sequence contains a single carbohydrate recognition domain (CRD), in which six conserved cysteine residues and two Ca 2+ -binding site motifs (QPN, WND) were identified. Based on pairwise sequence analysis, ShDCS-like exhibits the highest amino acid identity (94.6%) and similarity (97.4%) with DC-SIGN-like counterpart from tiger tail seahorse Hippocampus comes. Quantitative real-time PCR revealed that ShDCS-like mRNA is transcribed universally in all tissues examined, but with abundance in kidney and gill tissues. The basal mRNA expression of ShDCS-like was modulated in blood cell, kidney, gill and liver tissues in response to the stimulation of healthy fish with lipopolysaccharides (LPS), Edwardsiella tarda, or Streptococcus iniae. Moreover, recombinant ShDCS-like-CRD domain exhibited detectable agglutination activity against different bacteria. Collectively, these results suggest that ShDCS-like may potentially involve in immune function in big belly seahorses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. The Drosophila melanogaster host model

    Science.gov (United States)

    Igboin, Christina O.; Griffen, Ann L.; Leys, Eugene J.

    2012-01-01

    The deleterious and sometimes fatal outcomes of bacterial infectious diseases are the net result of the interactions between the pathogen and the host, and the genetically tractable fruit fly, Drosophila melanogaster, has emerged as a valuable tool for modeling the pathogen–host interactions of a wide variety of bacteria. These studies have revealed that there is a remarkable conservation of bacterial pathogenesis and host defence mechanisms between higher host organisms and Drosophila. This review presents an in-depth discussion of the Drosophila immune response, the Drosophila killing model, and the use of the model to examine bacterial–host interactions. The recent introduction of the Drosophila model into the oral microbiology field is discussed, specifically the use of the model to examine Porphyromonas gingivalis–host interactions, and finally the potential uses of this powerful model system to further elucidate oral bacterial-host interactions are addressed. PMID:22368770

  9. The Drosophila melanogaster host model

    Directory of Open Access Journals (Sweden)

    Christina O. Igboin

    2012-02-01

    Full Text Available The deleterious and sometimes fatal outcomes of bacterial infectious diseases are the net result of the interactions between the pathogen and the host, and the genetically tractable fruit fly, Drosophila melanogaster, has emerged as a valuable tool for modeling the pathogen–host interactions of a wide variety of bacteria. These studies have revealed that there is a remarkable conservation of bacterial pathogenesis and host defence mechanisms between higher host organisms and Drosophila. This review presents an in-depth discussion of the Drosophila immune response, the Drosophila killing model, and the use of the model to examine bacterial–host interactions. The recent introduction of the Drosophila model into the oral microbiology field is discussed, specifically the use of the model to examine Porphyromonas gingivalis–host interactions, and finally the potential uses of this powerful model system to further elucidate oral bacterial-host interactions are addressed.

  10. The Drosophila melanogaster host model.

    Science.gov (United States)

    Igboin, Christina O; Griffen, Ann L; Leys, Eugene J

    2012-01-01

    The deleterious and sometimes fatal outcomes of bacterial infectious diseases are the net result of the interactions between the pathogen and the host, and the genetically tractable fruit fly, Drosophila melanogaster, has emerged as a valuable tool for modeling the pathogen-host interactions of a wide variety of bacteria. These studies have revealed that there is a remarkable conservation of bacterial pathogenesis and host defence mechanisms between higher host organisms and Drosophila. This review presents an in-depth discussion of the Drosophila immune response, the Drosophila killing model, and the use of the model to examine bacterial-host interactions. The recent introduction of the Drosophila model into the oral microbiology field is discussed, specifically the use of the model to examine Porphyromonas gingivalis-host interactions, and finally the potential uses of this powerful model system to further elucidate oral bacterial-host interactions are addressed.

  11. [Characteristics of postoperative peritonitis].

    Science.gov (United States)

    Lock, J F; Eckmann, C; Germer, C-T

    2016-01-01

    Postoperative peritonitis is still a life-threatening complication after abdominal surgery and approximately 10,000 patients annually develop postoperative peritonitis in Germany. Early recognition and diagnosis before the onset of sepsis has remained a clinical challenge as no single specific screening test is available. The aim of therapy is a rapid and effective control of the source of infection and antimicrobial therapy. After diagnosis of diffuse postoperative peritonitis surgical revision is usually inevitable after intestinal interventions. Peritonitis after liver, biliary or pancreatic surgery is managed as a rule by means of differentiated therapy approaches depending on the severity.

  12. Host Factors in Ebola Infection.

    Science.gov (United States)

    Rasmussen, Angela L

    2016-08-31

    Ebola virus (EBOV) emerged in West Africa in 2014 to devastating effect, and demonstrated that infection can cause a broad range of severe disease manifestations. As the virus itself was genetically similar to other Zaire ebolaviruses, the spectrum of pathology likely resulted from variable responses to infection in a large and genetically diverse population. This review comprehensively summarizes current knowledge of the host response to EBOV infection, including pathways hijacked by the virus to facilitate replication, host processes that contribute directly to pathogenesis, and host-pathogen interactions involved in subverting or antagonizing host antiviral immunity.

  13. The postoperative stomach

    Energy Technology Data Exchange (ETDEWEB)

    Woodfield, Courtney A. [Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104 (United States); Levine, Marc S. [Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104 (United States)]. E-mail: marc.levine@uphs.upenn.edu

    2005-03-01

    Gastric surgery may be performed for the treatment of a variety of benign and malignant diseases of the upper gastrointestinal tract, including peptic ulcers and gastric carcinoma. Radiographic studies with water-soluble contrast agents often are obtained to rule out leaks, obstruction, or other acute complications during the early postoperative period. Barium studies may also be obtained to evaluate for anastomotic strictures or ulcers, bile reflux gastritis, recurrent tumor, or other chronic complications during the late postoperative period. Cross-sectional imaging studies such as CT are also helpful for detecting abscesses or other postoperative collections, recurrent or metastatic tumor, or less common complications such as afferent loop syndrome or gastrojejunal intussusception. It is important for radiologists to be familiar not only with the radiographic findings associated with these various abnormalities but also with the normal appearances of the postoperative stomach on radiographic examinations, so that such appearances are not mistaken for pseudoleaks or other postoperative complications. The purpose of this article is to describe the normal postsurgical anatomy after the most commonly performed operations (including partial gastrectomy, esophagogastrectomy and gastric pull-through, and total gastrectomy and esophagojejunostomy) and to review the acute and chronic complications, normal postoperative findings, and major abnormalities detected on radiographic examinations in these patients.

  14. The postoperative stomach

    International Nuclear Information System (INIS)

    Woodfield, Courtney A.; Levine, Marc S.

    2005-01-01

    Gastric surgery may be performed for the treatment of a variety of benign and malignant diseases of the upper gastrointestinal tract, including peptic ulcers and gastric carcinoma. Radiographic studies with water-soluble contrast agents often are obtained to rule out leaks, obstruction, or other acute complications during the early postoperative period. Barium studies may also be obtained to evaluate for anastomotic strictures or ulcers, bile reflux gastritis, recurrent tumor, or other chronic complications during the late postoperative period. Cross-sectional imaging studies such as CT are also helpful for detecting abscesses or other postoperative collections, recurrent or metastatic tumor, or less common complications such as afferent loop syndrome or gastrojejunal intussusception. It is important for radiologists to be familiar not only with the radiographic findings associated with these various abnormalities but also with the normal appearances of the postoperative stomach on radiographic examinations, so that such appearances are not mistaken for pseudoleaks or other postoperative complications. The purpose of this article is to describe the normal postsurgical anatomy after the most commonly performed operations (including partial gastrectomy, esophagogastrectomy and gastric pull-through, and total gastrectomy and esophagojejunostomy) and to review the acute and chronic complications, normal postoperative findings, and major abnormalities detected on radiographic examinations in these patients

  15. Kidney and innate immunity.

    Science.gov (United States)

    Wang, Ying-Hui; Zhang, Yu-Gen

    2017-03-01

    Innate immune system is an important modulator of the inflammatory response during infection and tissue injury/repair. The kidney as a vital organ with high energy demand plays a key role in regulating the disease related metabolic process. Increasing research interest has focused on the immune pathogenesis of many kidney diseases. However, innate immune cells such as dendritic cells, macrophages, NK cells and a few innate lymphocytes, as well as the complement system are essential for renal immune homeostasis and ensure a coordinated balance between tissue injury and regeneration. The innate immune response provides the first line of host defense initiated by several classes of pattern recognition receptors (PRRs), such as membrane-bound Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), together with inflammasomes responsible for early innate immune response. Although the innate immune system is well studied, the research on the detailed relationship between innate immunity and kidney is still very limited. In this review, we will focus on the innate immune sensing system in renal immune homeostasis, as well as the corresponding pathogenesis of many kidney diseases. The pivotal roles of innate immunity in renal injury and regeneration with special emphasis on kidney disease related immunoregulatory mechanism are also discussed. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  16. Mechanisms regulating skin immunity and inflammation.

    Science.gov (United States)

    Pasparakis, Manolis; Haase, Ingo; Nestle, Frank O

    2014-05-01

    Immune responses in the skin are important for host defence against pathogenic microorganisms. However, dysregulated immune reactions can cause chronic inflammatory skin diseases. Extensive crosstalk between the different cellular and microbial components of the skin regulates local immune responses to ensure efficient host defence, to maintain and restore homeostasis, and to prevent chronic disease. In this Review, we discuss recent findings that highlight the complex regulatory networks that control skin immunity, and we provide new paradigms for the mechanisms that regulate skin immune responses in host defence and in chronic inflammation.

  17. Immunity to Fish Rhabdoviruses

    OpenAIRE

    Purcell, Maureen K.; Laing, Kerry J.; Winton, James R.

    2012-01-01

    Members of the family Rhabdoviridae are single-stranded RNA viruses and globally important pathogens of wild and cultured fish and thus relatively well studied in their respective hosts or other model systems. Here, we review the protective immune mechanisms that fish mount in response to rhabdovirus infections. Teleost fish possess the principal components of innate and adaptive immunity found in other vertebrates. Neutralizing antibodies are critical for long-term protection from fish rhabd...

  18. Postoperative spine infections

    Directory of Open Access Journals (Sweden)

    Paolo Domenico Parchi

    2015-09-01

    Full Text Available Postoperative spinal wound infection is a potentially devastating complication after operative spinal procedures. Despite the utilization of perioperative prophylactic antibiotics in recent years and improvements in surgical technique and postoperative care, wound infection continues to compromise patients’ outcome after spinal surgery. In the modern era of pending health care reform with increasing financial constraints, the financial burden of post-operative spinal infections also deserves consideration. The aim of our work is to give to the reader an updated review of the latest achievements in prevention, risk factors, diagnosis, microbiology and treatment of post-operative spinal wound infections. A review of the scientific literature was carried out using electronic medical databases Pubmed, Google Scholar, Web of Science and Scopus for the years 1973-2012 to obtain access to all publications involving the incidence, risk factors, prevention, diagnosis, treatment of postoperative spinal wound infections. We initially identified 119 studies; of these 60 were selected. Despite all the measures intended to reduce the incidence of surgical site infections in spine surgery, these remain a common and potentially dangerous complication.

  19. Mammalian Gut Immunity

    Science.gov (United States)

    Chassaing, Benoit; Kumar, Manish; Baker, Mark T.; Singh, Vishal; Vijay-Kumar, Matam

    2016-01-01

    The mammalian intestinal tract is the largest immune organ in the body and comprises cells from non-hemopoietic (epithelia, Paneth cells, goblet cells) and hemopoietic (macrophages, dendritic cells, T-cells) origin, and is also a dwelling for trillions of microbes collectively known as the microbiota. The homeostasis of this large microbial biomass is prerequisite to maintain host health by maximizing beneficial symbiotic relationships and minimizing the risks of living in such close proximity. Both microbiota and host immune system communicate with each other to mutually maintain homeostasis in what could be called a “love–hate relationship.” Further, the host innate and adaptive immune arms of the immune system cooperate and compensate each other to maintain the equilibrium of a highly complex gut ecosystem in a stable and stringent fashion. Any imbalance due to innate or adaptive immune deficiency or aberrant immune response may lead to dysbiosis and low-grade to robust gut inflammation, finally resulting in metabolic diseases. PMID:25163502

  20. [Postoperative cognitive deficits].

    Science.gov (United States)

    Kalezić, Nevena; Dimitrijević, Ivan; Leposavić, Ljubica; Kocica, Mladen; Bumbasirević, Vesna; Vucetić, Cedomir; Paunović, Ivan; Slavković, Nemanja; Filimonović, Jelena

    2006-01-01

    Cognitive dysfunctions are relatively common in postoperative and critically ill patients. This complication not only compromises recovery after surgery, but, if persistent, it minimizes and compromises surgery itself. Risk factors of postoperative cognitive disorders can be divided into age and comorbidity dependent, and those related to anesthesia and surgery. Cardiovascular, orthopedic and urologic surgery carries high risk of postoperative cognitive dysfunction. It can also occur in other types of surgical treatment, especially in elderly. Among risk factors of cognitive disorders, associated with comorbidity, underlying psychiatric and neurological disorders, substance abuse and conditions with elevation of intracranial pressure are in the first place in postoperative patients. Preoperative and perioperative predisposing conditions for cognitive dysfunction and their incidence were described in our paper. These are: geriatric patients, patients with substance abuse, preexisting psychiatric or cognitive disorders, neurologic disease with high intracranial pressure, cerebrovascular insufficiency, epilepsia, preeclampsia, acute intermittent porphyria, operation type, brain hypoxia, changes in blood glucose level, electrolyte imbalance, anesthetic agents, adjuvant medication and intraoperative awareness. For each of these factors, evaluation, prevention and treatment strategies were suggested, with special regard on anesthetic technique.

  1. Postoperative Chemotherapy for Medulloblastoma

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2005-03-01

    Full Text Available The survival rate and cognitive function of 43 children, age <3 years, with medulloblastoma treated with intensive postoperative chemotherapy alone, without radiotherapy, were determined at the University of Wurzburg and other centers in Germany Chemotherapy consisted of three two-month cycles of cyclophosphamide, methotrexate, vincristine, carboplatin, and etoposide.

  2. Management of Postoperative Respiratory Failure.

    Science.gov (United States)

    Mulligan, Michael S; Berfield, Kathleen S; Abbaszadeh, Ryan V

    2015-11-01

    Despite best efforts, postoperative complications such as postoperative respiratory failure may occur and prompt recognition of the process and management is required. Postoperative respiratory failure, such as postoperative pneumonia, postpneumonectomy pulmonary edema, acute respiratory distress-like syndromes, and pulmonary embolism, are associated with high morbidity and mortality. The causes of these complications are multifactorial and depend on preoperative, intraoperative, and postoperative factors, some of which are modifiable. The article identifies some of the risk factors, causes, and treatment strategies for successful management of the patient with postoperative respiratory failure. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Self-consuming innate immunity in Arabidopsis

    DEFF Research Database (Denmark)

    Hofius, Daniel; Mundy, John; Petersen, Morten

    2009-01-01

    Programmed cell death (PCD) associated with the pathogen-induced hypersensitive response (HR) is a hallmark of plant innate immunity. HR PCD is triggered upon recognition of pathogen effector molecules by host immune receptors either directly or indirectly via effector modulation of host targets...

  4. Pediatric cardiac postoperative care

    Directory of Open Access Journals (Sweden)

    Auler Jr. José Otávio Costa

    2002-01-01

    Full Text Available The Heart Institute of the University of São Paulo, Medical School is a referral center for the treatment of congenital heart diseases of neonates and infants. In the recent years, the excellent surgical results obtained in our institution may be in part due to modern anesthetic care and to postoperative care based on well-structured protocols. The purpose of this article is to review unique aspects of neonate cardiovascular physiology, the impact of extracorporeal circulation on postoperative evolution, and the prescription for pharmacological support of acute cardiac dysfunction based on our cardiac unit protocols. The main causes of low cardiac output after surgical correction of heart congenital disease are reviewed, and methods of treatment and support are proposed as derived from the relevant literature and our protocols.

  5. Spreading of multiple epidemics with cross immunization.

    Science.gov (United States)

    Uekermann, Florian; Sneppen, Kim

    2012-09-01

    Pathogen-host relationships are the result of an ongoing coevolutionary race where the immune system of the host attempts to eliminate the pathogen, while the successful pathogen mutates to become invisible for the host's immune system. We here propose a minimal pathogen-host evolution model that takes into account cross immunization and allows for evolution of a spatially heterogeneous immune status of a population of hosts. With only the mutation rate as a determining parameter, the model allows us to produce an evolutionary tree of diseases which is highly branched, but hardly ever splits into separate long-lived trunks. Side branches remain short lived and seldom diverge to the extent of losing all cross immunizations.

  6. Immunity: Insect Immune Memory Goes Viral.

    Science.gov (United States)

    Ligoxygakis, Petros

    2017-11-20

    Adaptive memory in insect immunity has been controversial. In this issue, Andino and co-workers propose that acquisition of viral sequences in the host genome gives rise to anti-sense, anti-viral piRNAs. Such sequences can be regarded as both a genomic archive of past infections and as an armour of potential heritable memory. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Immune System Toxicity and Immunotoxicity Hazard Identification

    Science.gov (United States)

    Exposure to chemicals may alter immune system health, increasing the risk of infections, allergy and autoimmune diseases. The chapter provides a concise overview of the immune system, host factors that affect immune system heal, and the effects that xenobiotic exposure may have ...

  8. Biofilms and host response - helpful or harmful

    DEFF Research Database (Denmark)

    Moser, Claus; Pedersen, Hannah Trøstrup; Lerche, Christian Johann

    2017-01-01

    infections can present in numerous ways, one common feature is involvement of the host response with significant impact on the course. A special characteristic is the synergy of the innate and the acquired immune responses for the induced pathology. Here, we review the impact of the host response...

  9. Immune regulation by microbiome metabolites.

    Science.gov (United States)

    Kim, Chang H

    2018-03-22

    Commensal microbes and the host immune system have been co-evolved for mutual regulation. Microbes regulate the host immune system, in part, by producing metabolites. A mounting body of evidence indicates that diverse microbial metabolites profoundly regulate the immune system via host receptors and other target molecules. Immune cells express metabolite-specific receptors such as P2X 7 , GPR41, GPR43, GPR109A, aryl hydrocarbon receptor precursor (AhR), pregnane X receptor (PXR), farnesoid X receptor (FXR), TGR5 and other molecular targets. Microbial metabolites and their receptors form an extensive array of signals to respond to changes in nutrition, health and immunological status. As a consequence, microbial metabolite signals contribute to nutrient harvest from diet, and regulate host metabolism and the immune system. Importantly, microbial metabolites bidirectionally function to promote both tolerance and immunity to effectively fight infection without developing inflammatory diseases. In pathogenic conditions, adverse effects of microbial metabolites have been observed as well. Key immune-regulatory functions of the metabolites, generated from carbohydrates, proteins and bile acids, are reviewed in this article. © 2018 John Wiley & Sons Ltd.

  10. Host-to-host variation of ecological interactions in polymicrobial infections

    Science.gov (United States)

    Mukherjee, Sayak; Weimer, Kristin E.; Seok, Sang-Cheol; Ray, Will C.; Jayaprakash, C.; Vieland, Veronica J.; Swords, W. Edward; Das, Jayajit

    2015-02-01

    Host-to-host variability with respect to interactions between microorganisms and multicellular hosts are commonly observed in infection and in homeostasis. However, the majority of mechanistic models used to analyze host-microorganism relationships, as well as most of the ecological theories proposed to explain coevolution of hosts and microbes, are based on averages across a host population. By assuming that observed variations are random and independent, these models overlook the role of differences between hosts. Here, we analyze mechanisms underlying host-to-host variations of bacterial infection kinetics, using the well characterized experimental infection model of polymicrobial otitis media (OM) in chinchillas, in combination with population dynamic models and a maximum entropy (MaxEnt) based inference scheme. We find that the nature of the interactions between bacterial species critically regulates host-to-host variations in these interactions. Surprisingly, seemingly unrelated phenomena, such as the efficiency of individual bacterial species in utilizing nutrients for growth, and the microbe-specific host immune response, can become interdependent in a host population. The latter finding suggests a potential mechanism that could lead to selection of specific strains of bacterial species during the coevolution of the host immune response and the bacterial species.

  11. Host-to-host variation of ecological interactions in polymicrobial infections.

    Science.gov (United States)

    Mukherjee, Sayak; Weimer, Kristin E; Seok, Sang-Cheol; Ray, Will C; Jayaprakash, C; Vieland, Veronica J; Swords, W Edward; Das, Jayajit

    2014-12-04

    Host-to-host variability with respect to interactions between microorganisms and multicellular hosts are commonly observed in infection and in homeostasis. However, the majority of mechanistic models used to analyze host-microorganism relationships, as well as most of the ecological theories proposed to explain coevolution of hosts and microbes, are based on averages across a host population. By assuming that observed variations are random and independent, these models overlook the role of differences between hosts. Here, we analyze mechanisms underlying host-to-host variations of bacterial infection kinetics, using the well characterized experimental infection model of polymicrobial otitis media (OM) in chinchillas, in combination with population dynamic models and a maximum entropy (MaxEnt) based inference scheme. We find that the nature of the interactions between bacterial species critically regulates host-to-host variations in these interactions. Surprisingly, seemingly unrelated phenomena, such as the efficiency of individual bacterial species in utilizing nutrients for growth, and the microbe-specific host immune response, can become interdependent in a host population. The latter finding suggests a potential mechanism that could lead to selection of specific strains of bacterial species during the coevolution of the host immune response and the bacterial species.

  12. Immune responses to metastases

    International Nuclear Information System (INIS)

    Herberman, R.B.; Wiltrout, R.H.; Gorelik, E.

    1987-01-01

    The authors present the changes in the immune system in tumor-bearing hosts that may influence the development of progression of metastases. Included are mononuclear cell infiltration of metastases; alterations in natural resistance mediated by natural killer cells and macrophages; development of specific immunity mediated by T-lymphocytes or antibodies; modulation of tumor-associated antigen expression; and the down-regulation of the immune response to the tumor by several suppressor mechanisms; the augmentation of the immune response and its potential for therapeutic application; includes the prophylaxis of metastases formation by NK cells; the therapy of metastases by augmentation NK-, macrophage-, or T-lymphocyte-mediated responses by biological response modifiers; and the transfer of anticancer activity by cytoxic T-lymphocytes or immunoconjugates of monoclonal antibodies with specificity for tumors

  13. Postoperative care in geriatrics

    Directory of Open Access Journals (Sweden)

    Grzegorz Ulenberg

    2017-08-01

    Full Text Available Treatment of the elderly is becoming increasingly common problem and is of interest, because in the future this phenomenon will affect most of us. For many years, he observed in different countries increasingly rapid aging of the population, including in Poland. The operation in such a patient poses a high risk of complications and life-threatening conditions. Their age makes in the postoperative period there are many medical problems. Many factors can affect the scope of a different self-care nursing with such a patient.

  14. Postoperative conversion disorder.

    Science.gov (United States)

    Afolabi, Kola; Ali, Sameer; Gahtan, Vivian; Gorji, Reza; Li, Fenghua; Nussmeier, Nancy A

    2016-05-01

    Conversion disorder is a psychiatric disorder in which psychological stress causes neurologic deficits. A 28-year-old female surgical patient had uneventful general anesthesia and emergence but developed conversion disorder 1 hour postoperatively. She reported difficulty speaking, right-hand numbness and weakness, and right-leg paralysis. Neurologic examination and imaging revealed no neuronal damage, herniation, hemorrhage, or stroke. The patient mentioned failing examinations the day before surgery and discontinuing her prescribed antidepressant medication, leading us to diagnose conversion disorder, with eventual confirmation by neuroimaging and follow-up examinations. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. CNS tumors: postoperative evaluation

    International Nuclear Information System (INIS)

    Dayanir, Y.

    2012-01-01

    Full text: Imaging assessment of brain tumors following surgery is complex and depends upon several factors, including the location of the tumor, the surgical procedure and the disease process for which it was performed. Depending upon these factors, one or a combination of complementary imaging modalities may be required to demonstrate any clinically relevant situation, to assist the surgeon in deciding if repeat surgery is necessary. Conventional magnetic resonance imaging (MRI) can show the shape, size, signal intensity, and enhancement of a brain tumor. It has been widely used to diagnose and differentiate brain tumors and to assess the surgery outcomes. Longitudinal MRI scans have also been applied for the assessment of treatment and response to surgery. The newly developed MRI techniques, including diffusion weighted imaging (DWI), perfusion weighted imaging (PWI) and magnetic resonance spectroscopy (MRS), have the potential to provide the molecular, functional and metabolic information of preoperative and postoperative brain tumors. Postoperative diffusion and perfusion magnetic resonance imaging are especially useful in predicting early functional recovery from new deficits after brain tumor surgery.This lecture will stress the principles, applications, and pitfalls of conventional as well as newly developing functional imaging techniques following operation of brain tumors

  16. Immune Evasion, Immunopathology and the Regulation of the Immune System

    Directory of Open Access Journals (Sweden)

    Bruno Faivre

    2013-02-01

    Full Text Available Costs and benefits of the immune response have attracted considerable attention in the last years among evolutionary biologists. Given the cost of parasitism, natural selection should favor individuals with the most effective immune defenses. Nevertheless, there exists huge variation in the expression of immune effectors among individuals. To explain this apparent paradox, it has been suggested that an over-reactive immune system might be too costly, both in terms of metabolic resources and risks of immune-mediated diseases, setting a limit to the investment into immune defenses. Here, we argue that this view neglects one important aspect of the interaction: the role played by evolving pathogens. We suggest that taking into account the co-evolutionary interactions between the host immune system and the parasitic strategies to overcome the immune response might provide a better picture of the selective pressures that shape the evolution of immune functioning. Integrating parasitic strategies of host exploitation can also contribute to understand the seemingly contradictory results that infection can enhance, but also protect from, autoimmune diseases. In the last decades, the incidence of autoimmune disorders has dramatically increased in wealthy countries of the northern hemisphere with a concomitant decrease of most parasitic infections. Experimental work on model organisms has shown that this pattern may be due to the protective role of certain parasites (i.e., helminths that rely on the immunosuppression of hosts for their persistence. Interestingly, although parasite-induced immunosuppression can protect against autoimmunity, it can obviously favor the spread of other infections. Therefore, we need to think about the evolution of the immune system using a multidimensional trade-off involving immunoprotection, immunopathology and the parasitic strategies to escape the immune response.

  17. Filoviral Immune Evasion Mechanisms

    Directory of Open Access Journals (Sweden)

    Christopher F. Basler

    2011-09-01

    Full Text Available The Filoviridae family of viruses, which includes the genera Ebolavirus (EBOV and Marburgvirus (MARV, causes severe and often times lethal hemorrhagic fever in humans. Filoviral infections are associated with ineffective innate antiviral responses as a result of virally encoded immune antagonists, which render the host incapable of mounting effective innate or adaptive immune responses. The Type I interferon (IFN response is critical for establishing an antiviral state in the host cell and subsequent activation of the adaptive immune responses. Several filoviral encoded components target Type I IFN responses, and this innate immune suppression is important for viral replication and pathogenesis. For example, EBOV VP35 inhibits the phosphorylation of IRF-3/7 by the TBK-1/IKKε kinases in addition to sequestering viral RNA from detection by RIG-I like receptors. MARV VP40 inhibits STAT1/2 phosphorylation by inhibiting the JAK family kinases. EBOV VP24 inhibits nuclear translocation of activated STAT1 by karyopherin-α. The examples also represent distinct mechanisms utilized by filoviral proteins in order to counter immune responses, which results in limited IFN-α/β production and downstream signaling.

  18. Immunity to fish rhabdoviruses

    Science.gov (United States)

    Purcell, Maureen K.; Laing, Kerry J.; Winton, James R.

    2012-01-01

    Members of the family Rhabdoviridae are single-stranded RNA viruses and globally important pathogens of wild and cultured fish and thus relatively well studied in their respective hosts or other model systems. Here, we review the protective immune mechanisms that fish mount in response to rhabdovirus infections. Teleost fish possess the principal components of innate and adaptive immunity found in other vertebrates. Neutralizing antibodies are critical for long-term protection from fish rhabdoviruses, but several studies also indicate a role for cell-mediated immunity. Survival of acute rhabdoviral infection is also dependent on innate immunity, particularly the interferon (IFN) system that is rapidly induced in response to infection. Paradoxically, rhabdoviruses are sensitive to the effects of IFN but virulent rhabdoviruses can continue to replicate owing to the abilities of the matrix (M) protein to mediate host-cell shutoff and the non-virion (NV) protein to subvert programmed cell death and suppress functional IFN. While many basic features of the fish immune response to rhabdovirus infections are becoming better understood, much less is known about how factors in the environment affect the ecology of rhabdovirus infections in natural populations of aquatic animals.

  19. Immunity to fish rhabdoviruses.

    Science.gov (United States)

    Purcell, Maureen K; Laing, Kerry J; Winton, James R

    2012-01-01

    Members of the family Rhabdoviridae are single-stranded RNA viruses and globally important pathogens of wild and cultured fish and thus relatively well studied in their respective hosts or other model systems. Here, we review the protective immune mechanisms that fish mount in response to rhabdovirus infections. Teleost fish possess the principal components of innate and adaptive immunity found in other vertebrates. Neutralizing antibodies are critical for long-term protection from fish rhabdoviruses, but several studies also indicate a role for cell-mediated immunity. Survival of acute rhabdoviral infection is also dependent on innate immunity, particularly the interferon (IFN) system that is rapidly induced in response to infection. Paradoxically, rhabdoviruses are sensitive to the effects of IFN but virulent rhabdoviruses can continue to replicate owing to the abilities of the matrix (M) protein to mediate host-cell shutoff and the non‑virion (NV) protein to subvert programmed cell death and suppress functional IFN. While many basic features of the fish immune response to rhabdovirus infections are becoming better understood, much less is known about how factors in the environment affect the ecology of rhabdovirus infections in natural populations of aquatic animals.

  20. Immunity to Fish Rhabdoviruses

    Directory of Open Access Journals (Sweden)

    Maureen K. Purcell

    2012-01-01

    Full Text Available Members of the family Rhabdoviridae are single-stranded RNA viruses and globally important pathogens of wild and cultured fish and thus relatively well studied in their respective hosts or other model systems. Here, we review the protective immune mechanisms that fish mount in response to rhabdovirus infections. Teleost fish possess the principal components of innate and adaptive immunity found in other vertebrates. Neutralizing antibodies are critical for long-term protection from fish rhabdoviruses, but several studies also indicate a role for cell-mediated immunity. Survival of acute rhabdoviral infection is also dependent on innate immunity, particularly the interferon (IFN system that is rapidly induced in response to infection. Paradoxically, rhabdoviruses are sensitive to the effects of IFN but virulent rhabdoviruses can continue to replicate owing to the abilities of the matrix (M protein to mediate host-cell shutoff and the non‑virion (NV protein to subvert programmed cell death and suppress functional IFN. While many basic features of the fish immune response to rhabdovirus infections are becoming better understood, much less is known about how factors in the environment affect the ecology of rhabdovirus infections in natural populations of aquatic animals.

  1. Host-to-host variation of ecological interactions in polymicrobial infections

    International Nuclear Information System (INIS)

    Mukherjee, Sayak; Seok, Sang-Cheol; Ray, Will C; Jayaprakash, C; Vieland, Veronica J; Das, Jayajit; Weimer, Kristin E; Swords, W Edward

    2015-01-01

    Host-to-host variability with respect to interactions between microorganisms and multicellular hosts are commonly observed in infection and in homeostasis. However, the majority of mechanistic models used to analyze host–microorganism relationships, as well as most of the ecological theories proposed to explain coevolution of hosts and microbes, are based on averages across a host population. By assuming that observed variations are random and independent, these models overlook the role of differences between hosts. Here, we analyze mechanisms underlying host-to-host variations of bacterial infection kinetics, using the well characterized experimental infection model of polymicrobial otitis media (OM) in chinchillas, in combination with population dynamic models and a maximum entropy (MaxEnt) based inference scheme. We find that the nature of the interactions between bacterial species critically regulates host-to-host variations in these interactions. Surprisingly, seemingly unrelated phenomena, such as the efficiency of individual bacterial species in utilizing nutrients for growth, and the microbe-specific host immune response, can become interdependent in a host population. The latter finding suggests a potential mechanism that could lead to selection of specific strains of bacterial species during the coevolution of the host immune response and the bacterial species. (paper)

  2. PATHOPHYSIOLOGY OF POSTOPERATIVE STRESS REACTION AND MODERN APPROACHES TO NUTRITIVE SUPPORT FOR CHILDREN IN POSTOPERATIVE PERIOD

    Directory of Open Access Journals (Sweden)

    P.V. Shumilov

    2010-01-01

    Full Text Available Enteral nutrition is a method best adjusted to human physiology for correcting disorders of homeostasis in the postoperative period. Untimely and inadequate correction of these disorders may fatally affect a child’s health and rates of the child’s further development. Understanding the laws of stress response generation is important in selecting an optimal nutritive support in the postoperative period. It is necessary to take account of neuro-endocrine-immune response, changing metabolism and an impaired function of the gastrointestinal tract. Modern methods of diagnostics and treatment make it possible to resolve most of the arising issues, but it requires physicians to take a comprehensive approach and have knowledge in many areas of theoretical and practical medicine. Key words: stress, metabolism, children, enteral nutrition. (Pediatric Pharmacology. – 2010; 7(3:36-45

  3. Thrombolysis in Postoperative Stroke.

    Science.gov (United States)

    Voelkel, Nicolas; Hubert, Nikolai Dominik; Backhaus, Roland; Haberl, Roman Ludwig; Hubert, Gordian Jan

    2017-11-01

    Intravenous thrombolysis (IVT) is beneficial in reducing disability in selected patients with acute ischemic stroke. There are numerous contraindications to IVT. One is recent surgery. The aim of this study was to analyze the safety of IVT in patients with postoperative stroke. Data of consecutive IVT patients from the Telemedical Project for Integrative Stroke Care thrombolysis registry (February 2003 to October 2014; n=4848) were retrospectively searched for keywords indicating preceding surgery. Patients were included if surgery was performed within the last 90 days before stroke. The primary outcome was defined as surgical site hemorrhage. Subgroups with major/minor surgery and recent/nonrecent surgery (within 10 days before IVT) were analyzed separately. One hundred thirty-four patients underwent surgical intervention before IVT. Surgery had been performed recently (days 1-10) in 49 (37%) and nonrecently (days 11-90) in 85 patients (63%). In 86 patients (64%), surgery was classified as major, and in 48 (36%) as minor. Nine patients (7%) developed surgical site hemorrhage after IVT, of whom 4 (3%) were serious, but none was fatal. One fatal bleeding occurred remotely from surgical area. Rate of surgical site hemorrhage was significantly higher in recent than in nonrecent surgery (14.3% versus 2.4%, respectively, odds ratio adjusted 10.73; 95% confidence interval, 1.88-61.27). Difference between patients with major and minor surgeries was less distinct (8.1% and 4.2%, respectively; odds ratio adjusted 4.03; 95% confidence interval, 0.65-25.04). Overall in-hospital mortality was 8.2%. Intracranial hemorrhage occurred in 9.7% and was asymptomatic in all cases. IVT may be administered safely in postoperative patients as off-label use after appropriate risk-benefit assessment. However, bleeding risk in surgical area should be taken into account particularly in patients who have undergone surgery shortly before stroke onset. © 2017 American Heart Association, Inc.

  4. The Inflammasome in Host Defense

    Directory of Open Access Journals (Sweden)

    Gang Chen

    2009-12-01

    Full Text Available Nod-like receptors have emerged as an important family of sensors in host defense. These receptors are expressed in macrophages, dendritic cells and monocytes and play an important role in microbial immunity. Some Nod-like receptors form the inflammasome, a protein complex that activates caspase-1 in response to several stimuli. Caspase-1 activation leads to processing and secretion of pro-inflammatory cytokines such as interleukin (IL-1β and IL-18. Here, we discuss recent advances in the inflammasome field with an emphasis on host defense. We also compare differential requirements for inflammasome activation in dendritic cells, macrophages and monocytes.

  5. Host response to biomaterials the impact of host response on biomaterial selection

    CERN Document Server

    Badylak, Stephen F

    2015-01-01

    Host Response to Biomaterials: The Impact of Host Response on Biomaterial Selection explains the various categories of biomaterials and their significance for clinical applications, focusing on the host response to each biomaterial. It is one of the first books to connect immunology and biomaterials with regard to host response. The text also explores the role of the immune system in host response, and covers the regulatory environment for biomaterials, along with the benefits of synthetic versus natural biomaterials, and the transition from simple to complex biomaterial solutions. Fiel

  6. Childhood Immunization

    Science.gov (United States)

    ... lowest levels in history, thanks to years of immunization. Children must get at least some vaccines before ... child provide protection for many years, adults need immunizations too. Centers for Disease Control and Prevention

  7. Immunizations - diabetes

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000331.htm Immunizations - diabetes To use the sharing features on this page, please enable JavaScript. Immunizations (vaccines or vaccinations) help protect you from some ...

  8. 舒芬太尼联合布比卡因对老年下肢骨科手术患者术后镇痛与免疫功能的影响%Effects of sufentanil combined with bupivacaine on postoperative analgesia and immunity function in elderly patients under lower extremity orthopaedic surgery

    Institute of Scientific and Technical Information of China (English)

    程惠平; 吴城; 张中伟; 陆惠根

    2013-01-01

    ,降低局部麻醉药物浓度,加快老年患者术后麻醉平面恢复,加快术后早期免疫功能的康复.%Objective To investigate effects of intrathecal injection of sufentanil combined with bupivacaine on postoperative analgesia and immunity function in elderly patients under lower extremity orthopaedic surgery.Methods Totally 60 elderly patients with ASA Ⅰ or Ⅲ under lower extremity orthopaedic surgery were randomly divided into two groups:bupivacaine and sufentanil group (each n =30).3 ml bupivacaine (2 ml 0.75% bupivacaine plus 1 ml 0.9% normal saline) were given in bupivacaine after successful spinal anesthesia and 3 ml sufentanil (1 ml 0.75 % bupivacaine plus 1 ml 0.9% normal saline and 1 ml with 5 μg sufentanil) were used in sufentanil group respectively.The anesthetic feeling and block level before operation recovery time were recorded postoperation.Visual analogue scale (VAS) and adverse reaction were recorded at 1,6,12,24 and 48 h after surgery.Cellular and humoral immunity function were recorded at the following time points:T0,the day before surgery; T1,the day after surgery; T2,the first 5 postoperative days; T3,the first 10 postoperative days; T4,the first 15 postoperative days.Results The sensory and motor block levels in sufentanil group were T9~~T10 and T11~T12 respectively,which were higher than in bupivacaine (T7~T8 and T8~T10).The recovery time in sufentanil group was shorter than in the bupivacaine (P<0.05).There were no significant differences in VAS scale between the two groups at any postoperative time points (P<0.05).The incidence of skin pruritus was higher in sufentanil group (6 cases) than in bupivacaine (P<0.05).There were significant differences in the indexes for the immune condition including CD3+,CD4+/CD3+,CD4/HLADR,CD8/HLADR,B-cell,NK-cell between time points of T2[(48.7±2.3)%,(33.4±1.8)%,(10.2±1.8)%,(0.75±0.07)%,(1.02±0.16)%,(3.12 ±0.19) %,(2.53±0.14)%,respectively] and T0

  9. Immunization Coverage

    Science.gov (United States)

    ... room/fact-sheets/detail/immunization-coverage","@context":"http://schema.org","@type":"Article"}; العربية 中文 français русский español ... Plan Global Health Observatory (GHO) data - Immunization More information on vaccines and immunization News 1 in 10 ...

  10. Alcohol, aging, and innate immunity.

    Science.gov (United States)

    Boule, Lisbeth A; Kovacs, Elizabeth J

    2017-07-01

    The global population is aging: in 2010, 8% of the population was older than 65 y, and that is expected to double to 16% by 2050. With advanced age comes a heightened prevalence of chronic diseases. Moreover, elderly humans fair worse after acute diseases, namely infection, leading to higher rates of infection-mediated mortality. Advanced age alters many aspects of both the innate and adaptive immune systems, leading to impaired responses to primary infection and poor development of immunologic memory. An often overlooked, yet increasingly common, behavior in older individuals is alcohol consumption. In fact, it has been estimated that >40% of older adults consume alcohol, and evidence reveals that >10% of this group is drinking more than the recommended limit by the National Institute on Alcohol Abuse and Alcoholism. Alcohol consumption, at any level, alters host immune responses, including changes in the number, phenotype, and function of innate and adaptive immune cells. Thus, understanding the effect of alcohol ingestion on the immune system of older individuals, who are already less capable of combating infection, merits further study. However, there is currently almost nothing known about how drinking alters innate immunity in older subjects, despite innate immune cells being critical for host defense, resolution of inflammation, and maintenance of immune homeostasis. Here, we review the effects of aging and alcohol consumption on innate immune cells independently and highlight the few studies that have examined the effects of alcohol ingestion in aged individuals. © Society for Leukocyte Biology.

  11. Immune escape strategies of malaria parasites

    Directory of Open Access Journals (Sweden)

    Pollyanna Stephanie Gomes

    2016-10-01

    Full Text Available Malaria is one of the most life-threatening infectious diseases worldwide. Immunity to malaria is slow and short-lived despite the repeated parasite exposure in endemic areas. Malaria parasites have evolved refined machinery to evade the immune system based on a range of genetic changes that include allelic variation, biomolecular exposure of proteins and intracellular replication. All of these features increase the probability of survival in both mosquitoes and the vertebrate host. Plasmodium species escape from the first immunological trap in its invertebrate vector host, the Anopheles mosquitoes. The parasites have to pass through various immunological barriers within the mosquito such as anti-microbial molecules and the mosquito microbiota in order to achieve successful transmission to the vertebrate host. Within these hosts, Plasmodium species employ various immune evasion strategies during different life cycle stages. Parasite persistence against the vertebrate immune response depends on the balance among virulence factors, pathology, metabolic cost of the host immune response, and the parasites ability to evade the immune response. In this review we discuss the strategies that Plasmodium parasites use to avoid the vertebrate host immune system and how they promote successful infection and transmission.

  12. The postoperative spine

    International Nuclear Information System (INIS)

    Anon.

    1985-01-01

    The failed back surgery syndrome (FBSS) is one of the most perplexing medical and medicoeconomic problems facing our health system today. In many studies reoperation rates tend to be between 10 and 20%, but as many as 20-45% 3 of patients may have persistent back or radicular pain following what was to have been definitive therapy. The causes for the FBSS are very complex. The Workmen's Compensation system and medicolegal trends toward very high settlements of litigation for injury have provided serious incentive for patients to remain symptomatic. It is difficult to analyze any statistical survey of symptomatic back patients without serious bias from this group of patients. Others suggest that patients with severe psychological problems, drug abuse, and alcoholism are inappropriately selected as surgical candidates. They believe that careful psychological evaluation of patients minimizes FBSS. Even if all extrinsic factors could be eliminated, the problem of failed back surgery would still be a major one. This chapter is based on a review of 300 postoperative lumbar spine multiplanar CT scans performed over a 15-month period. All patients had a complete set of axial images, with sagittal and coronal reformations photographed twice: optimized once for bone definition and once for soft-tissue contrast resolution

  13. Preoperative alcoholism and postoperative morbidity

    DEFF Research Database (Denmark)

    Tonnesen, H; Kehlet, H

    1999-01-01

    BACKGROUND: Preoperative risk assessment has become part of daily clinical practice, but preoperative alcohol abuse has not received much attention. METHODS: A Medline search was carried out to identify original papers published from 1967 to 1998. Relevant articles on postoperative morbidity...... in alcohol abusers were used to evaluate the evidence. RESULTS: Prospective and retrospective studies demonstrate a twofold to threefold increase in postoperative morbidity in alcohol abusers, the most frequent complications being infections, bleeding and cardiopulmonary insufficiency. Wound complications...... to postoperative morbidity. CONCLUSION: Alcohol consumption should be included in the preoperative assessment of likely postoperative outcome. Reduction of postoperative morbidity in alcohol abusers may include preoperative alcohol abstinence to improve organ function, or perioperative alcohol administration...

  14. Leishmania Hijacks Myeloid Cells for Immune Escape

    Directory of Open Access Journals (Sweden)

    María Martínez-López

    2018-05-01

    Full Text Available Protozoan parasites of the Leishmania genus are the causative agents of leishmaniasis, a group of neglected tropical diseases whose clinical manifestations vary depending on the infectious Leishmania species but also on host factors. Recognition of the parasite by host myeloid immune cells is a key to trigger an effective Leishmania-specific immunity. However, the parasite is able to persist in host myeloid cells by evading, delaying and manipulating host immunity in order to escape host resistance and ensure its transmission. Neutrophils are first in infiltrating infection sites and could act either favoring or protecting against infection, depending on factors such as the genetic background of the host or the parasite species. Macrophages are the main host cells where the parasites grow and divide. However, macrophages are also the main effector population involved in parasite clearance. Parasite elimination by macrophages requires the priming and development of an effector Th1 adaptive immunity driven by specific subtypes of dendritic cells. Herein, we will provide a comprehensive outline of how myeloid cells regulate innate and adaptive immunity against Leishmania, and the mechanisms used by the parasites to promote their evasion and sabotage. Understanding the interactions between Leishmania and the host myeloid cells may lead to the development of new therapeutic approaches and improved vaccination to leishmaniases, an important worldwide health problem in which current therapeutic or preventive approaches are limited.

  15. The effects of transfusion of irradiated blood upon cellular immune response in patients underwent open heart surgery

    International Nuclear Information System (INIS)

    Togashi, Ken-ichi; Nakazawa, Satoshi; Moro, Hisanaga; Yazawa, Masatomo; Kanazawa, Hiroshi; Hayashi, Jun-ichi; Yamazaki, Yoshihiko; Eguchi, Shoji

    1989-01-01

    The purpose of this paper is to demonstrate the effect of the transfusion of blood received 1500 rad exposure upon the immune response in 14 patients underwent various type of cardiac surgery. 13 patients received known amounts banked blood and irradiated fresh blood, while one patient received a lot of amounts of banked and irradiated and non-irradiated fresh blood. The authors studied the numbers of lymphocytes as well as lymphocyte subsets such as pan-T cells, B cells, helper/inducer T cells (T H/I ), cytotoxic/supressor T cells (T C/S ), active T cells, natural killer (NK) cells and NK cell activity during two weeks after surgeries. In all 14 patients, pan-T lymphocytes decreased markedly in a few days after surgeries, but increased to higher levels on the eight postoperative day than the levels preoperatively. T H/I and T C/S lymphocytes changed on the similar pattern as pan-T lymphocytes. Active T and B cells did not change significantly in two weeks. The number and activity of NK cells gave the lowest levels on the second postoperative day and did not recovery to the preoperative levels in two weeks. One patient received non-irradiated fresh blood showed the similar immune response as other 13 patients, while he gave the lower levels than others did. This patient died of graft-versus-host disease (GVHD)-like syndrome on the 36th postoperative day. It may be thought that the transfusion of irradiated blood would prevent the host from GVHD and gave the better effects on the immune response than that of non-irradiated blood following open-heart surgeries. (author)

  16. Gene Expression Contributes to the Recent Evolution of Host Resistance in a Model Host Parasite System

    Directory of Open Access Journals (Sweden)

    Brian K. Lohman

    2017-09-01

    Full Text Available Heritable population differences in immune gene expression following infection can reveal mechanisms of host immune evolution. We compared gene expression in infected and uninfected threespine stickleback (Gasterosteus aculeatus from two natural populations that differ in resistance to a native cestode parasite, Schistocephalus solidus. Genes in both the innate and adaptive immune system were differentially expressed as a function of host population, infection status, and their interaction. These genes were enriched for loci controlling immune functions known to differ between host populations or in response to infection. Coexpression network analysis identified two distinct processes contributing to resistance: parasite survival and suppression of growth. Comparing networks between populations showed resistant fish have a dynamic expression profile while susceptible fish are static. In summary, recent evolutionary divergence between two vertebrate populations has generated population-specific gene expression responses to parasite infection, affecting parasite establishment and growth.

  17. Immunizing Children

    Directory of Open Access Journals (Sweden)

    Geraldine Jody Macdonald

    2014-11-01

    Full Text Available This article addresses the complex contexts within which Canadian health professionals engage in immunizing children and focuses on the Canadian practice guidelines and current scientific evidence that direct Canadian health professional competencies. The article begins by presenting two current global vaccine initiatives and links these to immunization in Canada. A selected literature review identifies current best immunization practices. With the purpose of promoting quality improvement, three key Canadian immunization competencies for health professional are highlighted: communication with parents, including those who are experiencing vaccine hesitancy; administration of immunizing agents; and documentation of immunizations. Health professionals are encouraged to reflect on immunization competencies and ensure evidence-based practices underpin vaccine delivery in their primary care settings.

  18. A rare disease mimics postoperative bile leakage: Invasive aspergillosis.

    Science.gov (United States)

    Yazar, Fatih Mehmet; Urfalıoğlu, Aykut; Boran, Ömer Faruk; Sayar, Hamide; Kanat, Burhan Hakan; Emre, Arif; Cengiz, Emrah; Bülbüloğlu, Ertan

    2016-09-01

    Aspergillus fungi can cause serious infections, including intra-abdominal infection, particularly in patients with compromised immune system. Described in the present report is case of 46-year-old female patient who had undergone laparoscopic cholecystectomy (LC) at another healthcare facility. In early postoperative period, she had increasing complaints of swelling, nausea, and vomiting. On postoperative 19th day, she was referred to our clinic with diagnosis of acute abdomen. Surgery was performed with suspected possibility of bile leakage. However, pathological examination of soft, yellow-green mass found in subhepatic space determined it was fungus ball caused by fungi of the genus Aspergillus. Patient was diagnosed postoperative intra-abdominal aspergillosis (IAA).

  19. Ranitidine improves postoperative suppression of antibody response to preoperative vaccination

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Hammer, J H; Moesgaard, F

    1992-01-01

    The effect of the histamine-2 receptor antagonist ranitidine (100 mg intravenously every 12 hours for 72 hours) on postoperative serum antibody responses to preoperative immunization with six limit of flocculation tetanus toxoid and six limit of flocculation diphtheria toxoid was assessed...... in a double-blind, placebo-controlled randomized study in 26 patients undergoing major abdominal surgery. The preoperative antitetanus antibody level was less than 0.1 IU/ml in all patients, and they were inoculated with both antigens 48 hours before surgery. Serum samples for analysis of antitetanus toxoid...... and antidiphtheria toxoid were drawn before skin incision and on postoperative days 1, 3, 5, 7, 10, 14, 21, and 28. Ranitidine significantly increased the postoperative antibody response to tetanus toxoid, (p less than 0.01) and insignificantly increased that to diphtheria toxoid vaccination (p less than 0...

  20. POSTOPERATIVE NAUSEA AND VOMITING | Yusufu | Annals of ...

    African Journals Online (AJOL)

    Antiemetics, acupuncture and other drugs are used to prevent and treat postoperative nausea and vomiting. Those that manage patients in the postoperative period should endeavour to make postoperative nausea and vomiting as unacceptable as postoperative pain. Key words: Postoperative, Nausea, Vomiting, Narcotics, ...

  1. Postoperative Ileus in the Elderly

    Directory of Open Access Journals (Sweden)

    Chih-Peng Tu

    2014-03-01

    Full Text Available Postoperative ileus is among the most common complications after surgery. Aging is associated with an increased colonic transit time, and anesthetic disturbance to colonic motility is often aggravated in the elderly. Postoperative ileus increases morbidity, prolongs the length of hospital stay, and constitutes a significant economic burden on the healthcare system. Multimodal enhanced recovery protocols, or fast-track surgeries, have been developed to improve postoperative recovery. Patient education, avoidance of perioperative fluid overload, selective use of nasogastric decompression, early ambulation, adopting a minimally invasive approach, early initiation of clear fluids, and gum chewing are all possible measures to reduce postoperative ileus. Thoracic epidural anesthesia is a well-established technique to hasten recovery, whereas insufficient data are available to ascertain the safety and efficacy of opioid-sparing analgesia in the elderly. The evidence is clear that traditional prokinetic medications are not helpful in the treatment or prevention of postoperative ileus. Early results suggest that alvimopan is a promising agent to reverse opioid-induced ileus. Since postoperative ileus is a multifactorial condition, a concerted effort is therefore necessary to prevent or decrease the duration of postoperative ileus using multimodal strategies.

  2. Postoperative imaging of the shoulder

    International Nuclear Information System (INIS)

    Woertler, K.; Rummeny, E.J.

    2004-01-01

    Correct interpretation of imaging findings in the postoperative shoulder is impaired by surgical distortion of normal anatomy and possible artifacts. Advanced postoperative imaging of the shoulder in addition to the selection of the best suited modality necessitates familiarity with the surgical procedure that has been performed and its consecutive morphological changes. This article reviews the most common arthroscopic and open techniques used for treatment of shoulder instability, lesions of the superior labral-bicipital complex, primery impingement, and rotator cuff tears, their typical postoperative imaging findings, as well as the diagnostic performance of cross sectional imaging techniques in the detection of recurrent lesions and complications. (orig.) [de

  3. Spirochetal Lipoproteins and Immune Evasion

    Science.gov (United States)

    Christodoulides, Alexei; Boyadjian, Ani; Kelesidis, Theodoros

    2017-01-01

    Spirochetes are a major threat to public health. However, the exact pathogenesis of spirochetal diseases remains unclear. Spirochetes express lipoproteins that often determine the cross talk between the host and spirochetes. Lipoproteins are pro-inflammatory, modulatory of immune responses, and enable the spirochetes to evade the immune system. In this article, we review the modulatory effects of spirochetal lipoproteins related to immune evasion. Understanding lipoprotein-induced immunomodulation will aid in elucidating innate pathogenesis processes and subsequent adaptive mechanisms potentially relevant to spirochetal disease vaccine development and treatment. PMID:28424696

  4. Bacterial pathogen manipulation of host membrane trafficking.

    Science.gov (United States)

    Asrat, Seblewongel; de Jesús, Dennise A; Hempstead, Andrew D; Ramabhadran, Vinay; Isberg, Ralph R

    2014-01-01

    Pathogens use a vast number of strategies to alter host membrane dynamics. Targeting the host membrane machinery is important for the survival and pathogenesis of several extracellular, vacuolar, and cytosolic bacteria. Membrane manipulation promotes bacterial replication while suppressing host responses, allowing the bacterium to thrive in a hostile environment. This review provides a comprehensive summary of various strategies used by both extracellular and intracellular bacteria to hijack host membrane trafficking machinery. We start with mechanisms used by bacteria to alter the plasma membrane, delve into the hijacking of various vesicle trafficking pathways, and conclude by summarizing bacterial adaptation to host immune responses. Understanding bacterial manipulation of host membrane trafficking provides insights into bacterial pathogenesis and uncovers the molecular mechanisms behind various processes within a eukaryotic cell.

  5. Postoperative MRI of the ankle; Postoperative Magnetresonanztomographie des Sprunggelenks

    Energy Technology Data Exchange (ETDEWEB)

    Sharabianlou Korth, M.; Fritz, L.B. [Rheinlandaerzte, Willich (Germany)

    2017-11-15

    Postoperative imaging of the ankle can be challenging, even for the experienced radiologist. Pathological and postoperative changes to the primarily complex anatomy of the ankle with its great variety of bone structures, tendons, ligaments, and soft tissue in a very limited space may cause great difficulty in differentiating underlying pathology from expected postoperative changes and artifacts, especially in magnetic resonance imaging (MRI). Selecting the appropriate radiological modality is key to making the correct diagnosis. Therefore, knowledge of the initial and current symptoms is just as important as familiarity with the most frequently performed operations in the ankle. This article aims to give its reader a summary of the most important and frequently performed operation techniques of the ankle and discusses the expected appearance and possible complications in postoperative imaging. (orig.) [German] Die postoperative radiologische Bildgebung des Sprunggelenks kann auch fuer den erfahrenen Radiologen eine besondere Herausforderung darstellen. Die komplex aufgebaute Anatomie des Sprunggelenks, mit seinen multiplen Gelenkflaechen, Sehnen, Baendern und neurovaskulaeren Strukturen auf engstem Raum, kann durch Operationen signifikant veraendert und insbesondere in der Magnetresonanztomographie (MRT) verfaelscht dargestellt werden. Fuer eine fundierte Befundung und Beurteilung der Operationsergebnisse ist die Kenntnis der praeoperativen Diagnose, Zeitpunkt und Technik der durchgefuehrten Operation(en) sowie der aktuellen klinischen Symptomatik von grosser Bedeutung. Dieser Artikel konzentriert sich auf zu erwartende radiologische Veraenderungen und gibt Tipps zur Befundung der postoperativen MRT des Sprunggelenks bei einer Auswahl relevanter operativer Eingriffe. Zudem wird auf moegliche postoperative Komplikationen und ihre radiologische Darstellung hingewiesen. (orig.)

  6. The Immune System: Basis of so much Health and Disease: 3. Adaptive Immunity.

    Science.gov (United States)

    Scully, Crispian; Georgakopoulou, Eleni A; Hassona, Yazan

    2017-04-01

    The immune system is the body’s primary defence mechanism against infections, and disturbances in the system can cause disease if the system fails in defence functions (in immunocompromised people), or if the activity is detrimental to the host (as in auto-immune and auto-inflammatory states). A healthy immune system is also essential to normal health of dental and oral tissues. This series presents the basics for the understanding of the immune system; this article covers adaptive immunity. Clinical relevance: Dental clinicians need a basic understanding of the immune system as it underlies health and disease.

  7. Postoperative radiographic evaluation of vascularized fibular grafts

    International Nuclear Information System (INIS)

    Manaster, B.J.; Coleman, D.A.; Bell, D.A.

    1989-01-01

    This paper reports on thirty-five patients with free vascularized fibular grafts examined postoperatively with plain radiography. Early graft incorporation is seen as a fuzziness of the cortex at the site of its insertion into the host bone. Causes of failure in grafting for bone defects include graft fracture, hardware failure, and infection. A high percentage of complications or at least delayed unions occurred when vascularized fibular grafts were used to fill defects in the lower extremity. Conversely, upper extremity defects bridged by vascularized grafts heal quickly and hypertrophy. Vascularized grafts placed in the femoral head and neck for a vascular necrosis incorporate early on their superior aspect. The osseous tunnel in which they are placed is normally wider than the graft and often becomes sclerotic; this appearance does not represent nonunion

  8. Glycoconjugates in host-helminth interactions

    Directory of Open Access Journals (Sweden)

    Nina Salinger Prasanphanich

    2013-08-01

    Full Text Available Helminths are multicellular parasitic worms that comprise a major class of human pathogens and cause an immense amount of suffering worldwide. Helminths possess an abundance of complex and unique glycoconjugates that interact with both the innate and adaptive arms of immunity in definitive and intermediate hosts. These glycoconjugates represent a major untapped reservoir of immunomodulatory compounds, which have the potential to treat autoimmune and inflammatory disorders, and antigenic glycans, which could be exploited as vaccines and diagnostics. This review will survey current knowledge of the interactions between helminth glycans and host immunity and highlight the gaps in our understanding which are relevant to advancing therapeutics, vaccine development and diagnostics.

  9. Postoperative MRI of the ankle

    International Nuclear Information System (INIS)

    Sharabianlou Korth, M.; Fritz, L.B.

    2017-01-01

    Postoperative imaging of the ankle can be challenging, even for the experienced radiologist. Pathological and postoperative changes to the primarily complex anatomy of the ankle with its great variety of bone structures, tendons, ligaments, and soft tissue in a very limited space may cause great difficulty in differentiating underlying pathology from expected postoperative changes and artifacts, especially in magnetic resonance imaging (MRI). Selecting the appropriate radiological modality is key to making the correct diagnosis. Therefore, knowledge of the initial and current symptoms is just as important as familiarity with the most frequently performed operations in the ankle. This article aims to give its reader a summary of the most important and frequently performed operation techniques of the ankle and discusses the expected appearance and possible complications in postoperative imaging. (orig.) [de

  10. Immune reaction and colorectal cancer: friends or foes?

    Science.gov (United States)

    Formica, Vincenzo; Cereda, Vittore; Nardecchia, Antonella; Tesauro, Manfredi; Roselli, Mario

    2014-09-21

    The potential clinical impact of enhancing antitumor immunity is increasingly recognized in oncology therapeutics for solid tumors. Colorectal cancer is one of the most studied neoplasms for the tumor-host immunity relationship. Although immune cell populations involved in such a relationship and their prognostic role in colorectal cancer development have clearly been identified, still no approved therapies based on host immunity intensification have so far been introduced in clinical practice. Moreover, a recognized risk in enhancing immune reaction for colitis-associated colorectal cancer development has limited the emphasis of this approach. The aim of the present review is to discuss immune components involved in the host immune reaction against colorectal cancer and analyze the fine balance between pro-tumoral and anti-tumoral effect of immunity in this model of disease.

  11. Zinc and immunity: An essential interrelation.

    Science.gov (United States)

    Maares, Maria; Haase, Hajo

    2016-12-01

    The significance of the essential trace element zinc for immune function has been known for several decades. Zinc deficiency affects immune cells, resulting in altered host defense, increased risk of inflammation, and even death. The micronutrient zinc is important for maintenance and development of immune cells of both the innate and adaptive immune system. A disrupted zinc homeostasis affects these cells, leading to impaired formation, activation, and maturation of lymphocytes, disturbed intercellular communication via cytokines, and weakened innate host defense via phagocytosis and oxidative burst. This review outlines the connection between zinc and immunity by giving a survey on the major roles of zinc in immune cell function, and their potential consequences in vivo. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Immune Evasion by Epstein-Barr Virus

    NARCIS (Netherlands)

    Ressing, Maaike E; van Gent, Michiel; Gram, Anna M; Hooykaas, Marjolein J G; Piersma, Sytse J; Wiertz, EJHJ

    2015-01-01

    Epstein-Bar virus (EBV) is widespread within the human population with over 90% of adults being infected. In response to primary EBV infection, the host mounts an antiviral immune response comprising both innate and adaptive effector functions. Although the immune system can control EBV infection to

  13. Early nutrition and immunity - progress and perspectives

    NARCIS (Netherlands)

    Calder, Philip C.; Krauss-Etschmann, Susanne; de Jong, Esther C.; Dupont, Christophe; Frick, Julia-Stefanie; Frokiaer, Hanne; Heinrich, Joachim; Garn, Holger; Koletzko, Sibylle; Lack, Gideon; Mattelio, Gianluca; Renz, Harald; Sangild, Per T.; Schrezenmeir, Jürgen; Stulnig, Thomas M.; Thymann, Thomas; Wold, Agnes E.; Koletzko, Berthold

    2006-01-01

    The immune system exists to protect the host against pathogenic organisms and highly complex pathways of recognition, response, elimination and memory have evolved in order to fulfil this role. The immune system also acts to ensure tolerance to 'self', to food and other environmental components, and

  14. Immunity to gastrointestinal nematode infections

    DEFF Research Database (Denmark)

    Sorobetea, D.; Svensson Frej, M.; Grencis, R.

    2018-01-01

    Numerous species of nematodes have evolved to inhabit the gastrointestinal tract of animals and humans, with over a billion of the world's population infected with at least one species. These large multicellular pathogens present a considerable and complex challenge to the host immune system give...

  15. Impact of early postoperative enteral nutrition on clinical outcomes in patients with gastric cancer.

    Science.gov (United States)

    Li, B; Liu, H Y; Guo, S H; Sun, P; Gong, F M; Jia, B Q

    2015-06-29

    The impact of early enteral nutrition (EEN) on clinical outcomes of gastric cancer patients was investigated. Three hundred pa-tients undergoing gastric cancer surgery from July 2010 to May 2014 were randomly divided into experimental and control groups (n = 150/group). Experimental group patients received enteral nutrition in water during the early postoperative period. Control group patients received conventional perioperative treatment. Patients' clinical outcomes, post-operative immune function, and nutritional statuses were compared, which revealed that the postoperative fever duration (80.2 ± 6.0 vs 88.1 ± 8.1 h, P 0.05]. At postoperative days 3 and 7, the CD3(+), CD4(+), natural killer cell, albumin, and prealbumin levels and CD4(+)/CD8(+) ra-tio were significantly higher in the experimental group than the control group (all P nutritional status and immune function and promote early recovery of intestinal function in patients with gastric cancer.

  16. Demonstration and suppression of a radioresistant host-versus-graft reaction

    International Nuclear Information System (INIS)

    Thierfelder, S.; Roessler, R. v.; Ruppelt, W.

    1975-01-01

    The possibilities of suppressing and measuring a radioresistant host-versus-graft reaction are described. According to the authors, the host-versus-graft immune reaction may outlast whole-body irradiation at high doses. (BSC/AK) [de

  17. Immune System

    Science.gov (United States)

    A properly functioning immune system is essential to good health. It defends the body against infectious agents and in some cases tumor cells. Individuals with immune deficiencies resulting from genetic defects, diseases (e.g., AIDS, leukemia), or drug therapies are more suscepti...

  18. Immune response to H pylori

    Science.gov (United States)

    Suarez, Giovanni; Reyes, Victor E; Beswick, Ellen J

    2006-01-01

    The gastric mucosa separates the underlying tissue from the vast array of antigens that traffic through the stomach lumen. While the extreme pH of this environment is essential in aiding the activation of enzymes and food digestion, it also renders the gastric epithelium free from bacterial colonization, with the exception of one important human pathogen, H pylori. This bacterium has developed mechanisms to survive the harsh environment of the stomach, actively move through the mucosal layer, attach to the epithelium, evade immune responses, and achieve persistent colonization. While a hallmark of this infection is a marked inflammatory response with the infiltration of various immune cells into the infected gastric mucosa, the host immune response is unable to clear the infection and may actually contribute to the associated pathogenesis. Here, we review the host responses involved during infection with H pylori and how they are influenced by this bacterium. PMID:17007009

  19. Immune tolerance in radiation chimeras

    International Nuclear Information System (INIS)

    Awaya, Kazuhiko; Kuniki, Hiromichi; Neki, Miyuki

    1978-01-01

    Establishment of immune tolerance in radiation chimeras and the mechanism of maintaining it were discussed from certain points. Semiallogeneic radiation chimeras are mostly of long-living, and the hematopoietic organ of this individual consists mainly of the cells derived from the marrow donor, i. e., F 1 -type cells. F 1 -type lymphocytes can distinguish parental strain cells from themselves. In these chimeras, a F 1 -skin graft maintains to be fresh as long as the host is alive, showing immune tolerance effective through its life. In establishment and maintenance of this immune tolerance, the suppressing mechanism of host-type or F 1 -type seems to be involved. The allogeneic radiation chimera has very poor long-survival rate compared with that of the semiallogeneic radiation chimera. To raise this survival rate, efforts are now being made from the immunological point of view. (Ueda, J.)

  20. Regulation of intestinal homeostasis and immunity with probiotic lactobacilli.

    Science.gov (United States)

    van Baarlen, Peter; Wells, Jerry M; Kleerebezem, Michiel

    2013-05-01

    The gut microbiota provide important stimuli to the human innate and adaptive immune system and co-mediate metabolic and immune homeostasis. Probiotic bacteria can be regarded as part of the natural human microbiota, and have been associated with improving homeostasis, albeit with different levels of success. Composition of microbiota, probiotic strain identity, and host genetic differences may account for differential modulation of immune responses by probiotics. Here, we review the mechanisms of immunomodulating capacities of specific probiotic strains, the responses they can induce in the host, and how microbiota and genetic differences between individuals may co-influence host responses and immune homeostasis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. A water soluble fraction capable of regulating the immunity reactions of a host against allogenic cells or tissues, the pharmaceutical preparations which contain this fraction and a procedure for the preparation of the latter

    International Nuclear Information System (INIS)

    1980-01-01

    The preparation is described of non-toxic bone marrow cell suspensions containing a marrow-regulating factor, which are suitable for intravenous injection in patients with serious hematopoietic disturbances or radiation syndrome. The marrow-regulating factor conditions the bone marrow in a manner which enhances the success of bone marrow transplantation in donor-incompatible or semicompatible hosts. The extensive testing of this pharmaceutical preparation in irradiated mice is described and a toxicity study reported. (Auth.)

  2. Lymphoma: Immune Evasion Strategies

    International Nuclear Information System (INIS)

    Upadhyay, Ranjan; Hammerich, Linda; Peng, Paul; Brown, Brian; Merad, Miriam; Brody, Joshua D.

    2015-01-01

    While the cellular origin of lymphoma is often characterized by chromosomal translocations and other genetic aberrations, its growth and development into a malignant neoplasm is highly dependent upon its ability to escape natural host defenses. Neoplastic cells interact with a variety of non-malignant cells in the tumor milieu to create an immunosuppressive microenvironment. The resulting functional impairment and dysregulation of tumor-associated immune cells not only allows for passive growth of the malignancy but may even provide active growth signals upon which the tumor subsequently becomes dependent. In the past decade, the success of immune checkpoint blockade and adoptive cell transfer for relapsed or refractory lymphomas has validated immunotherapy as a possible treatment cornerstone. Here, we review the mechanisms by which lymphomas have been found to evade and even reprogram the immune system, including alterations in surface molecules, recruitment of immunosuppressive subpopulations, and secretion of anti-inflammatory factors. A fundamental understanding of the immune evasion strategies utilized by lymphomas may lead to better prognostic markers and guide the development of targeted interventions that are both safer and more effective than current standards of care

  3. Lymphoma: Immune Evasion Strategies

    Energy Technology Data Exchange (ETDEWEB)

    Upadhyay, Ranjan; Hammerich, Linda; Peng, Paul [Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Brown, Brian [Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Merad, Miriam [Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Brody, Joshua D., E-mail: joshua.brody@mssm.edu [Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States)

    2015-04-30

    While the cellular origin of lymphoma is often characterized by chromosomal translocations and other genetic aberrations, its growth and development into a malignant neoplasm is highly dependent upon its ability to escape natural host defenses. Neoplastic cells interact with a variety of non-malignant cells in the tumor milieu to create an immunosuppressive microenvironment. The resulting functional impairment and dysregulation of tumor-associated immune cells not only allows for passive growth of the malignancy but may even provide active growth signals upon which the tumor subsequently becomes dependent. In the past decade, the success of immune checkpoint blockade and adoptive cell transfer for relapsed or refractory lymphomas has validated immunotherapy as a possible treatment cornerstone. Here, we review the mechanisms by which lymphomas have been found to evade and even reprogram the immune system, including alterations in surface molecules, recruitment of immunosuppressive subpopulations, and secretion of anti-inflammatory factors. A fundamental understanding of the immune evasion strategies utilized by lymphomas may lead to better prognostic markers and guide the development of targeted interventions that are both safer and more effective than current standards of care.

  4. Host-pathogen interactions in typhoid fever

    NARCIS (Netherlands)

    de Jong, H.K.

    2015-01-01

    This thesis focuses on host-pathogen interactions in Salmonella Typhi and Burkholderia pseudomallei infections and explores the interplay between these bacteria and the innate immune system. Typhoid fever is one of the most common causes of bacterial infection in low-income countries. With adequate

  5. Host Genetics: Fine-Tuning Innate Signaling

    OpenAIRE

    Fellay, Jacques; Goldstein, David B.

    2007-01-01

    A polymorphism modulating innate immunity signal transduction has recently been shown to influence human susceptibility to many different infections, providing one more indication of the potential of host genetics to reveal physiological pathways and mechanisms that influence resistance to infectious diseases.

  6. Immunity booster

    International Nuclear Information System (INIS)

    Stefanescu, Ioan; Titescu, Gheorghe; Tamaian, Radu; Haulica, Ion; Bild, Walther

    2002-01-01

    The immunity booster is, according to its patent description, microbiologically pure water with an D/(D+H) isotopic concentration of 100 ppm, with physical-chemical characteristics similar to those of distilled water. It is obtained by sterilization of a mixture of deuterium depleted water, with a 25 ppm isotopic concentration, with distilled water in a volume ratio of 4:6. Unlike natural immunity boosters (bacterial agents as Bacillus Chalmette-Guerin, Corynebacterium parvum; lipopolysaccharides; human immunoglobulin) or synthetical products (levamysol; isoprinosyne with immunostimulating action), which cause hypersensitivity and shocks, thrill, fever, sickness and the immunity complex disease, the water of 100 ppm D/(D + H) isotopic concentration is a toxicity free product. The testing for immune reaction of the immunity booster led to the following results: - an increase of cell action capacity in the first immunity shielding stage (macrophages), as evidenced by stimulation of a number of essential characterizing parameters, as well as of the phagocytosis capacity, bactericide capacity, and opsonic capacity of serum; - an increase of the number of leucocyte particularly of the granulocyte in peripheral blood, produced especially when medullar toxic agents like caryolysine are used; - it hinders the effect of lowering the number of erythrocytes in peripheral blood produced by experimentally induced chronic inflammation; - an increase of nonspecific immunity defence capacity against specific bacterial aggression of both Gram-positive bacteria (Streptococcus pneumoniae 558 ) and of the Gram-negative ones (Klebsiella pneumoniae 507 ); - an increase of immunity - stimulating activity (proinflamatory), like that of levamisole as evidenced by the test of stimulation of experimentally induced inflammation by means of carrageenan. The following advantages of the immunity booster are stressed: - it is toxicity free and side effect free; - can be orally administrated as

  7. Postoperative ileus: a preventable event

    DEFF Research Database (Denmark)

    Holte, Kathrine; Kehlet, H

    2000-01-01

    BACKGROUND: Postoperative ileus has traditionally been accepted as a normal response to tissue injury. No data support any beneficial effect of ileus and indeed it may contribute to delayed recovery and prolonged hospital stay. Efforts should, therefore, be made to reduce such ileus. METHODS......: Material was identified from a Medline search of the literature, previous review articles and references cited in original papers. This paper updates knowledge on the pathophysiology and treatment of postoperative ileus. RESULTS AND CONCLUSION: Pathogenesis mainly involves inhibitory neural reflexes...... only cisapride is proven beneficial; the effect of early enteral feeding remains unclear. However, postoperative ileus may be greatly reduced when all of the above are combined in a multimodal rehabilitation strategy....

  8. Alcohol abuse and postoperative morbidity

    DEFF Research Database (Denmark)

    Tønnesen, Hanne

    2003-01-01

    Patients who drink too much have more complications after surgery. The aim of this thesis was to evaluate the evidence, possible mechanisms, and prevention of the increased postoperative morbidity in alcohol abusers, defined by a consumption of at least five drinks per day. The literature could...... be criticised for several methodological flaws. Nevertheless, the results are in agreement showing moderate to strong evidence of increased postoperative morbidity after surgical procedures on alcohol abusers. There is weak to moderate evidence of increased postoperative mortality, hospital stay, and re......-operation. The personal and economic consequences are tremendous. The incidence of alcohol abusers undergoing surgery was 7% to 49%, according to gender and diagnosis. They have been identified by a self-reported alcohol intake, which implies the possibility of underestimation. Alcohol markers could be used for a more...

  9. Intestinal commensal microbes as immune modulators.

    Science.gov (United States)

    Ivanov, Ivaylo I; Honda, Kenya

    2012-10-18

    Commensal bacteria are necessary for the development and maintenance of a healthy immune system. Harnessing the ability of microbiota to affect host immunity is considered an important therapeutic strategy for many mucosal and nonmucosal immune-related conditions, such as inflammatory bowel diseases (IBDs), celiac disease, metabolic syndrome, diabetes, and microbial infections. In addition to well-established immunostimulatory effects of the microbiota, the presence of individual mutualistic commensal bacteria with immunomodulatory effects has been described. These organisms are permanent members of the commensal microbiota and affect host immune homeostasis in specific ways. Identification of individual examples of such immunomodulatory commensals and understanding their mechanisms of interaction with the host will be invaluable in designing therapeutic strategies to reverse intestinal dysbiosis and recover immunological homeostasis. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Effect of practical use of preoperative immunonutrition with Impact on prevention of postoperative pneumonia after esophagectomy

    International Nuclear Information System (INIS)

    Kano, Masayuki; Nabeya, Yoshihiro; Akutsu, Yasunori; Shuto, Kiyohiko; Uesato, Masaya; Miyazawa, Yukimasa; Matsubara, Hisahiro

    2009-01-01

    To clarify the clinical benefits of administering immune-enhancing diet, Impact, we examined retrospectively the effect of preoperative immunonutrition with Impact on prevention of postoperative pneumonia after esophagectomy. In 47 patients without preoperative radiotherapy, no patient who preoperatively administered Impact ≥2,250 mL failed to develop pneumonia. The patients whose postoperative hospital stay was more than 30 days were administered Impact ≤2,000 mL except for one case. These results suggest that even preoperative administration of less amount of Impact than an estimated maximum dose, depending on patients' condition, may be beneficial to prevent postoperative pneumonia and a long hospital stay after surgery. (author)

  11. Deceptive Imprinting and Immune Refocusing in Vaccine Design

    Science.gov (United States)

    A large number of the world’s most widespread and problematic pathogens evade host immune responses by inducing strain specific immunity to immunodominant epitopes with high mutation rates capable of altering antigenic profiles. The immune system appears to be decoyed into reacting to these immunod...

  12. Regulation of innate and adaptive immunity by the commensal microbiota

    OpenAIRE

    Jarchum, Irene; Pamer, Eric G.

    2011-01-01

    The microbial communities that inhabit the intestinal tract are essential for mammalian health. Communication between the microbiota and the host establishes and maintains immune homeostasis, enabling protective immune responses against pathogens while preventing adverse inflammatory responses to harmless commensal microbes. Specific bacteria, such as segmented filamentous bacteria, Clostridium species, and Bacteroides fragilis, are key contributors to immune homeostasis in the gut. The cellu...

  13. Immune modulation by dendritic-cell-based cancer vaccines

    Indian Academy of Sciences (India)

    The interplay between host immunity and tumour cells has opened the possibility of targeting tumour cells bymodulation of the human immune system. Cancer immunotherapy involves the treatment of a tumour by utilizing therecombinant human immune system components to target the pro-tumour microenvironment or by ...

  14. Comparison of the effects of SAG-M and whole-blood transfusions on postoperative suppression of delayed hypersensitivity

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Hammer, J H; Moesgaard, F

    1991-01-01

    The influence of perioperative whole-blood transfusion and transfusion with erythrocyte suspension (SAG-M blood) on postoperative depression of cell-mediated immunity (CMI) was investigated in 67 patients who underwent elective resection for colorectal cancer. Cell-mediated immunity was assessed...

  15. Oxygen therapy reduces postoperative tachycardia

    DEFF Research Database (Denmark)

    Stausholm, K; Kehlet, H; Rosenberg, J

    1995-01-01

    Concomitant hypoxaemia and tachycardia in the postoperative period is unfavourable for the myocardium. Since hypoxaemia per se may be involved in the pathogenesis of postoperative tachycardia, we have studied the effect of oxygen therapy on tachycardia in 12 patients randomly allocated to blinded...... air or oxygen by facemask on the second or third day after major surgery. Inclusion criteria were arterial hypoxaemia (oxygen saturation 90 beat.min-1). Each patient responded similarly to oxygen therapy: an increase in arterial oxygen saturation and a decrease...... in heart rate (p oxygen has a positive effect on the cardiac oxygen delivery and demand balance....

  16. Proteinaceous molecules mediating Bifidobacterium-host interactions

    Directory of Open Access Journals (Sweden)

    Lorena Ruiz

    2016-08-01

    Full Text Available Bifidobacteria are commensal microoganisms found in the gastrointestinal tract.Several strains have been attributed beneficial traits at local and systemic levels, through pathogen exclusion or immune modulation, among other benefits. This has promoted a growing industrial and scientific interest in bifidobacteria as probiotic supplements. However, the molecular mechanisms mediating this cross-talk with the human host remain unknown. High-throughput technologies, from functional genomics to transcriptomics, proteomics and interactomics coupled to the development of both in vitro and in vivo models to study the dynamics of the intestinal microbiota and their effects on host cells, have eased the identification of key molecules in these interactions. Numerous secreted or surface-associated proteins or peptides have been identified as potential mediators of bifidobacteria-host interactions and molecular cross-talk, directly participating in sensing environmental factors, promoting intestinal colonization or mediating a dialogue with mucosa-associated immune cells. On the other hand, bifidobacteria induce the production of proteins in the intestine, by epithelial or immune cells, and other gut bacteria, which are key elements in orchestrating interactions among bifidobacteria, gut microbiota and host cells. This review aims to give a comprehensive overview on proteinaceous molecules described and characterized to date, as mediators of the dynamic interplay between bifidobacteria and the human host, providing a framework to identify knowledge gaps and future research needs.

  17. Defence mechanisms and immune evasion in the interplay between the humane immune system and Plasmodium falciparum

    DEFF Research Database (Denmark)

    Theander, T G

    1992-01-01

    Immunity to P. falciparum malaria is developed as a result of long term exposure to the parasite and depends on immunological memory. The key directors in immune recognition and regulation of the immunological responses are the T-cells. It seems reasonable to propose that immunity is acquired when...... with development of immunity. Several mechanisms seem to be operating. 1) Induction of the immune response to some macromolecules is avoided because the parasites are living inside host cells during part of their life cycle, and the reaction to other molecules is apparently avoided by mimicry of host molecules. 2...

  18. Innate immunity

    African Journals Online (AJOL)

    Ronnie Anderson is Director of the Medical Research Council Unit for Inflammation and Immunity. ... field have included macrophage, T cell, cytokine and cytokine activated killer cell interactions .... monocytes, mast cells, lymphocytes, eccrine.

  19. Immune system and melanoma biology: a balance between immunosurveillance and immune escape.

    Science.gov (United States)

    Passarelli, Anna; Mannavola, Francesco; Stucci, Luigia Stefania; Tucci, Marco; Silvestris, Francesco

    2017-12-01

    Melanoma is one of the most immunogenic tumors and its relationship with host immune system is currently under investigation. Many immunomodulatory mechanisms, favoring melanomagenesis and progression, have been described to interfere with the disablement of melanoma recognition and attack by immune cells resulting in immune resistance and immunosuppression. This knowledge produced therapeutic advantages, such as immunotherapy, aiming to overcome the immune evasion. Here, we review the current advances in cancer immunoediting and focus on melanoma immunology, which involves a dynamic interplay between melanoma and immune system, as well as on effects of "targeted therapies" on tumor microenvironment for combination strategies.

  20. Echinococcus multilocularis and Its Intermediate Host: A Model of Parasite-Host Interplay

    Directory of Open Access Journals (Sweden)

    Dominique Angèle Vuitton

    2010-01-01

    Full Text Available Host-parasite interactions in the E. multilocularis-intermediate host model depend on a subtle balance between cellular immunity, which is responsible for host's resistance towards the metacestode, the larval stage of the parasite, and tolerance induction and maintenance. The pathological features of alveolar echinococcosis. the disease caused by E. multilocularis, are related both to parasitic growth and to host's immune response, leading to fibrosis and necrosis, The disease spectrum is clearly dependent on the genetic background of the host as well as on acquired disturbances of Th1-related immunity. The laminated layer of the metacestode, and especially its carbohydrate components, plays a major role in tolerance induction. Th2-type and anti-inflammatory cytokines, IL-10 and TGF-β, as well as nitric oxide, are involved in the maintenance of tolerance and partial inhibition of cytotoxic mechanisms. Results of studies in the experimental mouse model and in patients suggest that immune modulation with cytokines, such as interferon-α, or with specific antigens could be used in the future to treat patients with alveolar echinococcosis and/or to prevent this very severe parasitic disease.

  1. Childhood immunization

    Science.gov (United States)

    Romain, Sandra; Schillaci, Michael A.

    2009-01-01

    ABSTRACT OBJECTIVE To examine childhood immunization levels relative to the number of family physicians, pediatricians, and public health nurses in Ontario. DESIGN Retrospective comparative analysis of publicly available data on immunization coverage levels and the relative number of family physicians, pediatricians, and public health nurses. SETTING Ontario. PARTICIPANTS Seven-year-old children, family physicians, pediatricians, and public health nurses in Ontario. MAIN OUTCOME MEASURES The association between immunization coverage levels and the relative number of family physicians, pediatricians, and public health nurses. RESULTS We found correlations between immunization coverage levels and the relative number (ie, per 1000 Ontario residents) of family physicians (ρ = 0.60) and pediatricians (ρ = 0.70) and a lower correlation with the relative number of public health nurses (ρ = 0.40), although none of these correlations was significant. A comparison of temporal trends illustrated that variation in the relative number of family physicians and pediatricians in Ontario was associated with similar variation in immunization coverage levels. CONCLUSION Increasing the number of family physicians and pediatricians might help to boost access to immunizations and perhaps other components of cost-saving childhood preventive care. PMID:19910599

  2. Dynamic intervention: pathogen disarmament of mitochondrial-based immune surveillance.

    Science.gov (United States)

    Holland, Robin L; Blanke, Steven R

    2014-11-12

    In this issue of Cell Host & Microbe, Suzuki et al. (2014) describe a Vibrio cholerae Type-III-secreted effector that targets mitochondrial dynamics to dampen host innate immune signaling. This suggests that mammalian hosts possess surveillance mechanisms to monitor pathogen-mediated alterations in the integrity of normal cellular processes and organelles. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Host defense, dendritic cells and the human lung

    NARCIS (Netherlands)

    J.M.W. van Haarst (Jan Maarten)

    1995-01-01

    textabstractHost defense mechanisms protect the body against microorganisms and other foreign structures. These mechanisms can be divided in nonspecific, or innate, and specific, or acquired, immunity. In both branches of immunity the several types of leukocytes (white blood cells) play a dominant

  4. Immune evasion in ebolavirus infections.

    Science.gov (United States)

    Audet, Jonathan; Kobinger, Gary P

    2015-02-01

    Ebola virus (EBOV) infects humans as well as several animal species. It can lead to a highly lethal disease, with mortality rates approaching 90% in primates. Recent advances have deepened our understanding of how this virus is able to prevent the development of protective immune responses. The EBOV genome encodes eight proteins, four of which were shown to interact with the host in ways that counteract the immune response. The viral protein 35 (VP35) is capable of capping dsRNA and interacts with IRF7 to prevent detection of the virus by immune cells. The main role of the soluble glycoprotein (sGP) is still unclear, but it is capable of subverting the anti-GP1,2 antibody response. The GP1,2 protein has shown anti-tetherin activity and the ability to hide cell-surface proteins. Finally, VP24 interferes with the production of interferons (IFNs) and with IFN signaling in infected cells. Taken together, these data point to extensive adaptation of EBOV to evade the immune system of dead end hosts. While our understanding of the interactions between the human and viral proteins increases, details of those interactions in other hosts remain largely unclear and represent a gap in our knowledge.

  5. Postoperative Complications of Beger Procedure

    Directory of Open Access Journals (Sweden)

    Nayana Samejima Peternelli

    2015-01-01

    Full Text Available Introduction. Chronic pancreatitis (CP is considered an inflammatory disease that may cause varying degrees of pancreatic dysfunction. Conservative and surgical treatment options are available depending on dysfunction severity. Presentation of Case. A 36-year-old male with history of heavy alcohol consumption and diagnosed CP underwent a duodenal-preserving pancreatic head resection (DPPHR or Beger procedure after conservative treatment failure. Refractory pain was reported on follow-up three months after surgery and postoperative imaging uncovered stones within the main pancreatic duct and intestinal dilation. The patient was subsequently subjected to another surgical procedure and intraoperative findings included protein plugs within the main pancreatic duct and pancreaticojejunal anastomosis stricture. A V-shaped enlargement and main pancreatic duct dilation in addition to the reconstruction of the previous pancreaticojejunal anastomosis were performed. The patient recovered with no further postoperative complications in the follow-up at an outpatient clinic. Discussion. Main duct and pancreaticojejunal strictures are an unusual complication of the Beger procedure but were identified intraoperatively as the cause of patient’s refractory pain and explained intraductal protein plugs accumulation. Conclusion. Patients that undergo Beger procedures should receive close outpatient clinical follow-up in order to guarantee postoperative conservative treatment success and therefore guarantee an early detection of postoperative complications.

  6. Postoperative ileus: a preventable event

    DEFF Research Database (Denmark)

    Holte, Kathrine; Kehlet, H

    2000-01-01

    BACKGROUND: Postoperative ileus has traditionally been accepted as a normal response to tissue injury. No data support any beneficial effect of ileus and indeed it may contribute to delayed recovery and prolonged hospital stay. Efforts should, therefore, be made to reduce such ileus. METHODS...

  7. Admission haematological abnormalities and postoperative ...

    African Journals Online (AJOL)

    Admission haematological abnormalities and postoperative outcomes in neonates with acute surgical conditions in Alexandria, Egypt. HL Wella, SMM Farahat. Abstract. No Abstract. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · AJOL African Journals ...

  8. The postoperative clinical outcomes and safety of early enteral nutrition in operated gastric cancer patients.

    Science.gov (United States)

    Li, Bing; Liu, Hong-Yi; Guo, Shao-Hua; Sun, Peng; Gong, Fang-Ming; Jia, Bao-Qing

    2015-01-01

    This study investigated the impact of early enteral nutrition (EEN) on the clinical outcomes of gastric cancer patients after radical gastrectomy. Four hundred gastric cancer patients undergoing radical gastrectomy of any extend with D2 nodal dissection were randomly divided into an experimental and a control group with 200 cases in each group. Patients in the control group received postoperative parenteral nutrition (PN), while patients in the experimental group received postoperative EEN. After treatment, the clinical outcomes, postoperative immune function, and nutritional status of the two groups were evaluated. The postoperative fever time, intestinal function recovery time, anal exhaust time, and the length of hospital stay for patients in the experimental group were significantly shorter than those of the control group. We did not find significant differences in anastomotic leak, postoperative ileus and regurgitation between the two groups. The activities of multiple immune cell types, including CD3⁺, CD4⁺, CD4⁺/CD8⁺, and natural killer (NK) cells, were significantly lower in both groups on postoperative day 1 when compared with the preoperative levels (p0.05). After treatment, levels of CD3⁺, CD4⁺, CD4⁺/CD8⁺, and NK cells in the experimental group patients were 35.6 ± 4.2, 42.2 ± 3.0, 1.7 ± 0.3, and 27.3 ± 5.3%, respectively, on postoperative day 7, which were similar to the preoperative levels. The immune cell levels from the control group patients remained significantly lower when compared with preoperative values; in addition, these values were also significantly lower when compared with the EEN patients (pgastric cancer patients undergoing radical gastrectomy, the clinical outcome, immune function and nutritional status after EEN were significantly improved. These data suggest the widespread use of EEN in clinical practice.

  9. Interaction of pathogens with host cholesterol metabolism.

    Science.gov (United States)

    Sviridov, Dmitri; Bukrinsky, Michael

    2014-10-01

    Pathogens of different taxa, from prions to protozoa, target cellular cholesterol metabolism to advance their own development and to impair host immune responses, but also causing metabolic complications, for example, atherosclerosis. This review describes recent findings of how pathogens do it. A common theme in interaction between pathogens and host cholesterol metabolism is pathogens targeting lipid rafts of the host plasma membrane. Many intracellular pathogens use rafts as an entry gate, taking advantage of the endocytic machinery and high abundance of outward-looking molecules that can be used as receptors. At the same time, disruption of the rafts' functional capacity, achieved by the pathogens through a number of various means, impairs the ability of the host to generate immune response, thus helping pathogen to thrive. Pathogens cannot synthesize cholesterol, and salvaging host cholesterol helps pathogens build advanced cholesterol-containing membranes and assembly platforms. Impact on cholesterol metabolism is not limited to the infected cells; proteins and microRNAs secreted by infected cells affect lipid metabolism systemically. Given an essential role that host cholesterol metabolism plays in pathogen development, targeting this interaction may be a viable strategy to fight infections, as well as metabolic complications of the infections.

  10. Postoperative mental confusion--association with postoperative hypoxemia

    DEFF Research Database (Denmark)

    Rosenberg, J; Kehlet, H

    1993-01-01

    under general anesthesia, were monitored for oxygen saturation (SpO2) with a pulse oximeter on a preoperative night and on the second night after operation (11:00 PM to 7:00 AM). All patients were tested with a mental test questionnaire (the Hodkinson modification of the original Roth-Hopkins test...... major surgery had decreased mental function on the third day (p operation, whereas minor surgery did not impair mental function. There was a significant correlation between mental function on the third day after operation and mean SpO2 on the second postoperative.......04). During stepwise multiple regression analysis in patients undergoing major surgery, a significant relationship was found between postoperative mental test score and SpO2 (p mental function and other perioperative variables (age, premedication dose, duration of operation...

  11. [Postoperative Chylotholax;Intraoperative Prevention and Postoperative Management].

    Science.gov (United States)

    Saito, Tomohito; Kariya, Shuji; Murakawa, Tomohiro

    2017-07-01

    Postoperative chylothorax is a relatively rare but potentially fatal complication caused by iatrogenic injury to thoracic duct system, with an incidence ranging from 2 to 4% after major lung surgery or esophagectomy. The pathophysiologic features of chylothorax include dehydration, loss of nutrients and immunological components. Intraopreative prevention is the first step for the management, and treatment options include conservative therapy, percutaneous intervention, and redo-operation. Although the treatment algorithm has not been standardized, chylothorax which is refractory to conservative treatment, or that with high output greater than 1,000 ml/day should be treated aggressively with thoracic duct embolization or redo-operation in a timely fashion. We herein review the anatomy and physiology of thoracic duct system and describe the overview of prevention and each theapeutic options of postoperative chylothorax.

  12. Postoperative diagnosis of the temporomandibular joint; Postoperative Kiefergelenkdiagnostik

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, S. [Universitaetsklinik fuer Radiodiagnostik, Vienna (Austria). Abt. fuer Osteologie; Undt, G. [Universitaetsklinik fuer Mund-, Kiefer- und Gesichtschirurgie, Vienna (Austria)

    2001-09-01

    Postoperative management of patients suffering from symptoms of the temporomandibular joint does not differ considerably from the one of preoperative examination protocols. Knowledge of previous surgery helps to plan patient work-up and to interpret normal postoperative findings (eminectomy, discectomy, susceptibility artefacts from metallic residues..) and typical complications (intraarticular loose bodies, dislocations, avascular necrosis, foreign body granulomatous reactions) appropriately. (orig.) [German] Wie auch in anderen Koerperregionen differiert das Diagnoseprotokoll von prae- und postoperativen Patienten mit Beschwerden des Kiefergelenks nicht wesentlich voneinander. Die Kenntnis des vorangegangenen Eingriffs hilft allerdings, die Untersuchung entsprechend zu planen und den Befund im Kontext richtig zu bewerten, um moegliche Komplikationen (intraartikulaere Fragmente, Dislokationen, avaskulaere Nekrose, Fremdkoerperreaktionen) und zu erwartende Befunde (Eminektomie, Diskektomie, Metallartefakte usw.) richtig zu interpretieren. (orig.)

  13. [Tuberculosis in compromised hosts].

    Science.gov (United States)

    2003-11-01

    Recent development of tuberculosis in Japan tends to converge on a specific high risk group. The proportion of tuberculosis developing particularly from the compromised hosts in the high risk group is especially high. At this symposium, therefore, we took up diabetes mellitus, gastrectomy, dialysis, AIDS and the elderly for discussion. Many new findings and useful reports for practical medical treatment are submitted; why these compromised hosts are predisposed to tuberculosis, tuberculosis diagnostic and remedial notes of those compromised hosts etc. It is an important question for the future to study how to prevent tuberculosis from these compromised hosts. 1. Tuberculosis in diabetes mellitus: aggravation and its immunological mechanism: Kazuyoshi KAWAKAMI (Department of Internal Medicine, Division of Infectious Diseases, Graduate School and Faculty of Medicine, University of the Ryukyus). It has been well documented that diabetes mellitus (DM) is a major aggravating factor in tuberculosis. The onset of this disease is more frequent in DM patients than in individuals with any underlying diseases. However, the precise mechanism of this finding remains to be fully understood. Earlier studies reported that the migration, phagocytosis and bactericidal activity of neutrophils are all impaired in DM patients, which is related to their reduced host defense to infection with extracellular bacteria, such as S. aureus and E. colli. Host defense to mycobacterial infection is largely mediated by cellular immunity, and Th1-related cytokines, such as IFN-gamma and IL-12, play a central role in this response. It is reported that serum level of these cytokines and their production by peripheral blood mononuclear cells (PBMC) are reduced in tuberculosis patients with DM, and this is supposed to be involved in the high incidence of tuberculosis in DM. Our study observed similar findings and furthermore indicated that IFN-gamma and IL-12 production by BCG-stimulated PBMC was lower

  14. Interplay between Candida albicans and the Mammalian Innate Host Defense

    Science.gov (United States)

    Cheng, Shih-Chin; Joosten, Leo A. B.; Kullberg, Bart-Jan

    2012-01-01

    Candida albicans is both the most common fungal commensal microorganism in healthy individuals and the major fungal pathogen causing high mortality in at-risk populations, especially immunocompromised patients. In this review, we summarize the interplay between the host innate system and C. albicans, ranging from how the host recognizes, responds, and clears C. albicans infection to how C. albicans evades, dampens, and escapes from host innate immunity. PMID:22252867

  15. Type 2 immunity and wound healing: evolutionary refinement of adaptive immunity by helminths

    Science.gov (United States)

    Gause, William C.; Wynn, Thomas A.; Allen, Judith E.

    2013-01-01

    Helminth-induced type 2 immune responses, which are characterized by the T helper 2 cell-associated cytokines interleukin-4 (IL-4) and IL-13, mediate host protection through enhanced tissue repair, the control of inflammation and worm expulsion. In this Opinion article, we consider type 2 immunity in the context of helminth-mediated tissue damage. We examine the relationship between the control of helminth infection and the mechanisms of wound repair, and we provide a new understanding of the adaptive type 2 immune response and its contribution to both host tolerance and resistance. PMID:23827958

  16. Regulation of intestinal homeostasis by innate immune cells.

    Science.gov (United States)

    Kayama, Hisako; Nishimura, Junichi; Takeda, Kiyoshi

    2013-12-01

    The intestinal immune system has an ability to distinguish between the microbiota and pathogenic bacteria, and then activate pro-inflammatory pathways against pathogens for host defense while remaining unresponsive to the microbiota and dietary antigens. In the intestine, abnormal activation of innate immunity causes development of several inflammatory disorders such as inflammatory bowel diseases (IBD). Thus, activity of innate immunity is finely regulated in the intestine. To date, multiple innate immune cells have been shown to maintain gut homeostasis by preventing inadequate adaptive immune responses in the murine intestine. Additionally, several innate immune subsets, which promote Th1 and Th17 responses and are implicated in the pathogenesis of IBD, have recently been identified in the human intestinal mucosa. The demonstration of both murine and human intestinal innate immune subsets contributing to regulation of adaptive immunity emphasizes the conserved innate immune functions across species and might promote development of the intestinal innate immunity-based clinical therapy.

  17. Postoperative imaging of paranasal sinuses

    International Nuclear Information System (INIS)

    Nemec, S.; Czerny, C.; Formanek, M.

    2007-01-01

    The radiological interpretation of postoperative changes of the paranasal sinuses requires knowledge of why and how the surgical intervention was performed and what the basic clinical findings were. It is important to know whether there was an inflammation, a reconstructive procedure, or a tumorous process. Multidetector computed tomography (MDCT) evaluated in a high-resolution bone window level setting represents the method of choice for imaging after nonfunctional and functional procedures after inflammatory changes as well as for imaging after reconstructive surgery because of facial trauma or before dental implantation. In the postoperative follow-up of tumor patients contrast-enhanced MDCT evaluated in a soft tissue window and bone window and especially magnetic resonance imaging (MRI) represent the standard. In many cases it is possible to differentiate tumor recurrence from inflammation with the help of contrast-enhanced multiplanar MRI and to detect bone marrow changes prior to CT. (orig.)

  18. Postoperative singultus: an osteopathic approach.

    Science.gov (United States)

    Petree, Kristie; Bruner, Jonathan

    2015-03-01

    Singultus, or hiccups, is a common medical condition. Despite exponential leaps in medicine, the pathophysiologic cause remains poorly defined. Persistent singultus has been associated with conditions such as pulmonary embolism and myocardial infarction. Singultus is also a well-known postoperative complication. The criterion standard of care for patients with singultus involves ruling out lethal pathologic causes, attempting physical stimulation with Valsava maneuvers or drinking water, and, if no relief has been achieved, administering drugs to ease the symptoms. The authors report a case of a man whose postoperative singultus was successfully managed with osteopathic manipulative treatment. This approach addresses many of the possible underlying neuromechanical causes of the aberrant reflex with minimal potential for adverse effects. Physicians should consider osteopathic manipulative treatment in the care of patients with singultus. © 2015 The American Osteopathic Association.

  19. Postoperative ileus: progress towards effective management

    DEFF Research Database (Denmark)

    Holte, Kathrine; Kehlet, Henrik

    2002-01-01

    The pathogenesis of postoperative ileus (PI) is multifactorial, and includes activation of inhibitory reflexes, inflammatory mediators and opioids (endogenous and exogenous). Accordingly, various strategies have been employed to prevent PI. As single-modality treatment, continuous postoperative e...

  20. Need for postoperative experience in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Corcione, S; Api, P; Magnoni, G

    1984-01-01

    A clinical evaluation regarding the efficacy of post-operative radiotherapy in 294 patients with breast cancer is presented. In the Author's opinion post-operative radiotherapy is fundamental in the treatment of this tumor. 21 refs.

  1. Management of pediatric postoperative chylothorax.

    Science.gov (United States)

    Bond, S J; Guzzetta, P C; Snyder, M L; Randolph, J G

    1993-09-01

    Questions persist about the management of postoperative chylothorax in infants and children. Our experience with postoperative chylothorax over the most recent decade (1980 to 1990) has been reviewed. The type and amount of drainage, data from cardiac catheterization and echocardiography, operative decisions and details, and eventual outcomes have been cataloged. All patients were initially treated with total gut rest, with operation reserved for unabated drainage. Chylothorax developed postoperatively in 15 infants and 11 children (18 with a cardiac procedure and 8 with a noncardiac procedure). The average age was 3.1 years. Spontaneous cessation and cure occurred in 19 (73.1%) of these 26 patients, with an average drainage duration of 11.9 days (range, 4 to 30 days). Those for whom operation was chosen drained preoperatively for an average of 29.2 days (range, 25 to 40 days). There were no deaths in either group. Complications were lymphopenia (2 patients) and fungal sepsis (1 patient). The amount of drainage per day was not significantly different between patients treated operatively and those treated nonoperatively. Failure of nonoperative management was associated with venous hypertension from increased right-sided cardiac pressures or central venous thrombosis (p < 0.05, Fisher's exact test). Presumably this increased pressure is transmitted to the lymphatic system. These patients should be identified early and considered for thoracic duct suture or pleuroperitoneal shunting.

  2. EARLY POSTOPERATIVE COMPLICATIONS AFTER RADICAL CYSTECTOMY

    Directory of Open Access Journals (Sweden)

    V. O. Mager

    2014-08-01

    Full Text Available Radical cystectomy (RCE is associated with a considerable number of early postoperative complications as before. Based on 10 years’ experience, this paper demonstrates the frequency (33.9 % and types of early complications following RCE, as well as postoperative mortality (5.5 % and its resulting causes. Although postoperative mortality is relatively low today, the frequency of early postoperative complications remains high as before.

  3. Immune System

    Science.gov (United States)

    ... of the Immune System Print en español El sistema inmunitario Whether you're stomping through the showers ... of Use Notice of Nondiscrimination Visit the Nemours Web site. Note: All information on TeensHealth® is for ...

  4. Immunizing Adults

    Centers for Disease Control (CDC) Podcasts

    Vaccines aren’t just for kids; adults also need to get immunized. Overall, far too many people 19 years and older aren’t getting the vaccines they need and remain unprotected. In this podcast, Dr. Walter Williams discuss the importance of adults being fully vaccinated.

  5. Assessing gene expression during pathogenesis: Use of qRT-PCR to follow toxin production in the entomopathogenic fungus Beauveria bassiana during infection and immune response of the insect host Triatoma infestans.

    Science.gov (United States)

    Lobo, Luciana S; Luz, Christian; Fernandes, Éverton K K; Juárez, M Patricia; Pedrini, Nicolás

    2015-06-01

    Entomopathogenic fungi secrete toxic secondary metabolites during the invasion of the insect hemocoel as part of the infection process. Although these compounds have been frequently mentioned as virulence factors, the roles of many of them remain poorly understood, including the question of whether they are expressed during the infection process. A major hurdle to this issue remains the low sensitivity of biochemical detection techniques (e.g., HPLC) within the complex samples that may contain trace quantities of fungal molecules inside the insect. In this study, quantitative reverse transcription real-time PCR (qRT-PCR) was used to measure the transcript levels within the insect fungal pathogen Beauveria bassiana, that encode for the synthetase enzymes of the secondary metabolites tenellin (BbtenS), beauvericin (BbbeaS) and bassianolide (BbbslS) during the infection of Triatoma infestans, a Chagas disease insect vector. Absolute quantification was performed at different time periods after insect treatment with various concentrations of propagules, either by immersing the insects in conidial suspensions or by injecting them with blastospores. Both BbtenS and BbbeaS were highly expressed in conidia-treated insects at days 3 and 12 post-treatment. In blastospore-injected insects, BbtenS and BbbeaS expression peaked at 24h post-injection and were also highly expressed in insect cadavers. The levels of BbbslS transcripts were much lower in all conditions tested. The expression patterns of insect genes encoding proteins that belong to the T. infestans humoral immune system were also evaluated with the same technique. This qPCR-based methodology can contribute to decifering the dynamics of entomopathogenic fungal infection at the molecular level. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Mucosal immunity to pathogenic intestinal bacteria.

    Science.gov (United States)

    Perez-Lopez, Araceli; Behnsen, Judith; Nuccio, Sean-Paul; Raffatellu, Manuela

    2016-03-01

    The intestinal mucosa is a particularly dynamic environment in which the host constantly interacts with trillions of commensal microorganisms, known as the microbiota, and periodically interacts with pathogens of diverse nature. In this Review, we discuss how mucosal immunity is controlled in response to enteric bacterial pathogens, with a focus on the species that cause morbidity and mortality in humans. We explain how the microbiota can shape the immune response to pathogenic bacteria, and we detail innate and adaptive immune mechanisms that drive protective immunity against these pathogens. The vast diversity of the microbiota, pathogens and immune responses encountered in the intestines precludes discussion of all of the relevant players in this Review. Instead, we aim to provide a representative overview of how the intestinal immune system responds to pathogenic bacteria.

  7. Evaluation and Comparison of the Pathogenicity and Host Immune Responses Induced by a G2b Taiwan Porcine Epidemic Diarrhea Virus (Strain Pintung 52) and Its Highly Cell-Culture Passaged Strain in Conventional 5-Week-Old Pigs.

    Science.gov (United States)

    Chang, Yen-Chen; Kao, Chi-Fei; Chang, Chia-Yu; Jeng, Chian-Ren; Tsai, Pei-Shiue; Pang, Victor Fei; Chiou, Hue-Ying; Peng, Ju-Yi; Cheng, Ivan-Chen; Chang, Hui-Wen

    2017-05-19

    A genogroup 2b (G2b) porcine epidemic diarrhea virus (PEDV) Taiwan Pintung 52 (PEDVPT) strain was isolated in 2014. The pathogenicity and host antibody responses elicited by low-passage (passage 5; PEDVPT-P5) and high-passage (passage 96; PEDVPT-P96) PEDVPT strains were compared in post-weaning PEDV-seronegative pigs by oral inoculation. PEDVPT-P5-inoculation induced typical diarrhea during 1-9 days post inoculation with fecal viral shedding persisting for 26 days. Compared to PEDVPT-P5, PEDVPT-P96 inoculation induced none-to-mild diarrhea and lower, delayed fecal viral shedding. Although PEDVPT-P96 elicited slightly lower neutralizing antibodies and PEDV-specific immunoglobulin G (IgG) and immunoglobulin A (IgA) titers, a reduction in pathogenicity and viral shedding of the subsequent challenge with PEDVPT-P5 were noted in both PEDVPT-P5- and PEDVPT-P96-inoculated pigs. Alignment and comparison of full-length sequences of PEDVPT-P5 and PEDVPT-P96 revealed 23 nucleotide changes and resultant 19 amino acid substitutions in non-structure proteins 2, 3, 4, 9, 14, 15, spike, open reading frame 3 (ORF3), and membrane proteins with no detectable deletion or insertion. The present study confirmed the pathogenicity of the PEDVPT isolate in conventional post-weaning pigs. Moreover, data regarding viral attenuation and potency of induced antibodies against PEDVPT-P5 identified PEDVPT-P96 as a potential live-attenuated vaccine candidate.

  8. Vaccines (immunizations) - overview

    Science.gov (United States)

    Vaccinations; Immunizations; Immunize; Vaccine shots; Prevention - vaccine ... of the vaccine. VACCINE SCHEDULE The recommended vaccination (immunization) schedule is updated every 12 months by the ...

  9. Cutaneous zygomycosis: A possible postoperative complication in immunocompetent individuals

    Directory of Open Access Journals (Sweden)

    Tilak Ragini

    2009-01-01

    Full Text Available Fungi in the class of zygomycetes usually produce serious infections in diabetics and immunocompromised hosts. Cutaneous zygomycosis is a less common form, with an unpredictable extent of anatomical involvement and clinical course. Here, we report two cases of primary cutaneous zygomycosis as postoperative complications in otherwise healthy females. Zygomycosis was suspected and specimens from the surgical debridement were examined by microbiological and histopathological studies for confirming the clinical diagnosis. Rapid diagnosis, liposomal amphotericin B, and proper debridement of affected tissue are necessary to avoid a fatal outcome.

  10. [Evasion of anti-infectious immunity by Brucella - A review].

    Science.gov (United States)

    Quan, Wurong; Yang, Yongjie

    2016-05-04

    Brucellosis, caused by Brucella species, is a worldwide zoonosis. As facultative intracellular pathogens, Brucella possess non-classical virulence factor, but its virulence is very powerful and can elicit chronic infections of both animals and humans. Evasion of host anti-infectious immunity is a prerequisite for chronic infections, this ability appears increasingly crucial for Brucella virulence. As successful pathogens, Brucella can escape or suppress innate immunity and modulate adaptive immunity to establish long lasting infections in host cells. In this review, we address the molecular mechanisms of Brucella to evade anti-infectious immunity. This will shed new insights on Brucella virulence and will, potentially, open new prophylactic avenues.

  11. Immune barriers of Ebola virus infection.

    Science.gov (United States)

    McElroy, Anita K; Mühlberger, Elke; Muñoz-Fontela, César

    2018-02-01

    Since its initial emergence in 1976 in northern Democratic Republic of Congo (DRC), Ebola virus (EBOV) has been a global health concern due to its virulence in humans, the mystery surrounding the identity of its host reservoir and the unpredictable nature of Ebola virus disease (EVD) outbreaks. Early after the first clinical descriptions of a disease resembling a 'septic-shock-like syndrome', with coagulation abnormalities and multi-system organ failure, researchers began to evaluate the role of the host immune response in EVD pathophysiology. In this review, we summarize how data gathered during the last 40 years in the laboratory as well as in the field have provided insight into EBOV immunity. From molecular mechanisms involved in EBOV recognition in infected cells, to antigen processing and adaptive immune responses, we discuss current knowledge on the main immune barriers of infection as well as outstanding research questions. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Mast cell activators as novel immune regulators.

    Science.gov (United States)

    Johnson-Weaver, Brandi; Choi, Hae Woong; Abraham, Soman N; Staats, Herman F

    2018-05-26

    Mast cells are an important cell type of the innate immune system that when activated, play a crucial role in generating protective innate host responses after bacterial and viral infection. Additionally, activated mast cells influence lymph node composition to regulate the induction of adaptive immune responses. The recognition that mast cells play a beneficial role in host responses to microbial infection and induction of adaptive immunity has provided the rationale to evaluate mast cell activators for use as antimicrobials or vaccine adjuvants. This review summarizes the role of mast cell activators in antimicrobial responses while also discussing the use of different classes of mast cell activators as potent vaccine adjuvants that enhance the induction of protective immune responses. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Feast or famine: the host-pathogen battle over amino acids.

    Science.gov (United States)

    Zhang, Yanjia J; Rubin, Eric J

    2013-07-01

    Intracellular bacterial pathogens often rely on their hosts for essential nutrients. Host cells, in turn, attempt to limit nutrient availability, using starvation as a mechanism of innate immunity. Here we discuss both host mechanisms of amino acid starvation and the diverse adaptations of pathogens to their nutrient-deprived environments. These processes provide both key insights into immune subversion and new targets for drug development. © 2013 John Wiley & Sons Ltd.

  14. Evolution of transgenerational immunity in invertebrates.

    Science.gov (United States)

    Pigeault, R; Garnier, R; Rivero, A; Gandon, S

    2016-09-28

    Over a decade ago, the discovery of transgenerational immunity in invertebrates shifted existing paradigms on the lack of sophistication of their immune system. Nonetheless, the prevalence of this trait and the ecological factors driving its evolution in invertebrates remain poorly understood. Here, we develop a theoretical host-parasite model and predict that long lifespan and low dispersal should promote the evolution of transgenerational immunity. We also predict that in species that produce both philopatric and dispersing individuals, it may pay to have a plastic allocation strategy with a higher transgenerational immunity investment in philopatric offspring because they are more likely to encounter locally adapted pathogens. We review all experimental studies published to date, comprising 21 invertebrate species in nine different orders, and we show that, as expected, longevity and dispersal correlate with the transfer of immunity to offspring. The validity of our prediction regarding the plasticity of investment in transgenerational immunity remains to be tested in invertebrates, but also in vertebrate species. We discuss the implications of our work for the study of the evolution of immunity, and we suggest further avenues of research to expand our knowledge of the impact of transgenerational immune protection in host-parasite interactions. © 2016 The Author(s).

  15. Innate Immune Responses in Leprosy

    Science.gov (United States)

    Pinheiro, Roberta Olmo; Schmitz, Veronica; Silva, Bruno Jorge de Andrade; Dias, André Alves; de Souza, Beatriz Junqueira; de Mattos Barbosa, Mayara Garcia; de Almeida Esquenazi, Danuza; Pessolani, Maria Cristina Vidal; Sarno, Euzenir Nunes

    2018-01-01

    Leprosy is an infectious disease that may present different clinical forms depending on host immune response to Mycobacterium leprae. Several studies have clarified the role of various T cell populations in leprosy; however, recent evidences suggest that local innate immune mechanisms are key determinants in driving the disease to its different clinical manifestations. Leprosy is an ideal model to study the immunoregulatory role of innate immune molecules and its interaction with nervous system, which can affect homeostasis and contribute to the development of inflammatory episodes during the course of the disease. Macrophages, dendritic cells, neutrophils, and keratinocytes are the major cell populations studied and the comprehension of the complex networking created by cytokine release, lipid and iron metabolism, as well as antimicrobial effector pathways might provide data that will help in the development of new strategies for leprosy management. PMID:29643852

  16. Humoral and cell-mediated immune responses in DNA immunized mink challenged with wild-type canine distemper virus.

    Science.gov (United States)

    Nielsen, Line; Søgaard, Mette; Karlskov-Mortensen, Peter; Jensen, Trine Hammer; Jensen, Tove Dannemann; Aasted, Bent; Blixenkrone-Møller, Merete

    2009-07-30

    The aim of the study was to investigate the different phases of the immune response after DNA immunization with the hemagglutinin and nucleoprotein genes from canine distemper virus (CDV). Although attenuated live CDV vaccines have effectively reduced the incidence of disease, canine distemper is still a problem worldwide. The broad host range of CDV creates a constant viral reservoir among wildlife animals. Our results demonstrated early humoral and cell-mediated immune responses (IFN-gamma) in DNA vaccinated mink compared to mock-vaccinated mink after challenge with a Danish wild-type CDV. The DNA vaccine-induced immunity protected the natural host against disease development.

  17. Balancing immune protection and immune pathology by CD8+ T cell responses to influenza infection

    Directory of Open Access Journals (Sweden)

    Susu eDuan

    2016-02-01

    Full Text Available Influenza A virus (IAV is a significant human pathogen causing annual epidemics and periodic pandemics. CD8+ cytotoxic T lymphocyte (CTL-mediated immunity contributes to clearance of virus-infected cells; CTL immunity targeting the conserved internal proteins of IAVs is a key protection mechanism when neutralizing antibodies are absent during heterosubtypic IAV infection. However, CTL infiltration into the airways, their cytotoxicity, and the effects of produced pro-inflammatory cytokines can cause severe lung tissue injury, thereby contributing to immunopathology. Studies have discovered complicated and exquisite stimulatory and inhibitory mechanisms that regulate CTL magnitude and effector activities during IAV infection. Here, we review the state of knowledge on the roles of IAV-specific CTLs in immune protection and immunopathology during IAV infection in animal models, highlighting the key findings of various requirements and constraints regulating the balance of immune protection and pathology involved in CTL immunity. We also discuss the evidence of cross-reactive CTL immunity as a positive correlate of cross-subtype protection during secondary IAV infection in both animal and human studies. We argue that the effects of CTL immunity on protection and immunopathology depend on multiple layers of host and viral factors, including complex host mechanisms to regulate CTL magnitude and effector activity, the pathogenic nature of the IAV, the innate response milieu, and the host historical immune context of influenza infection. Future efforts are needed to further understand these key host and viral factors, especially to differentiate those that constrain optimally effective CTL anti-viral immunity from those necessary to restrain CTL-mediated nonspecific immunopathology in the various contexts of IAV infection, in order to develop better vaccination and therapeutic strategies for modifying protective CTL immunity.

  18. Postoperative radiotherapy for intracranial meningioma

    International Nuclear Information System (INIS)

    Chun, Ha Chung; Lee, Myung Za

    2001-01-01

    To evaluate the effectiveness and tolerance of postoperative external radiotherapy for patients with intracranial meningiomas. The records of thirty three patients with intracranial meningiomas who were treated with postoperative external irradiation at our institution between Feb, 1988 and Nov, 1999 were retrospectively analyzed. Median age of patients at diagnosis was 53 years with range of 17 to 68 years. Sites of involvement were parasagital, cerebral convexity, sphenoid ridge, parasellar and tentorium cerebella. Of 33 evaluated patients, 15 transitional, 10 meningotheliomatous, 4 hemangiopericytic, 3 atypical and 1 malignant meningioma were identified. Four patients underwent biopsy alone and remaining 29 patients underwent total tumor resection. A dose of 50 to 60 Gy was delivered in 28-35 daily fractions over a period of 5 to 7 weeks. Follow-up period ranged from 12 months to 8 years. The actuarial survival rates at 5 and 7 years for entire group of patients were 78% and 67%, respectively. The corresponding disease free survival rates were 73% and 61 %, respectively. The overall local control rate at 5 years was 83%. One out of 25 patients in benign group developed local failure, while 4 out of 8 patients in malignant group did local failure (p <0.05), Of 4 patients who underwent biopsy alone, 2 developed local failure. There was no significant difference in 5 year actuarial survival between patients who underwent total tumor resection and those who did biopsy alone. Patients whose age is under 60 showed slightly better survival than those whose age is 60 or older, although this was not statistically significant. There was no documented late complications in any patients. Based on our study, we might conclude that postoperative external beam radiotherapy tends to improve survival of patients with intracranial meningiomas comparing with surgery alone

  19. Effects of posture on postoperative pulmonary function

    DEFF Research Database (Denmark)

    Nielsen, K G; Holte, Kathrine; Kehlet, H

    2003-01-01

    effect on postoperative pulmonary function in the sitting or standing position compared with the supine. Thus, avoidance of the supine position may improve postoperative pulmonary function. Three of six studies showed a positive effect on postoperative pulmonary function of the lateral side compared......BACKGROUND: Pulmonary morbidity is still a relevant complication to major surgery despite improvements in surgical technique and anaesthetic methods. Postoperative posture may be a pathogenic factor, but the effects of changes in postoperative posture on pulmonary function have not been reviewed...... with the supine. Thus, the lateral position has limited effects on pulmonary function. CONCLUSION: Changes of postoperative position from supine to sitting or standing are of major importance in the interpretation of postoperative pulmonary outcome studies and in future strategies to improve pulmonary outcome....

  20. Proteomic Characterization of Host Response to Yersinia pestis

    Energy Technology Data Exchange (ETDEWEB)

    Chromy, B; Perkins, J; Heidbrink, J; Gonzales, A; Murhpy, G; Fitch, J P; McCutchen-Maloney, S

    2004-05-11

    Host-pathogen interactions result in protein expression changes within both the host and the pathogen. Here, results from proteomic characterization of host response following exposure to Yersinia pestis, the causative agent of plague, and to two near neighbors, Y. pseudotuberculosis and Y. enterocolitica, are reported. Human monocyte-like cells were chosen as a model for macrophage immune response to pathogen exposure. Two-dimensional electrophoresis followed by mass spectrometry was used to identify host proteins with differential expression following exposure to these three closely related Yersinia species. This comparative proteomic characterization of host response clearly shows that host protein expression patterns are distinct for the different pathogen exposures, and contributes to further understanding of Y. pestis virulence and host defense mechanisms. This work also lays the foundation for future studies aimed at defining biomarkers for presymptomatic detection of plague.

  1. Adult Immunization

    Directory of Open Access Journals (Sweden)

    Omer Coskun

    2008-04-01

    Full Text Available Despite the many advances in modern medicine, each year thousands of people in the world die from diseases that are easily prevented by safe and effective vaccines. Few measures in preventive medicine are of such proven value and as easy to implement as routine immunization against infectious diseases. Prevention of infection by immunization is a lifelong process. There are a number of vaccines that all adults (¡I18 years require. There are also other vaccines that need to be tailored to meet individual variations in risk resulting from occupation, foreign travel, underlying illness, lifestyle and age. In this study, we tried to review this important subject. [TAF Prev Med Bull 2008; 7(2.000: 159-166

  2. Multimodal approach to postoperative recovery

    DEFF Research Database (Denmark)

    Kehlet, Henrik

    2009-01-01

    PURPOSE OF REVIEW: To provide updated information on recent developments within individual components of multimodal interventions to improve postoperative outcome (fast-track methodology). RECENT FINDINGS: The value of the fast-track methodology to improve recovery and decrease hospital stay...... and morbidity has been firmly consolidated, especially in colorectal procedures. An increasing amount of data from other procedures supports the value of the fast-track concept across procedures. Fast-track programs should be based on the analysis of procedure-specific factors that may influence outcome...

  3. Host response mechanisms in periodontal diseases

    Directory of Open Access Journals (Sweden)

    Nora SILVA

    2015-06-01

    a stage that presents a significantly host immune and inflammatory response to the microbial challenge that determine of susceptibility to develop the destructive/progressive periodontitis under the influence of multiple behavioral, environmental and genetic factors.

  4. Host response mechanisms in periodontal diseases

    Science.gov (United States)

    SILVA, Nora; ABUSLEME, Loreto; BRAVO, Denisse; DUTZAN, Nicolás; GARCIA-SESNICH, Jocelyn; VERNAL, Rolando; HERNÁNDEZ, Marcela; GAMONAL, Jorge

    2015-01-01

    presents a significantly host immune and inflammatory response to the microbial challenge that determine of susceptibility to develop the destructive/progressive periodontitis under the influence of multiple behavioral, environmental and genetic factors. PMID:26221929

  5. Immunizations for Preterm Babies

    Science.gov (United States)

    ... Issues Health Issues Health Issues Conditions Injuries & Emergencies Vaccine Preventable Diseases ... Children > Safety & Prevention > Immunizations > Immunizations For Preterm Babies Safety & ...

  6. Weakened Immune Systems

    Science.gov (United States)

    ... Issues Health Issues Health Issues Conditions Injuries & Emergencies Vaccine Preventable Diseases ... Children > Safety & Prevention > Immunizations > Weakened Immune Systems Safety & Prevention ...

  7. Immunizations: Active vs. Passive

    Science.gov (United States)

    ... Issues Health Issues Health Issues Conditions Injuries & Emergencies Vaccine Preventable Diseases ... Children > Safety & Prevention > Immunizations > Immunizations: Active vs. Passive Safety & ...

  8. Trichinella inflammatory myopathy: host or parasite strategy?

    Directory of Open Access Journals (Sweden)

    Chiumiento Lorena

    2011-03-01

    Full Text Available Abstract The parasitic nematode Trichinella has a special relation with muscle, because of its unique intracellular localization in the skeletal muscle cell, completely devoted in morphology and biochemistry to become the parasite protective niche, otherwise called the nurse cell. The long-lasting muscle infection of Trichinella exhibits a strong interplay with the host immune response, mainly characterized by a Th2 phenotype. The aim of this review is to illustrate the role of the Th2 host immune response at the muscle level during trichinellosis in different experimental models, such as knock-out or immuno-modulated mice. In particular, in knock-out mice a crucial role of IL-10 is evident for the regulation of inflammation intensity. The muscular host immune response to Trichinella is partially regulated by the intestinal phase of the parasite which emphasizes the intensity of the following muscle inflammation compared with animals infected by synchronized injections of newborn larvae. In eosinophil-ablated mice such as PHIL and GATA-- animals it was observed that there was an increased NOS2 expression in macrophages, driven by higher IFN-γ release, thus responsible for muscle larva damage. Besides modulation of the intestinal stage of the infection, using recombinant IL-12, increases the muscular parasite burden delaying adult worm expulsion from the intestine. Furthermore, a Th1 adjuvant of bacterial origin called Helicobacter pylori neutrophil activating protein (HP-NAP, administered during the intestinal phase of trichinellosis, alters the Th2 dependent response at muscle level. All these data from the literature delineate then a mutual adaptation between parasite and host immune response in order to achieve a strategic compromise between two evolutionary forces pointed towards the survival of both species.

  9. Hidden Consequences of Living in a Wormy World : Nematode-Induced Immune Suppression Facilitates Tuberculosis Invasion in African Buffalo

    NARCIS (Netherlands)

    Ezenwa, Vanessa O.; Etienne, Rampal S.; Luikart, Gordon; Beja-Pereira, Albano; Jolles, Anna E.

    2010-01-01

    Most hosts are infected with multiple parasites, and responses of the immune system to co occurring parasites may influence disease spread. Helminth infection can bias the host immune response toward a T-helper type 2 Th2) over a type 1 Th1) response, impairing the host's ability to control

  10. Postoperative Radiation Therapy of Craniopharyngioma

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Kyung Hwan; Kim, Il Han; Park, Charn Il; Cho, Byung Kyu [Seoul National University College of Medicine, Seoul (Korea, Republic of); Yun, Hyong Geln [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1993-06-15

    Between December 1979 and September 1989, 23 patients with craniopharyngioma who underwent surgery and postoperative radiation therapy were retrospectively evaluated to assess the efficacy of this management at the Department of Therapeutic Radiology, Seoul National University Hospital. Total removal of tumor was attempted in all patients. Of these, surgeons tried total removal in eight patients, but revealed residual mass by postoperative CT, and partial removal was done in 15 patients. The morphology of tumor on the operative finding was grouped into three types : cystic 13 (57%), solid 4 (17%), and mixed 6 (26%). Cystic type was predominant in {<=}20 years old group. Actuarial overall survival rates at 5 and 10 years were 95% and 81% respectively and actuarial tumor control rates were 74% and 50%. Surgical extent was not related to the survival rates(p=0.41). Pediatric and adolescent Patients(age of {<=}20 year) had a trend of better survival than that of adult patients(p=0.10). The results indicated that limited surgical excision followed by radiation therapy is recommended when total excision is not possible.

  11. Postoperative Radiation Therapy of Craniopharyngioma

    International Nuclear Information System (INIS)

    Shin, Kyung Hwan; Kim, Il Han; Park, Charn Il; Cho, Byung Kyu; Yun, Hyong Geln

    1993-01-01

    Between December 1979 and September 1989, 23 patients with craniopharyngioma who underwent surgery and postoperative radiation therapy were retrospectively evaluated to assess the efficacy of this management at the Department of Therapeutic Radiology, Seoul National University Hospital. Total removal of tumor was attempted in all patients. Of these, surgeons tried total removal in eight patients, but revealed residual mass by postoperative CT, and partial removal was done in 15 patients. The morphology of tumor on the operative finding was grouped into three types : cystic 13 (57%), solid 4 (17%), and mixed 6 (26%). Cystic type was predominant in ≤20 years old group. Actuarial overall survival rates at 5 and 10 years were 95% and 81% respectively and actuarial tumor control rates were 74% and 50%. Surgical extent was not related to the survival rates(p=0.41). Pediatric and adolescent Patients(age of ≤20 year) had a trend of better survival than that of adult patients(p=0.10). The results indicated that limited surgical excision followed by radiation therapy is recommended when total excision is not possible

  12. Viral (hepatitis C virus, hepatitis B virus, HIV) persistence and immune homeostasis

    Science.gov (United States)

    Zhou, Yun; Zhang, Ying; Moorman, Jonathan P; Yao, Zhi Q; Jia, Zhan S

    2014-01-01

    Immune homeostasis is a host characteristic that maintains biological balance within a host. Humans have evolved many host defence mechanisms that ensure the survival of individuals upon encountering a pathogenic infection, with recovery or persistence from a viral infection being determined by both viral factors and host immunity. Chronic viral infections, such as hepatitis B virus, hepatitis C virus and HIV, often result in chronic fluctuating viraemia in the face of host cellular and humoral immune responses, which are dysregulated by multi-faceted mechanisms that are incompletely understood. This review attempts to illuminate the mechanisms involved in this process, focusing on immune homeostasis in the setting of persistent viral infection from the aspects of host defence mechanism, including interferon-stimulated genes, apolipoprotein B mRNA editing enzyme catalytic polypeptide 3 (APOBEC3), autophagy and interactions of various immune cells, cytokines and regulatory molecules. PMID:24965611

  13. Host immune responses to nematodes: benefit or cost? Implications for future development of sustainable methods of control Resposta imune a nematódeos: vantagem ou custo? Implicações para o desenvolvimento futuro de métodos sustentáveis de controle

    Directory of Open Access Journals (Sweden)

    Andrew R. Sykes

    2010-07-01

    Full Text Available The nutritional and production costs associated with the development of a competent immune response against nematode parasites is described, based on data from sheep. Anorexia and changes in metabolism are considered to be driven by the host immune response itself and the question is raised about the wisdom of seeking to strengthen immune responses by genetic selection. Several phases of the immune response are identified with different implications for loss of productivity and opportunity for moderation of immune responses and production losses by nutrition. Many animals are able to manage nematode infections with little loss of productivity. In an era when attempts are being made to reduce anthelmintic use and create refugia to reduce the rate of development of drench resistance, treatments based on individual animal performance relative to production targets set by assessment of the prevailing nutritional environment will become more common. These developments, have already occurred in relation to the haematophagic nematodes, for example the "Famacha" technique. Computer-aided weighing and drafting has potential for use with the less pathogenic nematodes prevalent in temperate regions though we need to know more about the pathophysiology and nutritional costs of infections with Nematodirus spp.Os custos nutricionais e de produção associados ao desenvolvimento de uma resposta imune competente contra parasitas nematódeos estão descritos nesta revisão, com base em dados com ovinos. Anorexia e mudanças no metabolismo são consideradas o resultado da própria resposta imune do hospedeiro, e a questão é levantada quando se busca o fortalecimento da resposta imune pela seleção genética. Várias fases da resposta imune são identificadas com diferentes implicações, pela perda de produtividade e oportunidade para moderação da resposta imune e pela perda da produção pela nutrição. Muitos animais são capazes de lidar com as infec

  14. Association between elevated pre-operative glycosylated hemoglobin and post-operative infections after non-emergent surgery

    OpenAIRE

    Blankush, Joseph M.; Leitman, I. Michael; Soleiman, Aron; Tran, Trung

    2016-01-01

    Background: A chronic state of impaired glucose metabolism affects multiple components of the immune system, possibly leading to an increased incidence of post-operative infections. Such infections increase morbidity, length of stay, and overall cost. This study evaluates the correlation between elevated pre-operative glycosylated hemoglobin (HbA1c) and post-operative infections. Study design: Adult patients undergoing non-emergent procedures across all surgical subspecialties from January...

  15. Metabolites: messengers between the microbiota and the immune system.

    Science.gov (United States)

    Levy, Maayan; Thaiss, Christoph A; Elinav, Eran

    2016-07-15

    The mammalian intestine harbors one of the largest microbial densities on Earth, necessitating the implementation of control mechanisms by which the host evaluates the state of microbial colonization and reacts to deviations from homeostasis. While microbial recognition by the innate immune system has been firmly established as an efficient means by which the host evaluates microbial presence, recent work has uncovered a central role for bacterial metabolites in the orchestration of the host immune response. In this review, we highlight examples of how microbiota-modulated metabolites control the development, differentiation, and activity of the immune system and classify them into functional categories that illustrate the spectrum of ways by which microbial metabolites influence host physiology. A comprehensive understanding of how microbiota-derived metabolites shape the human immune system is critical for the rational design of therapies for microbiota-driven diseases. © 2016 Levy et al.; Published by Cold Spring Harbor Laboratory Press.

  16. Host-pathogen interplay of Haemophilus ducreyi.

    Science.gov (United States)

    Janowicz, Diane M; Li, Wei; Bauer, Margaret E

    2010-02-01

    Haemophilus ducreyi, the causative agent of the sexually transmitted infection chancroid, is primarily a pathogen of human skin. During infection, H. ducreyi thrives extracellularly in a milieu of professional phagocytes and other antibacterial components of the innate and adaptive immune responses. This review summarizes our understanding of the interplay between this pathogen and its host that leads to development and persistence of disease. H. ducreyi expresses key virulence mechanisms to resist host defenses. The secreted LspA proteins are tyrosine-phosphorylated by host kinases, which may contribute to their antiphagocytic effector function. The serum resistance and adherence functions of DsrA map to separate domains of this multifunctional virulence factor. An influx transporter protects H. ducreyi from killing by the antimicrobial peptide LL37. Regulatory genes have been identified that may coordinate virulence factor expression during disease. Dendritic cells and natural killer cells respond to H. ducreyi and may be involved in determining the differential outcomes of infection observed in humans. A human model of H. ducreyi infection has provided insights into virulence mechanisms that allow this human-specific pathogen to survive immune pressures. Components of the human innate immune system may also determine the ultimate fate of H. ducreyi infection by driving either clearance of the organism or an ineffective response that allows disease progression.

  17. Mechanism of immune evasion in breast cancer

    Science.gov (United States)

    Wang, Mozhi; Zhang, Changwang; Song, Yongxi; Wang, Zhenning; Wang, Yaojia; Luo, Fang; Xu, Yujie; Zhao, Yi; Wu, Zhonghua; Xu, Yingying

    2017-01-01

    Breast cancer (BC) is the most common malignant tumor among women, with high morbidity and mortality. Its onset, development, metastasis, and prognosis vary among individuals due to the interactions between tumors and host immunity. Many diverse mechanisms have been associated with BC, with immune evasion being the most widely studied to date. Tumor cells can escape from the body’s immune response, which targets abnormal components and foreign bodies, using different approaches including modification of surface antigens and modulation of the surrounding environment. In this review, we summarize the mechanisms and factors that impact the immunoediting process and analyze their functions in detail. PMID:28352189

  18. Adaptive Immunity to Cryptococcus neoformans Infections

    Directory of Open Access Journals (Sweden)

    Liliane Mukaremera

    2017-11-01

    Full Text Available The Cryptococcus neoformans/Cryptococcus gattii species complex is a group of fungal pathogens with different phenotypic and genotypic diversity that cause disease in immunocompromised patients as well as in healthy individuals. The immune response resulting from the interaction between Cryptococcus and the host immune system is a key determinant of the disease outcome. The species C. neoformans causes the majority of human infections, and therefore almost all immunological studies focused on C. neoformans infections. Thus, this review presents current understanding on the role of adaptive immunity during C. neoformans infections both in humans and in animal models of disease.

  19. Host control of human papillomavirus infection and disease.

    Science.gov (United States)

    Doorbar, John

    2018-02-01

    Most human papillomaviruses cause inapparent infections, subtly affecting epithelial homeostasis, to ensure genome persistence in the epithelial basal layer. As with conspicuous papillomas, these self-limiting lesions shed viral particles to ensure population level maintenance and depend on a balance between viral gene expression, immune cell stimulation and immune surveillance for persistence. The complex immune evasion strategies, characteristic of high-risk HPV types, also allow the deregulated viral gene expression that underlies neoplasia. Neoplasia occurs at particular epithelial sites where vulnerable cells such as the reserve or cuboidal cells of the cervical transformation zone are found. Beta papillomavirus infection can also predispose an individual with immune deficiencies to the development of cancers. The host control of HPV infections thus involves local interactions between keratinocytes and the adaptive immune response. Effective immune detection and surveillance limits overt disease, leading to HPV persistence as productive microlesions or in a true latent state. Copyright © 2017. Published by Elsevier Ltd.

  20. Use of Probiotics as Prophylaxis for Postoperative Infections

    Directory of Open Access Journals (Sweden)

    Peter Mangell

    2011-05-01

    Full Text Available Postoperative bacterial infections are common despite prophylactic administration of antibiotics. The wide-spread use of antibiotics in patients has contributed to the emergence of multiresistant bacteria. A restricted use of antibiotics must be followed in most clinical situations. In surgical patients there are several reasons for an altered microbial flora in the gut in combination with an altered barrier function leading to an enhanced inflammatory response to surgery. Several experimental and clinical studies have shown that probiotics (mainly lactobacilli may reduce the number of potentially pathogenia bacteria (PPM and restore a deranged barrier function. It is therefore of interest to test if these abilities of probiotics can be utilized in preoperative prophylaxis. These factors may be corrected by perioperative administration of probiotics in addition to antibiotics. Fourteen randomized clinical trials have been presented in which the effect of such regimens has been tested. It seems that in patients undergoing liver transplantation or elective surgery in the upper gastrointestinal tract prophylactic administration of different probiotic strains in combination with different fibers results in a three-fold reduction in postoperative infections. In parallel there seems to be a reduction in postoperative inflammation, although that has not been studied in a systematic way. The use of similar concepts in colorectal surgery has not been successful in reducing postoperative infections. Reasons for this difference are not obvious. It may be that higher doses of probiotics with longer duration are needed to influence microbiota in the lower gastrointestinal tract or that immune function in colorectal patients may not be as important as in transplantation or surgery in the upper gastrointestinal tract. The favorable results for the use of prophylactic probiotics in some settings warrant further controlled studies to elucidate potential

  1. Modulation of immune homeostasis by commensal bacteria

    Science.gov (United States)

    Ivanov, Ivaylo I.; Littman, Dan R.

    2011-01-01

    Intestinal bacteria form a resident community that has co-evolved with the mammalian host. In addition to playing important roles in digestion and harvesting energy, commensal bacteria are crucial for the proper functioning of mucosal immune defenses. Most of these functions have been attributed to the presence of large numbers of “innocuous” resident bacteria that dilute or occupy niches for intestinal pathogens or induce innate immune responses that sequester bacteria in the lumen, thus quenching excessive activation of the mucosal immune system. However it has recently become obvious that commensal bacteria are not simply beneficial bystanders, but are important modulators of intestinal immune homeostasis and that the composition of the microbiota is a major factor in pre-determining the type and robustness of mucosal immune responses. Here we review specific examples of individual members of the microbiota that modify innate and adaptive immune responses, and we focus on potential mechanisms by which such species-specific signals are generated and transmitted to the host immune system. PMID:21215684

  2. Salt, chloride, bleach, and innate host defense

    Science.gov (United States)

    Wang, Guoshun; Nauseef, William M.

    2015-01-01

    Salt provides 2 life-essential elements: sodium and chlorine. Chloride, the ionic form of chlorine, derived exclusively from dietary absorption and constituting the most abundant anion in the human body, plays critical roles in many vital physiologic functions, from fluid retention and secretion to osmotic maintenance and pH balance. However, an often overlooked role of chloride is its function in innate host defense against infection. Chloride serves as a substrate for the generation of the potent microbicide chlorine bleach by stimulated neutrophils and also contributes to regulation of ionic homeostasis for optimal antimicrobial activity within phagosomes. An inadequate supply of chloride to phagocytes and their phagosomes, such as in CF disease and other chloride channel disorders, severely compromises host defense against infection. We provide an overview of the roles that chloride plays in normal innate immunity, highlighting specific links between defective chloride channel function and failures in host defense. PMID:26048979

  3. Salt, chloride, bleach, and innate host defense.

    Science.gov (United States)

    Wang, Guoshun; Nauseef, William M

    2015-08-01

    Salt provides 2 life-essential elements: sodium and chlorine. Chloride, the ionic form of chlorine, derived exclusively from dietary absorption and constituting the most abundant anion in the human body, plays critical roles in many vital physiologic functions, from fluid retention and secretion to osmotic maintenance and pH balance. However, an often overlooked role of chloride is its function in innate host defense against infection. Chloride serves as a substrate for the generation of the potent microbicide chlorine bleach by stimulated neutrophils and also contributes to regulation of ionic homeostasis for optimal antimicrobial activity within phagosomes. An inadequate supply of chloride to phagocytes and their phagosomes, such as in CF disease and other chloride channel disorders, severely compromises host defense against infection. We provide an overview of the roles that chloride plays in normal innate immunity, highlighting specific links between defective chloride channel function and failures in host defense. © Society for Leukocyte Biology.

  4. Recent Advances in Aptamers Targeting Immune System.

    Science.gov (United States)

    Hu, Piao-Ping

    2017-02-01

    The immune system plays important role in protecting the organism by recognizing non-self molecules from pathogen such as bacteria, parasitic worms, and viruses. When the balance of the host defense system is disturbed, immunodeficiency, autoimmunity, and inflammation occur. Nucleic acid aptamers are short single-stranded DNA (ssDNA) or RNA ligands that interact with complementary molecules with high specificity and affinity. Aptamers that target the molecules involved in immune system to modulate their function have great potential to be explored as new diagnostic and therapeutic agents for immune disorders. This review summarizes recent advances in the development of aptamers targeting immune system. The selection of aptamers with superior chemical and biological characteristics will facilitate their application in the diagnosis and treatment of immune disorders.

  5. Postoperative interstitial radiotherapy of keloids

    International Nuclear Information System (INIS)

    Clavere, P.; Bonnafoux-Clavere, A.; Roullet, B.; Morzel, A.; Rhein, B.; Bonnetblanc, J.M.; Olivier, J.P.

    1993-01-01

    During an 8-year period, 21 patients with keloids (27 keloids) were treated with keloidectomy and post-operative interstitial radiotherapy by an iridium 192 wire. Only one patient had been previously treated by corticoids, without results. A dose of 12 Gy (three patients) to 15 Gy (18 patients) was delivered at a point 2.5 mm from the axis of the wire. The follow-up time was from 2 - 104 months. The success rate, at 7 months, was close to 88%. Ao recurrence occurred in three patients without relation to the method used, the lesion-age or the localization of the lesions. There were no side-effects. This method represents an effective, non-constraining and safe treatment for keloids if the contra-indications are respected

  6. Exploring the Homeostatic and Sensory Roles of the Immune System.

    Science.gov (United States)

    Marques, Rafael Elias; Marques, Pedro Elias; Guabiraba, Rodrigo; Teixeira, Mauro Martins

    2016-01-01

    Immunology developed under the notion of the immune system exists to fight pathogens. Recently, the discovery of interactions with commensal microbiota that are essential to human health initiated a change in this old paradigm. Here, we argue that the immune system has major physiological roles extending far beyond defending the host. Immune and inflammatory responses share the core property of sensing, defining the immune system also as a sensory system. The inference with the immune system collects, interprets, and stores information, while creating an identity of self, places it in close relationship to the nervous system, which suggests that these systems may have a profound evolutionary connection.

  7. A minimal model for multiple epidemics and immunity spreading.

    Directory of Open Access Journals (Sweden)

    Kim Sneppen

    Full Text Available Pathogens and parasites are ubiquitous in the living world, being limited only by availability of suitable hosts. The ability to transmit a particular disease depends on competing infections as well as on the status of host immunity. Multiple diseases compete for the same resource and their fate is coupled to each other. Such couplings have many facets, for example cross-immunization between related influenza strains, mutual inhibition by killing the host, or possible even a mutual catalytic effect if host immunity is impaired. We here introduce a minimal model for an unlimited number of unrelated pathogens whose interaction is simplified to simple mutual exclusion. The model incorporates an ongoing development of host immunity to past diseases, while leaving the system open for emergence of new diseases. The model exhibits a rich dynamical behavior with interacting infection waves, leaving broad trails of immunization in the host population. This obtained immunization pattern depends only on the system size and on the mutation rate that initiates new diseases.

  8. A minimal model for multiple epidemics and immunity spreading.

    Science.gov (United States)

    Sneppen, Kim; Trusina, Ala; Jensen, Mogens H; Bornholdt, Stefan

    2010-10-18

    Pathogens and parasites are ubiquitous in the living world, being limited only by availability of suitable hosts. The ability to transmit a particular disease depends on competing infections as well as on the status of host immunity. Multiple diseases compete for the same resource and their fate is coupled to each other. Such couplings have many facets, for example cross-immunization between related influenza strains, mutual inhibition by killing the host, or possible even a mutual catalytic effect if host immunity is impaired. We here introduce a minimal model for an unlimited number of unrelated pathogens whose interaction is simplified to simple mutual exclusion. The model incorporates an ongoing development of host immunity to past diseases, while leaving the system open for emergence of new diseases. The model exhibits a rich dynamical behavior with interacting infection waves, leaving broad trails of immunization in the host population. This obtained immunization pattern depends only on the system size and on the mutation rate that initiates new diseases.

  9. Salmonella Pathogenicity and Host Adaptation in Chicken-Associated Serovars

    Science.gov (United States)

    Johnson, Timothy J.; Ricke, Steven C.; Nayak, Rajesh; Danzeisen, Jessica

    2013-01-01

    SUMMARY Enteric pathogens such as Salmonella enterica cause significant morbidity and mortality. S. enterica serovars are a diverse group of pathogens that have evolved to survive in a wide range of environments and across multiple hosts. S. enterica serovars such as S. Typhi, S. Dublin, and S. Gallinarum have a restricted host range, in which they are typically associated with one or a few host species, while S. Enteritidis and S. Typhimurium have broad host ranges. This review examines how S. enterica has evolved through adaptation to different host environments, especially as related to the chicken host, and continues to be an important human pathogen. Several factors impact host range, and these include the acquisition of genes via horizontal gene transfer with plasmids, transposons, and phages, which can potentially expand host range, and the loss of genes or their function, which would reduce the range of hosts that the organism can infect. S. Gallinarum, with a limited host range, has a large number of pseudogenes in its genome compared to broader-host-range serovars. S. enterica serovars such as S. Kentucky and S. Heidelberg also often have plasmids that may help them colonize poultry more efficiently. The ability to colonize different hosts also involves interactions with the host's