Identification of Heme Oxygenase-1 as a Novel Predictor of Hematopoietic Stem Cell Transplantation Outcomes in Acute Leukemia

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Yinghao Lu

2016-09-01

Full Text Available Objective: The main aim of this study was to determine the correlation between clinical outcome and heme oxygenase-1 (HO-1 expression before and after hematopoietic stem cell transplantation (HSCT in acute leukemia. Methods: HO-1 mRNA levels in 83 patients were measured using qRT-PCR. In a comparative analysis of HO-1 levels in relation to different post-transplant outcomes, the HO-1 threshold, determined via the receiver operating characteristic (ROC curve, was effectively used to predict clinical relapse and acute graft-versus-host disease (aGVHD. The correlations among clinical relapse, aGVHD and HO-1 expression were analyzed based on this threshold. Results: Leukemia risk stratification and relative expression of HO-1 before pretreatment had significant effects on clinical relapse. Leukemia risk stratification, relative expression of HO-1 after HSCT and the interval from diagnosis to transplantation had a significant influence on aGVHD. Both relapse and aGVHD appeared to be associated with relative HO-1 expression. The relative expression rate of HO-1 was 1.131-1.186 before pretreatment, and strongly associated with post-transplantation relapse. The relative expression rate of HO-1 was 1.102-1.144 after transplantation, and closely related to aGVHD. ROC curve analysis revealed high specificity and sensitivity of HO-1 expression in predicting relapse and aGVHD after allo-HSCT. Conclusions: HO-1 expression can be effectively used as a predictor of relapse as well as a diagnostic factor of aGVHD after transplantation for allo-HSCT patients with acute leukemia.

Corruption of dendritic cell antigen presentation during acute GVHD leads to regulatory T-cell failure and chronic GVHD.

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Leveque-El Mouttie, Lucie; Koyama, Motoko; Le Texier, Laetitia; Markey, Kate A; Cheong, Melody; Kuns, Rachel D; Lineburg, Katie E; Teal, Bianca E; Alexander, Kylie A; Clouston, Andrew D; Blazar, Bruce R; Hill, Geoffrey R; MacDonald, Kelli P A

2016-08-11

Chronic graft-versus-host disease (cGVHD) is a major cause of late mortality following allogeneic bone marrow transplantation (BMT) and is characterized by tissue fibrosis manifesting as scleroderma and bronchiolitis obliterans. The development of acute GVHD (aGVHD) is a powerful clinical predictor of subsequent cGVHD, suggesting that aGVHD may invoke the immunologic pathways responsible for cGVHD. In preclinical models in which sclerodermatous cGVHD develops after a preceding period of mild aGVHD, we show that antigen presentation within major histocompatibility complex (MHC) class II of donor dendritic cells (DCs) is markedly impaired early after BMT. This is associated with a failure of regulatory T-cell (Treg) homeostasis and cGVHD. Donor DC-restricted deletion of MHC class II phenocopied this Treg deficiency and cGVHD. Moreover, specific depletion of donor Tregs after BMT also induced cGVHD, whereas adoptive transfer of Tregs ameliorated it. These data demonstrate that the defect in Treg homeostasis seen in cGVHD is a causative lesion and is downstream of defective antigen presentation within MHC class II that is induced by aGVHD. © 2016 by The American Society of Hematology.

Effective treatment of steroid and therapy-refractory acute graft-versus-host disease with a novel mesenchymal stromal cell product (MSC-FFM).

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Bader, Peter; Kuçi, Zyrafete; Bakhtiar, Shahrzad; Basu, Oliver; Bug, Gesine; Dennis, Michael; Greil, Johann; Barta, Aniko; Kállay, Krisztián M; Lang, Peter; Lucchini, Giovanna; Pol, Raj; Schulz, Ansgar; Sykora, Karl-Walter; von Luettichau, Irene; Herter-Sprie, Grit; Uddin, Mohammad Ashab; Jenkin, Phil; Alsultan, Abdulrahman; Buechner, Jochen; Stein, Jerry; Kelemen, Agnes; Jarisch, Andrea; Soerensen, Jan; Salzmann-Manrique, Emilia; Hutter, Martin; Schäfer, Richard; Seifried, Erhard; Klingebiel, Thomas; Bonig, Halvard; Kuçi, Selim

2018-01-29

The inability to generate mesenchymal stromal cells (MSCs) of consistent potency likely is responsible for inconsistent clinical outcomes of patients with aGvHD receiving MSC products. We developed a novel MSC manufacturing protocol characterized by high in vitro potency and near-identity of individual doses, referred to as "MSC-Frankfurt am Main (MSC-FFM)". Herein, we report outcomes of the 69 patients who have received MSC-FFM. These were 51 children and 18 adults with refractory aGvHD grade II (4%), III (36%) or IV (59%). Patients were refractory either to frontline therapy (steroids) (29%) or to steroids and 1-5 additional lines of immunosuppressants (71%) were given infusions in four weekly intervals. The day 28 overall response rate was 83%; at the last follow-up, 61% and 25% of patients were in complete or partial remission. The median follow-up was 8.1 months. Six-month estimate for cumulative incidence of non-relapse mortality was 27% (range, 16-38); leukemia relapse mortality was 2% (range, 0-5). This was associated with a superior six-month overall survival (OS) probability rate of 71% (range, 61-83), compared to the outcome of patients not treated with MSC-FFM. This novel product was effective in children and adults, suggesting that MSC-FFM represents a promising therapy for steroid refractory aGvHD.

Fulminant transfusion-associated graft-versus-host disease in a premature infant

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Berger, R.S.; Dixon, S.L.

1989-01-01

A fatal case of transfusion-associated graft-versus-host disease developed in a premature infant after receiving several blood products, including nonirradiated white blood cells. Transfusion-associated graft-versus-host disease can be prevented. Irradiation of blood products is the least controversial and most effective method. Treatment was unsuccessful in most reported cases of transfusion-associated graft-versus-host disease. Therefore irradiation of blood products before transfusing to patients susceptible to transfusion-associated graft-versus-host disease is strongly recommended

CD4+CD25highCD127low Regulatory T Cells in Peripheral Blood Are Not an Independent Factor for Chronic Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation

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Jolanta B. Perz

2012-01-01

Full Text Available Background. The therapeutic efficacy of allogeneic hemopoietic stem cell transplantation (HSCT largely relies on the graft-versus-leukemia (GVL effect. Uncontrolled graft-versus-host disease (GVHD is a feared complication of HSCT. Regulatory T cells (Treg are a subset of CD4+ T-helper cells believed to maintain tolerance after HSCT. It remains unclear whether low peripheral blood Treg have an impact on the risk for acute (aGVHD and chronic GVHD (cGVHD. Methods. In this paper we enumerated the CD4+CD25highCD127low Treg in the peripheral blood of 84 patients after at least 150 days from HSCT and in 20 healthy age-matched controls. Results. Although similar mean lymphocyte counts were found in patients and controls, CD3+CD4+ T-cell counts were significantly lower in patients. Patients also had significantly lower Treg percentages among lymphocytes as compared to controls. Patients with cGVHD had even higher percentages of Treg if compared to patients without cGVHD. In multivariate analysis, Treg percentages were not an independent factor for cGVHD. Conclusions. This paper did not show a relation between deficient peripheral blood Treg and cGVHD, therefore cGVHD does not seem to occur as a result of peripheral Treg paucity.

A randomized study of the prevention of acute graft-versus-host disease

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Ramsay, N.K.C.; Kersey, J.H.; Robison, L.L.; McGlave, P.B.; Woods, W.G.; Krivit, W.; Kim, T.H.; Goldman, A.I.; Nesbit, M.E. Jr.

1982-01-01

Acute graft-versus-host disease is a major problem in allogeneic bone-marrow transplantation. We performed a randomized study to compare the effectiveness of two regimens in the prevention of acute graft-versus-host disease. Thirty-five patients received methotrexate alone, and 32 received methotrexate, antithymocyte globulin, and prednisone. Of the patients who received methotrexate alone, 48 percent had acute graft-versus-host disease, as compared with 21 per cent of those who received methotrexate, antithymocyte globulin, and prednisone (P = 0.01). The age of the recipient was a significant factor in the development of acute graft-versus-host disease: Older patients had a higher incidence of the disease (P = 0.001). We conclude that the combination of methotrexate, antithymocyte globulin, and prednisone significantly decreased the incidence of acute graft-versus-host disease and should be used to prevent this disorder in patients receiving allogeneic marrow transplants

Pneumatosis intestinalis in children after allogeneic bone marrow transplantation

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Yeager, A M; Kanof, M E; Lake, A M; Kramer, S S; Jones, B; Saral, R; Santos, G W

1987-01-01

Four children, ages 3 to 8 years, developed pneumatosis intestinalis (PI) after allogeneic bone marrow transplantation (BMT) for acute leukemia or severe aplastic anemia. PI was detected at a median of 48 days (range, 10-63 days) after BMT and was associated with abdominal symptoms and clinical signs. All patients had severe systemic and/or highgrade cutaneous acute graft-versus-host disease (AGVHD) at some time after BMT and were receiving corticosteroids at the time of development of PI; however, PI was associated with concomitant severe AGVHD in only one patient. One patient with PI had Hafnia alvei bacteremia and another patient had gastroenteritis due to rotavirus and adenovirus. All patients were treated with supportive care and systemic broad-spectrum antibiotics, and PI resolved 2-16 days after onset. Two patients died with BMT-associated complications unrelated to PI. Multiple factors contribute to the development of PI after BMT, and the prognosis for recovery from PI is good with medical management alone. Overall survival in these patients is dependent on the frequency and severity of other conditions, such as AGVHD and opportunistic infections, after BMT.

Pneumatosis intestinalis in children after allogeneic bone marrow transplantation

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Yeager, A.M.; Kanof, M.E.; Lake, A.M.; Kramer, S.S.; Jones, B.; Saral, R.; Santos, G.W.

1987-01-01

Four children, ages 3 to 8 years, developed pneumatosis intestinalis (PI) after allogeneic bone marrow transplantation (BMT) for acute leukemia or severe aplastic anemia. PI was detected at a median of 48 days (range, 10-63 days) after BMT and was associated with abdominal symptoms and clinical signs. All patients had severe systemic and/or highgrade cutaneous acute graft-versus-host disease (AGVHD) at some time after BMT and were receiving corticosteroids at the time of development of PI; however, PI was associated with concomitant severe AGVHD in only one patient. One patient with PI had Hafnia alvei bacteremia and another patient had gastroenteritis due to rotavirus and adenovirus. All patients were treated with supportive care and systemic broad-spectrum antibiotics, and PI resolved 2-16 days after onset. Two patients died with BMT-associated complications unrelated to PI. Multiple factors contribute to the development of PI after BMT, and the prognosis for recovery from PI is good with medical management alone. Overall survival in these patients is dependent on the frequency and severity of other conditions, such as AGVHD and opportunistic infections, after BMT. (orig.)

Oral chronic graft-versus-host disease: analysis of dendritic cells subpopulations*

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Botari, Clara Marino Espricigo; Nunes, Adauto José Ferreira; de Souza, Mair Pedro; Orti-Raduan, Érica Sinara Lenharo; Salvio, Ana Gabriela

2014-01-01

The graft-versus-host disease is the major cause of morbidity and mortality in patients who have undergone hematopoietic stem cell transplantation. Aiming at contributing to the understanding of the role of myeloid and plasmacytoid dendritic cells, and natural killer cells in chronic graft-versus-host disease, we examined biopsies of jugal mucosa of 26 patients with acute myeloid leukemia who had undergone allogenic hematopoietic stem cell transplantation. Half of these patients developed oral chronic graft-versus-host disease. Microscopic sections were immunohistochemically stained for anti-CD1a, anti-CD123 and anti-CD56. We calculated the number of immunostained cells in the corium per square millimeter and applied the Mann-Whitney test. Results showed a statistically significant increase of myeloid dendritic cells (CD1a+; p=0,02) and natural killer cells (CD56; p=0,04) in patients with oral chronic graft-versus-host disease. CD123 immunostaining showed no statistical difference between groups. It was concluded that myeloid dendritic cells and natural killer cells participate in the development of oral chronic graft-versus-host disease. PMID:25054751

Oral chronic graft-versus-host disease: analysis of dendritic cells subpopulations.

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Botari, Clara Marino Espricigo; Nunes, Adauto José Ferreira; Souza, Mair Pedro de; Orti-Raduan, Erica Sinara Lenharo; Salvio, Ana Gabriela

2014-01-01

The graft-versus-host disease is the major cause of morbidity and mortality in patients who have undergone hematopoietic stem cell transplantation. Aiming at contributing to the understanding of the role of myeloid and plasmacytoid dendritic cells, and natural killer cells in chronic graft-versus-host disease, we examined biopsies of jugal mucosa of 26 patients with acute myeloid leukemia who had undergone allogenic hematopoietic stem cell transplantation. Half of these patients developed oral chronic graft-versus-host disease. Microscopic sections were immunohistochemically stained for anti-CD1a, anti-CD123 and anti-CD56. We calculated the number of immunostained cells in the corium per square millimeter and applied the Mann-Whitney test. Results showed a statistically significant increase of myeloid dendritic cells (CD1a+; p=0,02) and natural killer cells (CD56; p=0,04) in patients with oral chronic graft-versus-host disease. CD123 immunostaining showed no statistical difference between groups. It was concluded that myeloid dendritic cells and natural killer cells participate in the development of oral chronic graft-versus-host disease.

Host susceptibility hypothesis for shell disease in American lobsters.

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Tlusty, Michael F; Smolowitz, Roxanna M; Halvorson, Harlyn O; DeVito, Simone E

2007-12-01

Epizootic shell disease (ESD) in American lobsters Homarus americanus is the bacterial degradation of the carapace resulting in extensive irregular, deep erosions. The disease is having a major impact on the health and mortality of some American lobster populations, and its effects are being transferred to the economics of the fishery. While the onset and progression of ESD in American lobsters is undoubtedly multifactorial, there is little understanding of the direct causality of this disease. The host susceptibility hypothesis developed here states that although numerous environmental and pathological factors may vary around a lobster, it is eventually the lobster's internal state that is permissive to or shields it from the final onset of the diseased state. To support the host susceptibility hypothesis, we conceptualized a model of shell disease onset and severity to allow further research on shell disease to progress from a structured model. The model states that shell disease onset will occur when the net cuticle degradation (bacterial degradation, decrease of host immune response to bacteria, natural wear, and resorption) is greater than the net deposition (growth, maintenance, and inflammatory response) of the shell. Furthermore, lesion severity depends on the extent to which cuticle degradation exceeds deposition. This model is consistent with natural observations of shell disease in American lobster.

Marek’s disease herpesvirus vaccines integrate into chicken host chromosomes yet lack a virus-host phenotype associated with oncogenic transformation

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Marek's disease (MD) is a lymphotrophic and oncogenic disease of chickens that can lead to death in susceptible and unimmunized host birds. The causative pathogen, Marek's disease virus (MDV), a highly oncogenic alphaherpesvirus, integrates into host genome near the telomeres during viral latency an...

Ibrutinib Effective against Graft-Versus-Host Disease

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A Cancer Currents blog post on results from a small clinical trial showing that ibrutinib can effectively treat graft-versus-host-disease, a common and serious complication of allogeneic stem cell transplants.

Ecosystem screening approach for pathogen-associated microorganisms affecting host disease.

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Galiana, Eric; Marais, Antoine; Mura, Catherine; Industri, Benoît; Arbiol, Gilles; Ponchet, Michel

2011-09-01

The microbial community in which a pathogen evolves is fundamental to disease outcome. Species interacting with a pathogen on the host surface shape the distribution, density, and genetic diversity of the inoculum, but the role of these species is rarely determined. The screening method developed here can be used to characterize pathogen-associated species affecting disease. This strategy involves three steps: (i) constitution of the microbial community, using the pathogen as a trap; (ii) community selection, using extracts from the pathogen as the sole nutrient source; and (iii) molecular identification and the screening of isolates focusing on their effects on the growth of the pathogen in vitro and host disease. This approach was applied to a soilborne plant pathogen, Phytophthora parasitica, structured in a biofilm, for screening the microbial community from the rhizosphere of Nicotiana tabacum (the host). Two of the characterized eukaryotes interfered with the oomycete cycle and may affect the host disease. A Vorticella species acted through a mutualistic interaction with P. parasitica, disseminating pathogenic material by leaving the biofilm. A Phoma species established an amensal interaction with P. parasitica, strongly suppressing disease by inhibiting P. parasitica germination. This screening method is appropriate for all nonobligate pathogens. It allows the definition of microbial species as promoters or suppressors of a disease for a given biotope. It should also help to identify important microbial relationships for ecology and evolution of pathogens.

Low Body Mass Index Is Associated with Increased Risk of Acute GVHD after Umbilical Cord Blood Transplantation in Children and Young Adults with Acute Leukemia: A Study on Behalf of Eurocord and the EBMT Pediatric Disease Working Party.

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Paviglianiti, Annalisa; Dalle, Jean Hugues; Ayas, Mouhab; Boelens, Jan Jaap; Volt, Fernanda; Iori, Anna Paola; de Souza, Mair Pedro; Diaz, Miguel Angel; Michel, Gerard; Locatelli, Franco; Jubert, Charlotte; Yakoub-Agha, Ibrahim; Bittencourt, Henrique; Bertrand, Yves; Kenzey, Chantal; Tozatto Maio, Karina; Hayashi, Hiromi; Rocha, Vanderson; Bader, Peter; Gluckman, Eliane; Ruggeri, Annalisa

2018-04-01

Body mass index (BMI) may influence outcomes after allogeneic hematopoietic stem cell transplantation (HSCT). However, the impact of BMI on survival in children undergoing HSCT is not well defined, with conflicting results being reported on this issue. We analyzed 855 patients age 2 to 20 years with diagnosis of acute leukemia who underwent umbilical cord blood transplantation (UCBT) from 1990 to 2015. Patients were classified according to BMI as normal (fifth to 85th percentile), underweight (less than fifth percentile), overweight (85th to 95th percentile), and obese (>95th percentile) using growth charts for age and sex. All patients received single-unit UCBT after a myeloablative conditioning regimen. Diagnosis was acute lymphoblastic leukemia in 68% of the patients. Sixty-one percent of patients (n = 523) were in the normal BMI category, 11% (n = 96) were underweight, 16% (n = 137) overweight, and 12% (n = 99) obese. The cumulative incidence of grade II to IV acute graft-versus-host disease (aGVHD) was 35% (32% to 38%). According to pretransplantation BMI, aGVHD was 46% (33% to 59%) for underweight, 34% (31% to 42%) for normal, 36% (18% to 38%) for overweight, and 27% (15% to 37%) for obese (P = .04). In multivariate analysis, a BMI less than the fifth percentile was associated with higher incidence of acute grade II to IV GVHD compared with normal-BMI patients (hazard ratio,  1.61; 95% confidence interval, 1.15 to 2.26; P = .006). Our results show that being underweight at the time of transplantation is associated with an increased risk of aGVHD, highlighting the importance of nutritional status before UCBT. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Therapeutic regulatory T-cell adoptive transfer ameliorates established murine chronic GVHD in a CXCR5-dependent manner

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McDonald-Hyman, Cameron; Flynn, Ryan; Panoskaltsis-Mortari, Angela; Peterson, Nicholas; MacDonald, Kelli P. A.; Hill, Geoffrey R.; Luznik, Leo; Serody, Jonathan S.; Murphy, William J.; Maillard, Ivan; Munn, David H.; Turka, Laurence A.; Koreth, John; Cutler, Corey S.; Soiffer, Robert J.; Antin, Joseph H.; Ritz, Jerome

2016-01-01

Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation. In cGVHD, alloreactive T cells and germinal center (GC) B cells often participate in GC reactions to produce pathogenic antibodies. Although regulatory T cells (Tregs) can inhibit GC reactions, Treg numbers are reduced in cGVHD, contributing to cGVHD pathogenesis. Here, we explored 2 means to increase Tregs in cGVHD: interleukin-2/monoclonal antibody (IL-2/mAb) complexes and donor Treg infusions. IL-2/mAb complexes given over 1 month were efficacious in expanding Tregs and treating established cGVHD in a multi-organ-system disease mouse model characterized by GC reactions, antibody deposition, and lung dysfunction. In an acute GVHD (aGVHD) model, IL-2/mAb complexes given for only 4 days resulted in rapid mortality, indicating IL-2/mAb complexes can drive conventional T-cell (Tcon)-mediated injury. In contrast, Treg infusions, which uniformly suppress aGVHD, increased Treg frequency and were effective in preventing the onset of, and treating, established cGVHD. Efficacy was dependent upon CXCR5-sufficient Tregs homing to, and inhibiting, GC reactions. These studies indicate that the infusion of Tregs, especially ones enriched for GC homing, may be desirable for cGVHD therapy. Although IL-2/mAb complexes can be efficacious in cGVHD, a cautious approach needs to be taken in settings in which aGVHD elements, and associated Tcon, are present. PMID:27385791

Myeloablative radioimmunotherapy with 188Re-CD66mAb before stem cell transplantation. No increase of proinflammatory cytokine levels of TNF-α

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Mutschler, J.; Reske, S.N.; Steinbach, G.; Bunjes, D.; Buchmann, I.

2009-01-01

Tumour necrosis factor-α (TNF-α) serum levels may increase due to intensive conditioning regimes with high-dose chemotherapy and total body irradiation (TBI) before stem cell transplantation. This increases the risk for developing acute graft versus host disease (aGvHD) after stem cell transplantation. In this prospective study we investigated the influence of radioimmunotherapy with 188 Re-CD-66-mAb on changes on TNF-α serum levels. Patients, methods: In 18 patients we measured TNF-α before and up to 96 hours after radioimmunotherapy, in 2 patients in addition following TBI, in 9 patients also following chemotherapy. For measuring TNF-α we used an automated immunochemiluminescence assay (Immulite 1000 DPC Biermann, Bad Nauheim). The mean follow up period to record incidence of aGVHD was 100 days after stem cell transplantation. Compared to the basal levels before, the levels of TNF-α after conditioning with 188 Re-CD-66-mAb did not increase significantly and remained in the physiological range. In contrast, these initial physiological cytokine levels increased and became pathological following 48 h after total body irradiation (13.2 ± 6.6 pg/ml) and chemotherapy (10.8 ± 15.7 pg/ml). In our study we found a low incidence of aGvHD (22.2%, n = 4/18). Conclusion: These results demonstrate that additional conditioning therapy with 188 Re-CD-66-mAb does not increase proinflammatory cytokine levels of TNF-α. This finding may indicate that additive radioimmunotherapy may not be a significant factor for increasing the rate of conditioning- associated aGvHD. (orig.)

Reservoir-host amplification of disease impact in an endangered amphibian.

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Scheele, Ben C; Hunter, David A; Brannelly, Laura A; Skerratt, Lee F; Driscoll, Don A

2017-06-01

Emerging wildlife pathogens are an increasing threat to biodiversity. One of the most serious wildlife diseases is chytridiomycosis, caused by the fungal pathogen, Batrachochytrium dendrobatidis (Bd), which has been documented in over 500 amphibian species. Amphibians vary greatly in their susceptibility to Bd; some species tolerate infection, whereas others experience rapid mortality. Reservoir hosts-species that carry infection while maintaining high abundance but are rarely killed by disease-can increase extinction risk in highly susceptible, sympatric species. However, whether reservoir hosts amplify Bd in declining amphibian species has not been examined. We investigated the role of reservoir hosts in the decline of the threatened northern corroboree frog (Pseudophryne pengilleyi) in an amphibian community in southeastern Australia. In the laboratory, we characterized the response of a potential reservoir host, the (nondeclining) common eastern froglet (Crinia signifera), to Bd infection. In the field, we conducted frog abundance surveys and Bd sampling for both P. pengilleyi and C. signifera. We built multinomial logistic regression models to test whether Crinia signifera and environmental factors were associated with P. pengilleyi decline. C. signifera was a reservoir host for Bd. In the laboratory, many individuals maintained intense infections (>1000 zoospore equivalents) over 12 weeks without mortality, and 79% of individuals sampled in the wild also carried infections. The presence of C. signifera at a site was strongly associated with increased Bd prevalence in sympatric P. pengilleyi. Consistent with disease amplification by a reservoir host, P. pengilleyi declined at sites with high C. signifera abundance. Our results suggest that when reservoir hosts are present, population declines of susceptible species may continue long after the initial emergence of Bd, highlighting an urgent need to assess extinction risk in remnant populations of other declined

Haploidentical hematopoietic stem cell transplant with umbilical cord-derived multipotent mesenchymal cell infusion for the treatment of high-risk acute leukemia in children.

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Zhu, Ling; Wang, Zhidong; Zheng, Xiaoli; Ding, Li; Han, Dongmei; Yan, Hongmin; Guo, Zikuan; Wang, Hengxiang

2015-05-01

In this study, 25 children with high-risk acute leukemia received haploidentical hematopoietic stem cell transplant (haplo-HSCT) with co-transfusion of umbilical cord multipotent mesenchymal cells (UC-MSCs). Adverse effects, hematopoietic recovery, complications and outcome were observed during a median follow-up of 12.8 months (range: 3-25 months). Myeloid engraftment was rapid, and the median time to neutrophil and platelet recovery was 15.12 days and 20.08 days, respectively. Eight patients developed grade I skin acute graft-versus-host disease (aGVHD) that responded well to standard steroid therapy. Of note, cytomegalovirus viremia was observed in most patients (23/25 cases). Patients died mainly of leukemia relapse and pulmonary complication. Fourteen patients are currently alive and remain with full donor chimerism at the time of reporting. The present results suggest further clinical trials to testify the effectiveness of UC-MSCs to prevent aGVHD in haplo-HSCT for treating children with high-risk leukemia.

Search for alternate hosts of the coconut Cape Saint Paul Wilt Disease pathogen

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Yankey Egya Ndede

2009-03-01

Full Text Available Lethal Yellowing disease locally called Cape Saint Paul wilt disease (CSPWD is the bane of the coconut industry in Ghana and is caused by a phytoplasma. In Ghana, there are areas where the disease has re-infected re-plantings long after decimating all the palms in the area. This brings to the fore the possibility of alternate hosts in the spread of the disease because the pathogen is an obligate parasite. In this work, a number of plants were screened for their host status to the CSPWD pathogen. The presence of phytoplasmas in these plants was tested by polymerase chain reaction analysis using universal phytoplasma primers P1/P7 and CSPWD-specific primers G813/GAKSR. Although Desmodium adscendens tested positive to the CSPWD-specific primers, cloning and sequencing did not confirm it as an alternate host. The identification of alternate hosts will help us to evolve sound control strategies against the spread of the disease.

Host genetics of Epstein-Barr virus infection, latency and disease.

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Houldcroft, Charlotte J; Kellam, Paul

2015-03-01

Epstein-Barr virus (EBV) infects 95% of the adult population and is the cause of infectious mononucleosis. It is also associated with 1% of cancers worldwide, such as nasopharyngeal carcinoma, Hodgkin's lymphoma and Burkitt's lymphoma. Human and cancer genetic studies are now major forces determining gene variants associated with many cancers, including nasopharyngeal carcinoma and Hodgkin's lymphoma. Host genetics is also important in infectious disease; however, there have been no large-scale efforts towards understanding the contribution that human genetic variation plays in primary EBV infection and latency. This review covers 25 years of studies into host genetic susceptibility to EBV infection and disease, from candidate gene studies, to the first genome-wide association study of EBV antibody response, and an EBV-status stratified genome-wide association study of Hodgkin's lymphoma. Although many genes are implicated in EBV-related disease, studies are often small, not replicated or followed up in a different disease. Larger, appropriately powered genomic studies to understand the host response to EBV will be needed to move our understanding of the biology of EBV infection beyond the handful of genes currently identified. Fifty years since the discovery of EBV and its identification as a human oncogenic virus, a glimpse of the future is shown by the first whole-genome and whole-exome studies, revealing new human genes at the heart of the host-EBV interaction. © 2014 The Authors Reviews in Medical Virology published by John Wiley & Sons Ltd.

Homecare-based motor rehabilitation in musculoskeletal chronic graft versus host disease

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A Tendas

2011-01-01

Full Text Available Chronic graft versus host disease (cGVHD is a frequent complication of allogeneic stem cell transplantation. Extensive musculoskeletal and skin involvement may induce severe functional impairment, disability and quality of life deterioration. Physical rehabilitation is recommended as ancillary therapy in these forms, but experiences are sparse. A 39-year-old man affected by musculoskeletal and skin chronic graft versus host disease (cGVHD was treated with a homecare-based motor rehabilitation program during palliation for disease progression. Significant functional improvement was obtained. Motor rehabilitation should be strongly considered for patients with musculoskeletal cGVHD, both in the palliative and in the curative phase of disease.

Etanercept on steroid-refractary acute graft-versus-host disease

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Silvia González Munguía

2015-02-01

Full Text Available Objetive: To describe etanercept use and effectiveness on steroid- refractary acute graft-versus-host disease after hematopoietic cell transplantation. Method: Patients treated with etanercept as off label use for steroid-refractary acute graft-versus-host disease were selected and each patient’s medical history was reviewed to assess the clinical response. Results: The study included five patients: four presented with digestive manifestations and one presented pulmonary and liver manifestations. 80% of patients showed a clinical response: 60% a partial response and 20% a total response. In four cases etanercept 25mg was administered twice a week with variable duration of treatment, achieving no response in 1 case (3 weeks, partial response in two 2 cases (4 weeks and 8 weeks and a complete response in 1 case (8 week period. Only one case was treated with etanercept 50mg administered twice a week for 5 weeks with a partial treatment response. Conclusions: The clinical response rate is consistent with the previously published data. This updates the scarce bibliographic information about etanecept use in steroid-refractary acute graft-versus-host disease. Due to clinical design limitations and the small patient population, future clinical studies should be conducted to assess the efficacy and security of etanercept in these patients.

Infectious diseases of marine molluscs and host responses as revealed by genomic tools

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Ford, Susan E.

2016-01-01

More and more infectious diseases affect marine molluscs. Some diseases have impacted commercial species including MSX and Dermo of the eastern oyster, QPX of hard clams, withering syndrome of abalone and ostreid herpesvirus 1 (OsHV-1) infections of many molluscs. Although the exact transmission mechanisms are not well understood, human activities and associated environmental changes often correlate with increased disease prevalence. For instance, hatcheries and large-scale aquaculture create high host densities, which, along with increasing ocean temperature, might have contributed to OsHV-1 epizootics in scallops and oysters. A key to understanding linkages between the environment and disease is to understand how the environment affects the host immune system. Although we might be tempted to downplay the role of immunity in invertebrates, recent advances in genomics have provided insights into host and parasite genomes and revealed surprisingly sophisticated innate immune systems in molluscs. All major innate immune pathways are found in molluscs with many immune receptors, regulators and effectors expanded. The expanded gene families provide great diversity and complexity in innate immune response, which may be key to mollusc's defence against diverse pathogens in the absence of adaptive immunity. Further advances in host and parasite genomics should improve our understanding of genetic variation in parasite virulence and host disease resistance. PMID:26880838

Myeloablative radioimmunotherapy with {sup 188}Re-CD66mAb before stem cell transplantation. No increase of proinflammatory cytokine levels of TNF-{alpha}; Myeloablative Radioimmuntherapie mit {sup 188}Re-CD66mAb vor Stammzelltransplantation. Kein Anstieg proinflammatorischer Zytokinspiegel von TNF-{alpha}

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Mutschler, J.; Reske, S.N. [Universitaetsklinik Ulm (Germany). Klinik fuer Nuklearmedizin; Steinbach, G. [Universitaetsklinik Ulm (Germany). Abt. Klinische Chemie; Bunjes, D. [Universitaetsklinik Ulm (Germany). Medizinische Klinik III; Buchmann, I. [Universitaetsklinik Heidelberg (Germany). Abt. fuer Nuklearmedizin

2009-07-01

Tumour necrosis factor-{alpha} (TNF-{alpha}) serum levels may increase due to intensive conditioning regimes with high-dose chemotherapy and total body irradiation (TBI) before stem cell transplantation. This increases the risk for developing acute graft versus host disease (aGvHD) after stem cell transplantation. In this prospective study we investigated the influence of radioimmunotherapy with {sup 188}Re-CD-66-mAb on changes on TNF-{alpha} serum levels. Patients, methods: In 18 patients we measured TNF-{alpha} before and up to 96 hours after radioimmunotherapy, in 2 patients in addition following TBI, in 9 patients also following chemotherapy. For measuring TNF-{alpha} we used an automated immunochemiluminescence assay (Immulite 1000 DPC Biermann, Bad Nauheim). The mean follow up period to record incidence of aGVHD was 100 days after stem cell transplantation. Compared to the basal levels before, the levels of TNF-{alpha} after conditioning with {sup 188}Re-CD-66-mAb did not increase significantly and remained in the physiological range. In contrast, these initial physiological cytokine levels increased and became pathological following 48 h after total body irradiation (13.2 {+-} 6.6 pg/ml) and chemotherapy (10.8 {+-} 15.7 pg/ml). In our study we found a low incidence of aGvHD (22.2%, n = 4/18). Conclusion: These results demonstrate that additional conditioning therapy with {sup 188}Re-CD-66-mAb does not increase proinflammatory cytokine levels of TNF-{alpha}. This finding may indicate that additive radioimmunotherapy may not be a significant factor for increasing the rate of conditioning- associated aGvHD. (orig.)

Clinical impact of pre-transplant gut microbial diversity on outcomes of allogeneic hematopoietic stem cell transplantation.

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Doki, Noriko; Suyama, Masahiro; Sasajima, Satoshi; Ota, Junko; Igarashi, Aiko; Mimura, Iyo; Morita, Hidetoshi; Fujioka, Yuki; Sugiyama, Daisuke; Nishikawa, Hiroyoshi; Shimazu, Yutaka; Suda, Wataru; Takeshita, Kozue; Atarashi, Koji; Hattori, Masahira; Sato, Eiichi; Watakabe-Inamoto, Kyoko; Yoshioka, Kosuke; Najima, Yuho; Kobayashi, Takeshi; Kakihana, Kazuhiko; Takahashi, Naoto; Sakamaki, Hisashi; Honda, Kenya; Ohashi, Kazuteru

2017-09-01

Post-transplant microbial diversity in the gastrointestinal tract is closely associated with clinical outcomes following allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, little is known about the impact of the fecal microbiota before allo-HSCT. We analyzed fecal samples approximately 2 weeks before conditioning among 107 allo-HSCT recipients between 2013 and 2015. Microbial analysis was performed using 16S rRNA gene sequencing. Operational taxonomic unit-based microbial diversity was estimated by calculating the Shannon index. Patients were classified into three groups based on the diversity index: low (3) diversity (18 (16.8%), 48 (44.9%), and 41 (38.3%) patients, respectively). There were no significant differences in the 20-month overall survival, cumulative incidence of relapse, and non-relapse mortality among three groups. The cumulative incidence of grade II to IV acute graft-versus-host disease (aGVHD) was similar among the three groups (low 55.6%; intermediate 35.4%; high 48.8%, p = 0.339, at day 100). Furthermore, we found no differences in the cumulative incidence of grade II to IV acute gastrointestinal GVHD among the three groups (low 38.9%; intermediate 21.3%; high 24.4%, p = 0.778, at day 100). Regarding the composition of microbiota before allo-HSCT, aGVHD patients showed a significantly higher abundance of phylum Firmicutes (p strategy to prevent aGVHD.

Dynamics and Biocontrol: The Indirect Effects of a Predator Population on a Host-Vector Disease Model

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Fengyan Zhou

2014-01-01

Full Text Available A model of the interactions among a host population, an insect-vector population, which transmits virus from hosts to hosts, and a vector predator population is proposed based on virus-host, host-vector, and prey (vector-enemy theories. The model is investigated to explore the indirect effect of natural enemies on host-virus dynamics by reducing the vector densities, which shows the basic reproduction numbers R01 (without predators and R02 (with predators that provide threshold conditions on determining the uniform persistence and extinction of the disease in a host population. When the model is absent from predator, the disease is persistent if R01>1; in such a case, by introducing predators of a vector, then the insect-transmitted disease will be controlled if R02<1. From the point of biological control, these results show that an additional predator population of the vector may suppress the spread of vector-borne diseases. In addition, there exist limit cycles with persistence of the disease or without disease in presence of predators. Finally, numerical simulations are conducted to support analytical results.

Infusion-related febrile reaction after haploidentical stem cell transplantation in children is associated with higher rates of engraftment syndrome and acute graft-versus-host disease.

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Chen, Yao; Huang, Xiao-Jun; Liu, Kai-Yan; Chen, Huan; Chen, Yu-Hong; Zhang, Xiao-Hui; Wang, Feng-Rong; Han, Wei; Wang, Jing-Zhi; Wang, Yu; Yan, Chen-Hua; Zhang, Yuan-Yuan; Sun, Yu-Qian; Xu, Lan-Ping

2015-12-01

The clinical significance and prognostic impact of IRFR in pediatric recipients of haploidentical SCT are not clearly understood. Therefore, we attempted to determine how IRFR affects clinical outcomes in children. Clinical data from 100 consecutive pediatric patients (60 boys and 40 girls; median age, 12 yr [range, 2-18 yr] after haploidentical SCT between January 2010 and December 2012 were collected retrospectively. IRFR was described as unexplained fever (>38 °C) within 24 h after the infusion of haploidentical PBSCs. Thirty-eight (38.0%) cases met the criteria for IRFR. ES was found in 24 (63.2%) of the 38 children with IRFR, with the median time of developing ES of +9 (7-16) days, while only 15 (25.4%) of the 59 children without IRFR were found with ES (p children after haploidentical SCT. Thirty-eight children comprised the IRFR group, and 59 were in the control (non-IRFR) group. High incidence of ES was observed in children with the occurrence of IRFR. Similarly, the incidence of stage I-IV and II-IV aGVHD was significantly higher in the febrile group. Multivariate analysis showed IRFR to be the risk factor for ES and aGVHD. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Does canine inflammatory bowel disease influence gut microbial profile and host metabolism?

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Xu, Jia; Verbrugghe, Adronie; Louren?o, Marta; Janssens, Geert P. J.; Liu, Daisy J. X.; Van de Wiele, Tom; Eeckhaut, Venessa; Van Immerseel, Filip; Van de Maele, Isabel; Niu, Yufeng; Bosch, Guido; Junius, Greet; Wuyts, Brigitte; Hesta, Myriam

2016-01-01

Background Inflammatory bowel disease (IBD) refers to a diverse group of chronic gastrointestinal diseases, and gut microbial dysbiosis has been proposed as a modulating factor in its pathogenesis. Several studies have investigated the gut microbial ecology of dogs with IBD but it is yet unclear if this microbial profile can alter the nutrient metabolism of the host. The aim of the present study was to characterize the faecal bacterial profile and functionality as well as to determine host me...

Linking spring phenology with mechanistic models of host movement to predict disease transmission risk

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Merkle, Jerod A.; Cross, Paul C.; Scurlock, Brandon M.; Cole, Eric K.; Courtemanch, Alyson B.; Dewey, Sarah R.; Kauffman, Matthew J.

2018-01-01

Disease models typically focus on temporal dynamics of infection, while often neglecting environmental processes that determine host movement. In many systems, however, temporal disease dynamics may be slow compared to the scale at which environmental conditions alter host space-use and accelerate disease transmission.Using a mechanistic movement modelling approach, we made space-use predictions of a mobile host (elk [Cervus Canadensis] carrying the bacterial disease brucellosis) under environmental conditions that change daily and annually (e.g., plant phenology, snow depth), and we used these predictions to infer how spring phenology influences the risk of brucellosis transmission from elk (through aborted foetuses) to livestock in the Greater Yellowstone Ecosystem.Using data from 288 female elk monitored with GPS collars, we fit step selection functions (SSFs) during the spring abortion season and then implemented a master equation approach to translate SSFs into predictions of daily elk distribution for five plausible winter weather scenarios (from a heavy snow, to an extreme winter drought year). We predicted abortion events by combining elk distributions with empirical estimates of daily abortion rates, spatially varying elk seroprevelance and elk population counts.Our results reveal strong spatial variation in disease transmission risk at daily and annual scales that is strongly governed by variation in host movement in response to spring phenology. For example, in comparison with an average snow year, years with early snowmelt are predicted to have 64% of the abortions occurring on feedgrounds shift to occurring on mainly public lands, and to a lesser extent on private lands.Synthesis and applications. Linking mechanistic models of host movement with disease dynamics leads to a novel bridge between movement and disease ecology. Our analysis framework offers new avenues for predicting disease spread, while providing managers tools to proactively mitigate

Vulvovaginal Graft-Versus-Host Disease.

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Kornik, Rachel I; Rustagi, Alison S

2017-09-01

Vulvovaginal chronic graft-versus-host disease (cGVHD) is an underrecognized complication of stem cell transplantation. Early recognition may prevent severe sequelae. Genital involvement is associated with oral, ocular, and skin manifestations. Treatment includes topical immunosuppression, dilator use, and adjuvant topical estrogen. Clinical and histologic features may mimic other inflammatory vulvar conditions. In the right clinical context, these findings are diagnostic of chronic GVHD. Female recipients of allo-hematopoietic stem cell transplantation (HCT) are at higher risk of condylomas, cervical dysplasia, and neoplasia. The National Institutes of Health publishes guidelines for the diagnosis, grading, management, and supportive care for HCT patients by organ system. Copyright © 2017 Elsevier Inc. All rights reserved.

Integrated metagenomics/metaproteomics reveals human host-microbiota signatures of Crohn's disease.

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Alison R Erickson

Full Text Available Crohn's disease (CD is an inflammatory bowel disease of complex etiology, although dysbiosis of the gut microbiota has been implicated in chronic immune-mediated inflammation associated with CD. Here we combined shotgun metagenomic and metaproteomic approaches to identify potential functional signatures of CD in stool samples from six twin pairs that were either healthy, or that had CD in the ileum (ICD or colon (CCD. Integration of these omics approaches revealed several genes, proteins, and pathways that primarily differentiated ICD from healthy subjects, including depletion of many proteins in ICD. In addition, the ICD phenotype was associated with alterations in bacterial carbohydrate metabolism, bacterial-host interactions, as well as human host-secreted enzymes. This eco-systems biology approach underscores the link between the gut microbiota and functional alterations in the pathophysiology of Crohn's disease and aids in identification of novel diagnostic targets and disease specific biomarkers.

Integrated Metagenomics/Metaproteomics Reveals Human Host-Microbiota Signatures of Crohn's Disease

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Darzi, Youssef; Mongodin, Emmanuel F.; Pan, Chongle; Shah, Manesh; Halfvarson, Jonas; Tysk, Curt; Henrissat, Bernard; Raes, Jeroen; Verberkmoes, Nathan C.; Jansson, Janet K.

2012-01-01

Crohn's disease (CD) is an inflammatory bowel disease of complex etiology, although dysbiosis of the gut microbiota has been implicated in chronic immune-mediated inflammation associated with CD. Here we combined shotgun metagenomic and metaproteomic approaches to identify potential functional signatures of CD in stool samples from six twin pairs that were either healthy, or that had CD in the ileum (ICD) or colon (CCD). Integration of these omics approaches revealed several genes, proteins, and pathways that primarily differentiated ICD from healthy subjects, including depletion of many proteins in ICD. In addition, the ICD phenotype was associated with alterations in bacterial carbohydrate metabolism, bacterial-host interactions, as well as human host-secreted enzymes. This eco-systems biology approach underscores the link between the gut microbiota and functional alterations in the pathophysiology of Crohn's disease and aids in identification of novel diagnostic targets and disease specific biomarkers. PMID:23209564

Early and late oral features of chronic graft-versus-host disease

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Alessandra Oliveira Ferrari Gomes

2014-01-01

Full Text Available Background: Chronic graft-versus-host disease is a serious complication of allogeneic hematopoietic cell transplantation, and the mouth is one of the affected sites. Objective: The aim of this study was to evaluate the oral features of this disease after hematopoietic cell transplantation. Methods: This was a cross-sectional multicenter study that enrolled patients submitted to transplantation. Oral evaluations used the National Institutes of Health criteria, salivary flow rates, and the range of mouth opening. Pain and xerostomia were evaluated through a visual analogue scale. Patients were divided into two groups based on the transplantation time (up to one year and more than one year. Results: Of the 57 evaluated recipients, 44 had chronic graft-versus-host disease: ten (22.72% in the group with less than one year after transplantation, and 34 (77.27% in the group with more than one year after transplantation. Lichenoid/hyperkeratotic plaques, erythematous lesions, xerostomia, and hyposalivation were the most commonly reported oral features. Lichenoid/hyperkeratotic plaques were significantly more common in patients within the first year after the transplant. The labial mucosa was affected more in the first year. No significant changes occurred in the frequency of xerostomia, hyposalivation, and reduced mouth opening regarding time after transplantation. Conclusion: Oral chronic graft-versus-host disease lesions were identified early in the course of the disease. The changes observed in salivary gland function and in the range of mouth opening were not correlated with the time after transplantation.

Emerging fungal diseases: the importance of the host.

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Procop, Gary W; Roberts, Glenn D

2004-09-01

More yeasts and molds are now recognized to cause more human disease than ever before. This development is not due to a change in the virulence of these fungi, but rather to changes in the human host. These changes include immunosuppression secondary to the pandemic of HIV, the use of life-saving advances in chemotherapy and organ transplantation, and the use of corticosteroids and other immunosuppressive agents to treat a variety of diseases. Fungi that were once considered common saprophytes are now recognized as potential pathogens in these patients. This situation necessitates better communication than ever between the clinician, pathologist, and clinical mycologist to ensure the prompt and accurate determination of the cause of fungal diseases.

Host behaviour–parasite feedback: an essential link between animal behaviour and disease ecology

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Archie, Elizabeth A.; Craft, Meggan E.; Hawley, Dana M.; Martin, Lynn B.; Moore, Janice; White, Lauren

2016-01-01

Animal behaviour and the ecology and evolution of parasites are inextricably linked. For this reason, animal behaviourists and disease ecologists have been interested in the intersection of their respective fields for decades. Despite this interest, most research at the behaviour–disease interface focuses either on how host behaviour affects parasites or how parasites affect behaviour, with little overlap between the two. Yet, the majority of interactions between hosts and parasites are probably reciprocal, such that host behaviour feeds back on parasites and vice versa. Explicitly considering these feedbacks is essential for understanding the complex connections between animal behaviour and parasite ecology and evolution. To illustrate this point, we discuss how host behaviour–parasite feedbacks might operate and explore the consequences of feedback for studies of animal behaviour and parasites. For example, ignoring the feedback of host social structure on parasite dynamics can limit the accuracy of predictions about parasite spread. Likewise, considering feedback in studies of parasites and animal personalities may provide unique insight about the maintenance of variation in personality types. Finally, applying the feedback concept to links between host behaviour and beneficial, rather than pathogenic, microbes may shed new light on transitions between mutualism and parasitism. More generally, accounting for host behaviour–parasite feedbacks can help identify critical gaps in our understanding of how key host behaviours and parasite traits evolve and are maintained. PMID:27053751

Host behaviour-parasite feedback: an essential link between animal behaviour and disease ecology.

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Ezenwa, Vanessa O; Archie, Elizabeth A; Craft, Meggan E; Hawley, Dana M; Martin, Lynn B; Moore, Janice; White, Lauren

2016-04-13

Animal behaviour and the ecology and evolution of parasites are inextricably linked. For this reason, animal behaviourists and disease ecologists have been interested in the intersection of their respective fields for decades. Despite this interest, most research at the behaviour-disease interface focuses either on how host behaviour affects parasites or how parasites affect behaviour, with little overlap between the two. Yet, the majority of interactions between hosts and parasites are probably reciprocal, such that host behaviour feeds back on parasites and vice versa. Explicitly considering these feedbacks is essential for understanding the complex connections between animal behaviour and parasite ecology and evolution. To illustrate this point, we discuss how host behaviour-parasite feedbacks might operate and explore the consequences of feedback for studies of animal behaviour and parasites. For example, ignoring the feedback of host social structure on parasite dynamics can limit the accuracy of predictions about parasite spread. Likewise, considering feedback in studies of parasites and animal personalities may provide unique insight about the maintenance of variation in personality types. Finally, applying the feedback concept to links between host behaviour and beneficial, rather than pathogenic, microbes may shed new light on transitions between mutualism and parasitism. More generally, accounting for host behaviour-parasite feedbacks can help identify critical gaps in our understanding of how key host behaviours and parasite traits evolve and are maintained. © 2016 The Author(s).

Survival relative to new and ancestral host plants, phytoplasma infection, and genetic constitution in host races of a polyphagous insect disease vector

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Maixner, Michael; Albert, Andreas; Johannesen, Jes

2014-01-01

Dissemination of vectorborne diseases depends strongly on the vector's host range and the pathogen's reservoir range. Because vectors interact with pathogens, the direction and strength of a vector's host shift is vital for understanding epidemiology and is embedded in the framework of ecological specialization. This study investigates survival in host-race evolution of a polyphagous insect disease vector, Hyalesthes obsoletus, whether survival is related to the direction of the host shift (from field bindweed to stinging nettle), the interaction with plant-specific strains of obligate vectored pathogens/symbionts (stolbur phytoplasma), and whether survival is related to genetic differentiation between the host races. We used a twice repeated, identical nested experimental design to study survival of the vector on alternative hosts and relative to infection status. Survival was tested with Kaplan–Meier analyses, while genetic differentiation between vector populations was quantified with microsatellite allele frequencies. We found significant direct effects of host plant (reduced survival on wrong hosts) and sex (males survive longer than females) in both host races and relative effects of host (nettle animals more affected than bindweed animals) and sex (males more affected than females). Survival of bindweed animals was significantly higher on symptomatic than nonsymptomatic field bindweed, but in the second experiment only. Infection potentially had a positive effect on survival in nettle animals but due to low infection rates the results remain suggestive. Genetic differentiation was not related to survival. Greater negative plant-transfer effect but no negative effect of stolbur in the derived host race suggests preadaptation to the new pathogen/symbiont strain before strong diversifying selection during the specialization process. Physiological maladaptation or failure to accept the ancestral plant will have similar consequences, namely positive assortative

Molecular Mechanisms of Foot-and-Mouth Disease Virus Targeting the Host Antiviral Response.

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Rodríguez Pulido, Miguel; Sáiz, Margarita

2017-01-01

Foot-and-mouth disease virus (FMDV) is the causative agent of an acute vesicular disease affecting pigs, cattle and other domestic, and wild animals worldwide. The aim of the host interferon (IFN) response is to limit viral replication and spread. Detection of the viral genome and products by specialized cellular sensors initiates a signaling cascade that leads to a rapid antiviral response involving the secretion of type I- and type III-IFNs and other antiviral cytokines with antiproliferative and immunomodulatory functions. During co-evolution with their hosts, viruses have acquired strategies to actively counteract host antiviral responses and the balance between innate response and viral antagonism may determine the outcome of disease and pathogenesis. FMDV proteases Lpro and 3C have been found to antagonize the host IFN response by a repertoire of mechanisms. Moreover, the putative role of other viral proteins in IFN antagonism is being recently unveiled, uncovering sophisticated immune evasion strategies different to those reported to date for other members of the Picornaviridae family. Here, we review the interplay between antiviral responses induced by FMDV infection and viral countermeasures to block them. Research on strategies used by viruses to modulate immunity will provide insights into the function of host pathways involved in defense against pathogens and will also lead to development of new therapeutic strategies to fight virus infections.

Transfusion-associated graft-versus-host disease

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Rappeport, J.M.

1990-01-01

The clinical pathologic syndrome of graft-versus-host disease (GVHD) is usually a sequela of bone marrow transplantation. This disorder occurs as a result of recognition by engrafted donor-derived lymphocytes of foreign recipient transplantation antigens. GVHD may also result from engraftment of lymphocytes from other sources, including (1) transfusion of lymphocytes containing blood components, (2) transplacental maternal fetal transfusion, and (3) passive transfer of lymphocytes in solid organ transplantation. The recipients are usually severely immunodeficient and thus incapable of rejecting the transfused lymphocytes. This syndrome may, however, also develop in immunologically competent patients receiving blood products from individuals with histocompatibility antigens not recognized as foreign. 58 refs

MODELING HOST-PATHOGEN INTERACTIONS: COMPUTATIONAL BIOLOGY AND BIOINFORMATICS FOR INFECTIOUS DISEASE RESEARCH (Session introduction)

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McDermott, Jason E.; Braun, Pascal; Bonneau, Richard A.; Hyduke, Daniel R.

2011-12-01

Pathogenic infections are a major cause of both human disease and loss of crop yields and animal stocks and thus cause immense damage to the worldwide economy. The significance of infectious diseases is expected to increase in an ever more connected warming world, in which new viral, bacterial and fungal pathogens can find novel hosts and ecologic niches. At the same time, the complex and sophisticated mechanisms by which diverse pathogenic agents evade defense mechanisms and subvert their hosts networks to suit their lifestyle needs is still very incompletely understood especially from a systems perspective [1]. Thus, understanding host-pathogen interactions is both an important and a scientifically fascinating topic. Recently, technology has offered the opportunity to investigate host-pathogen interactions on a level of detail and scope that offers immense computational and analytical possibilities. Genome sequencing was pioneered on some of these pathogens, and the number of strains and variants of pathogens sequenced to date vastly outnumbers the number of host genomes available. At the same time, for both plant and human hosts more and more data on population level genomic variation becomes available and offers a rich field for analysis into the genetic interactions between host and pathogen.

Host Phylogeny Determines Viral Persistence and Replication in Novel Hosts

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Longdon, Ben; Hadfield, Jarrod D.; Webster, Claire L.

2011-01-01

Pathogens switching to new hosts can result in the emergence of new infectious diseases, and determining which species are likely to be sources of such host shifts is essential to understanding disease threats to both humans and wildlife. However, the factors that determine whether a pathogen can infect a novel host are poorly understood. We have examined the ability of three host-specific RNA-viruses (Drosophila sigma viruses from the family Rhabdoviridae) to persist and replicate in 51 different species of Drosophilidae. Using a novel analytical approach we found that the host phylogeny could explain most of the variation in viral replication and persistence between different host species. This effect is partly driven by viruses reaching a higher titre in those novel hosts most closely related to the original host. However, there is also a strong effect of host phylogeny that is independent of the distance from the original host, with viral titres being similar in groups of related hosts. Most of this effect could be explained by variation in general susceptibility to all three sigma viruses, as there is a strong phylogenetic correlation in the titres of the three viruses. These results suggest that the source of new emerging diseases may often be predictable from the host phylogeny, but that the effect may be more complex than simply causing most host shifts to occur between closely related hosts. PMID:21966271

Angiostrongylus spp. in the Americas: geographical and chronological distribution of definitive hosts versus disease reports.

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Valente, Romina; Robles, Maria Del Rosario; Navone, Graciela T; Diaz, Julia I

2018-03-01

Angiostrongyliasis is an infection caused by nematode worms of the genus Angiostrongylus. The adult worms inhabit the pulmonary arteries, heart, bronchioles of the lung, or mesenteric arteries of the caecum of definitive host. Of a total of 23 species of Angiostrongylus cited worldwide, only nine were registered in the American Continent. Two species, A. cantonensis and A. costaricensis, are considered zoonoses when the larvae accidentally parasitise man. In the present study, geographical and chronological distribution of definitive hosts of Angiostrongylus in the Americas is analysed in order to observe their relationship with disease reports. Moreover, the role of different definitive hosts as sentinels and dispersers of infective stages is discussed. The study area includes the Americas. First records of Angiostrongylus spp. in definitive or accidental hosts were compiled from the literature. Data were included in tables and figures and were matched to geographic information systems (GIS). Most geographical records of Angiostrongylus spp. both for definitive and accidental hosts belong to tropical areas, mainly equatorial zone. In relation to those species of human health importance, as A. cantonensis and A. costaricensis, most disease cases indicate a coincidence between the finding of definitive host and disease record. However, in some geographic site there are gaps between report of definitive host and disease record. In many areas, human populations have invaded natural environments and their socioeconomic conditions do not allow adequate medical care. Consequently, many cases for angiostrongyliasis could have gone unreported or unrecognised throughout history and in the nowadays. Moreover, the population expansion and the climatic changes invite to make broader and more complete range of observation on the species that involve possible epidemiological risks. This paper integrates and shows the current distribution of Angiostrongylus species in America

Angiostrongylus spp. in the Americas: geographical and chronological distribution of definitive hosts versus disease reports

Science.gov (United States)

Valente, Romina; Robles, Maria del Rosario; Navone, Graciela T; Diaz, Julia I

2018-01-01

BACKGROUND Angiostrongyliasis is an infection caused by nematode worms of the genus Angiostrongylus. The adult worms inhabit the pulmonary arteries, heart, bronchioles of the lung, or mesenteric arteries of the caecum of definitive host. Of a total of 23 species of Angiostrongylus cited worldwide, only nine were registered in the American Continent. Two species, A. cantonensis and A. costaricensis, are considered zoonoses when the larvae accidentally parasitise man. OBJECTIVES In the present study, geographical and chronological distribution of definitive hosts of Angiostrongylus in the Americas is analysed in order to observe their relationship with disease reports. Moreover, the role of different definitive hosts as sentinels and dispersers of infective stages is discussed. METHODS The study area includes the Americas. First records of Angiostrongylus spp. in definitive or accidental hosts were compiled from the literature. Data were included in tables and figures and were matched to geographic information systems (GIS). FINDINGS Most geographical records of Angiostrongylus spp. both for definitive and accidental hosts belong to tropical areas, mainly equatorial zone. In relation to those species of human health importance, as A. cantonensis and A. costaricensis, most disease cases indicate a coincidence between the finding of definitive host and disease record. However, in some geographic site there are gaps between report of definitive host and disease record. In many areas, human populations have invaded natural environments and their socioeconomic conditions do not allow adequate medical care. MAIN CONCLUSIONS Consequently, many cases for angiostrongyliasis could have gone unreported or unrecognised throughout history and in the nowadays. Moreover, the population expansion and the climatic changes invite to make broader and more complete range of observation on the species that involve possible epidemiological risks. This paper integrates and shows the

A model to estimate effects of SNPs on host susceptibility and infectivity for an endemic infectious disease.

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Biemans, Floor; de Jong, Mart C M; Bijma, Piter

2017-06-30

Infectious diseases in farm animals affect animal health, decrease animal welfare and can affect human health. Selection and breeding of host individuals with desirable traits regarding infectious diseases can help to fight disease transmission, which is affected by two types of (genetic) traits: host susceptibility and host infectivity. Quantitative genetic studies on infectious diseases generally connect an individual's disease status to its own genotype, and therefore capture genetic effects on susceptibility only. However, they usually ignore variation in exposure to infectious herd mates, which may limit the accuracy of estimates of genetic effects on susceptibility. Moreover, genetic effects on infectivity will exist as well. Thus, to design optimal breeding strategies, it is essential that genetic effects on infectivity are quantified. Given the potential importance of genetic effects on infectivity, we set out to develop a model to estimate the effect of single nucleotide polymorphisms (SNPs) on both host susceptibility and host infectivity. To evaluate the quality of the resulting SNP effect estimates, we simulated an endemic disease in 10 groups of 100 individuals, and recorded time-series data on individual disease status. We quantified bias and precision of the estimates for different sizes of SNP effects, and identified the optimum recording interval when the number of records is limited. We present a generalized linear mixed model to estimate the effect of SNPs on both host susceptibility and host infectivity. SNP effects were on average slightly underestimated, i.e. estimates were conservative. Estimates were less precise for infectivity than for susceptibility. Given our sample size, the power to estimate SNP effects for susceptibility was 100% for differences between genotypes of a factor 1.56 or more, and was higher than 60% for infectivity for differences between genotypes of a factor 4 or more. When disease status was recorded 11 times on each

GRAFT VERSUS HOST DISEASE- ORAL PRESENTATION

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Pradeep P. S

2017-09-01

Full Text Available BACKGROUND Graft-versus-host disease (GVHD is described as a potentially life-threatening complication caused by allogeneic haematopoietic cell transplantation. It is an exaggerated manifestation of a normal inflammatory mechanism in which donor lymphocytes encounter foreign antigens in an atmosphere that promote inflammation. 90% of the patients show oral features in case of cGVHD. Oral mucosal lesions and salivary gland dysfunction are the main oral features of chronic GVHD. Trismus or reduction of the mouth opening due to the perioral deposition of collagen is also commonly seen. Purpose of this review is to understand pathophysiology of oral presentations of GVHD. MATERIALS AND METHODS Review related to GVHD pathophysiology, oral lesions after haematopoietic cell transplant encompassed literature from 1966 through 2015. Review of Medline/PubMed Journals were done. RESULTS It is difficult to describe the pathophysiology of oral manifestations because there is no well accepted definition. CONCLUSION Larger well-designed clinical studies are needed to understand the pathobiology of oral cGVHD and determine best treatments for this disease.

Host phylogeny determines viral persistence and replication in novel hosts.

Directory of Open Access Journals (Sweden)

Ben Longdon

2011-09-01

Full Text Available Pathogens switching to new hosts can result in the emergence of new infectious diseases, and determining which species are likely to be sources of such host shifts is essential to understanding disease threats to both humans and wildlife. However, the factors that determine whether a pathogen can infect a novel host are poorly understood. We have examined the ability of three host-specific RNA-viruses (Drosophila sigma viruses from the family Rhabdoviridae to persist and replicate in 51 different species of Drosophilidae. Using a novel analytical approach we found that the host phylogeny could explain most of the variation in viral replication and persistence between different host species. This effect is partly driven by viruses reaching a higher titre in those novel hosts most closely related to the original host. However, there is also a strong effect of host phylogeny that is independent of the distance from the original host, with viral titres being similar in groups of related hosts. Most of this effect could be explained by variation in general susceptibility to all three sigma viruses, as there is a strong phylogenetic correlation in the titres of the three viruses. These results suggest that the source of new emerging diseases may often be predictable from the host phylogeny, but that the effect may be more complex than simply causing most host shifts to occur between closely related hosts.

Pathogenic landscapes: Interactions between land, people, disease vectors, and their animal hosts

Science.gov (United States)

2010-01-01

Background Landscape attributes influence spatial variations in disease risk or incidence. We present a review of the key findings from eight case studies that we conducted in Europe and West Africa on the impact of land changes on emerging or re-emerging vector-borne diseases and/or zoonoses. The case studies concern West Nile virus transmission in Senegal, tick-borne encephalitis incidence in Latvia, sandfly abundance in the French Pyrenees, Rift Valley Fever in the Ferlo (Senegal), West Nile Fever and the risk of malaria re-emergence in the Camargue, and rodent-borne Puumala hantavirus and Lyme borreliosis in Belgium. Results We identified general principles governing landscape epidemiology in these diverse disease systems and geographic regions. We formulated ten propositions that are related to landscape attributes, spatial patterns and habitat connectivity, pathways of pathogen transmission between vectors and hosts, scale issues, land use and ownership, and human behaviour associated with transmission cycles. Conclusions A static view of the "pathogenecity" of landscapes overlays maps of the spatial distribution of vectors and their habitats, animal hosts carrying specific pathogens and their habitat, and susceptible human hosts and their land use. A more dynamic view emphasizing the spatial and temporal interactions between these agents at multiple scales is more appropriate. We also highlight the complementarity of the modelling approaches used in our case studies. Integrated analyses at the landscape scale allows a better understanding of interactions between changes in ecosystems and climate, land use and human behaviour, and the ecology of vectors and animal hosts of infectious agents. PMID:20979609

Applying Precision Medicine and Immunotherapy Advances from Oncology to Host-Directed Therapies for Infectious Diseases.

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Mahon, Robert N; Hafner, Richard

2017-01-01

To meet the challenges of increasing antimicrobial resistance, the infectious disease community needs innovative therapeutics. Precision medicine and immunotherapies are transforming cancer therapeutics by targeting the regulatory signaling pathways that are involved not only in malignancies but also in the metabolic and immunologic function of the tumor microenvironment. Infectious diseases target many of the same regulatory pathways as they modulate host metabolic functions for their own nutritional requirements and to impede host immunity. These similarities and the advances made in precision medicine and immuno-oncology that are relevant for the current development of host-directed therapies (HDTs) to treat infectious diseases are discussed. To harness this potential, improvements in drug screening methods and development of assays that utilize the research tools including high throughput multiplexes already developed by oncology are essential. A multidisciplinary approach that brings together immunologists, infectious disease specialists, and oncologists will be necessary to fully develop the potential of HDTs.

Pretransplant Levels of CRP and Interleukin-6 Family Cytokines; Effects on Outcome after Allogeneic Stem Cell Transplantation

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Tor Henrik Tvedt

2016-11-01

Full Text Available Several pretransplant factors, including CRP (C-reactive protein levels, reflect the risk of complications after allogeneic stem cell transplantation. IL-6 induces CRP increase, and we therefore investigated the effects of pretransplant IL-6, soluble IL-6 receptors, IL-6 family cytokines and CRP serum levels on outcome for 100 consecutive allotransplant recipients. All patients had related donors, none had active infections and 99 patients were in complete remission before conditioning. The incidence of acute graft versus host disease (aGVHD requiring treatment was 40%, survival at Day +100 82%, and overall survival 48%. Despite a significant correlation between pretransplant CRP and IL-6 levels, only CRP levels significantly influenced transplant-related mortality (TRM. However, CRP did not influence overall survival (OS. Pretransplant IL-31 influenced late TRM. Finally, there was a significant association between pretransplant IL-6 and early postconditioning weight gain (i.e., fluid retention, and this fluid retention was a risk factor for aGVHD, TRM and OS. To conclude, pretransplant CRP, IL-31 and early posttransplant fluid retention were independent risk factors for TRM and survival after allotransplantation.

Modelling within-host spatiotemporal dynamics of invasive bacterial disease.

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Andrew J Grant

2008-04-01

Full Text Available Mechanistic determinants of bacterial growth, death, and spread within mammalian hosts cannot be fully resolved studying a single bacterial population. They are also currently poorly understood. Here, we report on the application of sophisticated experimental approaches to map spatiotemporal population dynamics of bacteria during an infection. We analyzed heterogeneous traits of simultaneous infections with tagged Salmonella enterica populations (wild-type isogenic tagged strains [WITS] in wild-type and gene-targeted mice. WITS are phenotypically identical but can be distinguished and enumerated by quantitative PCR, making it possible, using probabilistic models, to estimate bacterial death rate based on the disappearance of strains through time. This multidisciplinary approach allowed us to establish the timing, relative occurrence, and immune control of key infection parameters in a true host-pathogen combination. Our analyses support a model in which shortly after infection, concomitant death and rapid bacterial replication lead to the establishment of independent bacterial subpopulations in different organs, a process controlled by host antimicrobial mechanisms. Later, decreased microbial mortality leads to an exponential increase in the number of bacteria that spread locally, with subsequent mixing of bacteria between organs via bacteraemia and further stochastic selection. This approach provides us with an unprecedented outlook on the pathogenesis of S. enterica infections, illustrating the complex spatial and stochastic effects that drive an infectious disease. The application of the novel method that we present in appropriate and diverse host-pathogen combinations, together with modelling of the data that result, will facilitate a comprehensive view of the spatial and stochastic nature of within-host dynamics.

Long term follow up of patients after allogeneic stem cell transplantation and transfusion of HSV-Tk transduced T-cells.

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Eva Maria Weissinger

2015-04-01

Full Text Available Allogeneic stem cell transplantation (allo-HSCT is one of the curative treatments for hematologic malignancies, but is hampered by severe complications, such as acute or chronic graft-versus-host-disease (aGvHD; cGvHD and infections. CD34-selcetion of stem cells reduces the risk of aGvHD, but also leads to increased infectious complications and relapse. Thus, we studied the efficacy, safety and feasibility of transfer of gene modified donor T-cells shortly after allo-HSCT in two clinical trials between 2002 and 2007 and here we compare the results to unmodified donor leukocyte transfusion (DLI. The aim of these trials was to provide patients with the protection of T-cells after T-cell-depleted allo-HSCT in the matched or mismatched donor setting with an option to delete transduced T-cells, if severe aGvHD occurred within the trial period. Donor-T-cells were transduced with the replication-deficient retrovirus SFCMM-3, expressing HSV-Tk and the truncated LNGFR for selection of transduced cells. Transduced cells were transfused either after day +60 (matched donors or on day +42 (haploidentical donors.Nine patients were included in the first trial (MHH; 2002 until 2007 2 were included in TK007 (2005-2009 and 6 serve as a control group for outcome after haploidentical transplantation without HSV-TK-transduced DLI. Three patients developed acute GvHD, two had grade I of the skin, one had aGvHD on day +131 (post-HSCT; +89 post-HSV-Tk DLI grade II, which was successfully controlled by ganciclovir (GCV. Donor chimerism was stabilized after transfusion of the transduced cells in all patients treated. Functionality of HSV-Tk gene expressing T-cells was shown by loss of bcr-abl gene expression as well as by control of cytomegalovirus-reactivation. To date, 6patients have relapsed and died, 2 after a second HSCT without T-cell depletion or administration of unmodified T-cells. Eleven patients (7 post-HSV-Tk DLI are alive and well to date.

Optimal control issues in plant disease with host demographic factor and botanical fungicides

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Anggriani, N.; Mardiyah, M.; Istifadah, N.; Supriatna, A. K.

2018-03-01

In this paper, we discuss a mathematical model of plant disease with the effect of fungicide. We assume that the fungicide is given as a preventive treatment to infectious plants. The model is constructed based on the development of the disease in which the monomolecular is monocyclic. We show the value of the Basic Reproduction Number (BRN) ℛ0 of the plant disease transmission. The BRN is computed from the largest eigenvalue of the next generation matrix of the model. The result shows that in the region where ℛ0 greater than one there is a single stable endemic equilibrium. However, in the region where ℛ0 less than one this endemic equilibrium becomes unstable. The dynamics of the model is highly sensitive to changes in contact rate and infectious period. We also discuss the optimal control of the infected plant host by considering a preventive treatment aimed at reducing the infected host plant. The obtaining optimal control shows that it can reduce the number of infected hosts compared to that without control. Some numerical simulations are also given to illustrate our analytical results.

Disease ecology across soil boundaries: effects of below-ground fungi on above-ground host-parasite interactions.

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Tao, Leiling; Gowler, Camden D; Ahmad, Aamina; Hunter, Mark D; de Roode, Jacobus C

2015-10-22

Host-parasite interactions are subject to strong trait-mediated indirect effects from other species. However, it remains unexplored whether such indirect effects may occur across soil boundaries and connect spatially isolated organisms. Here, we demonstrate that, by changing plant (milkweed Asclepias sp.) traits, arbuscular mycorrhizal fungi (AMF) significantly affect interactions between a herbivore (the monarch butterfly Danaus plexippus) and its protozoan parasite (Ophryocystis elektroscirrha), which represents an interaction across four biological kingdoms. In our experiment, AMF affected parasite virulence, host resistance and host tolerance to the parasite. These effects were dependent on both the density of AMF and the identity of milkweed species: AMF indirectly increased disease in monarchs reared on some species, while alleviating disease in monarchs reared on other species. The species-specificity was driven largely by the effects of AMF on both plant primary (phosphorus) and secondary (cardenolides; toxins in milkweeds) traits. Our study demonstrates that trait-mediated indirect effects in disease ecology are extensive, such that below-ground interactions between AMF and plant roots can alter host-parasite interactions above ground. In general, soil biota may play an underappreciated role in the ecology of many terrestrial host-parasite systems. © 2015 The Author(s).

Inhibition of protein geranylgeranylation and farnesylation protects against graft-versus-host disease via effects on CD4 effector T cells.

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Hechinger, Anne-Kathrin; Maas, Kristina; Dürr, Christoph; Leonhardt, Franziska; Prinz, Gabriele; Marks, Reinhard; Gerlach, Ulrike; Hofmann, Maike; Fisch, Paul; Finke, Jürgen; Pircher, Hanspeter; Zeiser, Robert

2013-01-01

Despite advances in immunosuppressive regimens, acute graft-versus-host disease remains a frequent complication of allogeneic hematopoietic cell transplantation. Pathogenic donor T cells are dependent on correct attachment of small GTPases to the cell membrane, mediated by farnesyl- or geranylgeranyl residues, which, therefore, constitute potential targets for graft-versus-host disease prophylaxis. A mouse model was used to study the impact of a farnesyl-transferase inhibitor and a geranylgeranyl-transferase inhibitor on acute graft-versus-host disease, anti-cytomegalovirus T-cell responses and graft-versus-leukemia activity. Treatment of mice undergoing allogeneic hematopoietic cell transplantation with farnesyl-transferase inhibitor and geranylgeranyl-transferase inhibitor reduced the histological severity of graft-versus-host disease and prolonged survival significantly. Mechanistically, farnesyl-transferase inhibitor and geranylgeranyl-transferase inhibitor treatment resulted in reduced alloantigen-driven expansion of CD4 T cells. In vivo treatment led to increased thymic cellularity and polyclonality of the T-cell receptor repertoire by reducing thymic graft-versus-host disease. These effects were absent when squalene production was blocked. The farnesyl-transferase inhibitor and geranylgeranyl-transferase inhibitor did not compromise CD8 function against leukemia cells or reconstitution of T cells that were subsequently responsible for anti-murine cytomegalovirus responses. In summary, we observed an immunomodulatory effect of inhibitors of farnesyl-transferase and geranylgeranyl-transferase on graft-versus-host disease, with enhanced functional immune reconstitution. In the light of the modest toxicity of farnesyl-transferase inhibitors such as tipifarnib in patients and the potent reduction of graft-versus-host disease in mice, farnesyl-transferase and geranylgeranyl-transferase inhibitors could help to reduce graft-versus-host disease significantly without

Microbiome Profiles in Periodontitis in Relation to Host and Disease Characteristics

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Hong, Bo-Young; Furtado Araujo, Michel V.; Strausbaugh, Linda D.; Terzi, Evimaria; Ioannidou, Effie; Diaz, Patricia I.

2015-01-01

Periodontitis is an inflammatory condition that affects the supporting tissues surrounding teeth. The occurrence of periodontitis is associated with shifts in the structure of the communities that inhabit the gingival sulcus. Although great inter-subject variability in the subgingival microbiome has been observed in subjects with periodontitis, it is unclear whether distinct community types exist and if differences in microbial signatures correlate with host characteristics or with the variable clinical presentations of periodontitis. Therefore, in this study we explored the existence of different community types in periodontitis and their relationship with host demographic, medical and disease-related clinical characteristics. Clustering analyses of microbial abundance profiles suggested two types of communities (A and B) existed in the 34 subjects with periodontitis evaluated. Type B communities harbored greater proportions of certain periodontitis-associated taxa, including species historically associated with the disease, such as Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola, and taxa recently linked to periodontitis. In contrast, subjects with type A communities had increased proportions of different periodontitis-associated species, and were also enriched for health-associated species and core taxa (those equally prevalent in health and periodontitis). Periodontitis subgingival clusters were not associated with demographic, medical or disease-specific clinical parameters other than periodontitis extent (proportion of sites affected), which positively correlated with the total proportion of cluster B signature taxa. In conclusion, two types of microbial communities were detected in subjects with periodontitis. Host demographics and underlying medical conditions did not correlate with these profiles, which instead appeared to be related to periodontitis extent, with type B communities present in more widespread disease cases. The two

Host persistence or extinction from emerging infectious disease: insights from white-nose syndrome in endemic and invading regions.

Science.gov (United States)

Hoyt, Joseph R; Langwig, Kate E; Sun, Keping; Lu, Guanjun; Parise, Katy L; Jiang, Tinglei; Frick, Winifred F; Foster, Jeffrey T; Feng, Jiang; Kilpatrick, A Marm

2016-03-16

Predicting species' fates following the introduction of a novel pathogen is a significant and growing problem in conservation. Comparing disease dynamics between introduced and endemic regions can offer insight into which naive hosts will persist or go extinct, with disease acting as a filter on host communities. We examined four hypothesized mechanisms for host-pathogen persistence by comparing host infection patterns and environmental reservoirs for Pseudogymnoascus destructans (the causative agent of white-nose syndrome) in Asia, an endemic region, and North America, where the pathogen has recently invaded. Although colony sizes of bats and hibernacula temperatures were very similar, both infection prevalence and fungal loads were much lower on bats and in the environment in Asia than North America. These results indicate that transmission intensity and pathogen growth are lower in Asia, likely due to higher host resistance to pathogen growth in this endemic region, and not due to host tolerance, lower transmission due to smaller populations, or lower environmentally driven pathogen growth rate. Disease filtering also appears to be favouring initially resistant species in North America. More broadly, determining the mechanisms allowing species persistence in endemic regions can help identify species at greater risk of extinction in introduced regions, and determine the consequences for disease dynamics and host-pathogen coevolution. © 2016 The Author(s).

Molecular mechanisms of Porphyromonas gingivalis-host cell interaction on periodontal diseases

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Masaaki Nakayama

2017-11-01

Full Text Available Porphyromonas gingivalis (P. gingivalis is a major oral pathogen and associated with periodontal diseases including periodontitis and alveolar bone loss. In this review, we indicate that two virulence factors, which are hemoglobin receptor protein (HbR and cysteine proteases “gingipains”, expressed by P. gingivalis have novel functions on the pathogenicity of P. gingivalis. P. gingivalis produces three types of gingipains and concomitantly several adhesin domains. Among the adhesin domains, hemoglobin receptor protein (HbR, also called HGP15, has the function of induction of interleukin-8 (IL-8 expression in human gingival epithelial cells, indicating the possibility that HbR is associated with P. gingivalis-induced periodontal inflammation. On bacteria-host cells contact, P. gingivalis induces cellular signaling alteration in host cells. Phosphatidylinositol 3-kinase (PI3K and Akt are well known to play a pivotal role in various cellular physiological functions including cell survival and glucose metabolism in mammalian cells. Recently, we demonstrated that gingipains attenuate the activity of PI3K and Akt, which might have a causal influence on periodontal diseases by chronic infection to the host cells from the speculation of molecular analysis. In this review, we discuss new molecular and biological characterization of the virulence factors from P. gingivalis.

Corals hosting symbiotic hydrozoans are less susceptible to predation and disease

KAUST Repository

Montano, Simone

2017-12-20

In spite of growing evidence that climate change may dramatically affect networks of interacting species, whether-and to what extent-ecological interactions can mediate species\\' responses to disturbances is an open question. Here we show how a largely overseen association such as that between hydrozoans and scleractinian corals could be possibly associated with a reduction in coral susceptibility to ever-increasing predator and disease outbreaks. We examined 2455 scleractinian colonies (from both Maldivian and the Saudi Arabian coral reefs) searching for non-random patterns in the occurrence of hydrozoans on corals showing signs of different health conditions (i.e. bleaching, algal overgrowth, corallivory and different coral diseases). We show that, after accounting for geographical, ecological and co-evolutionary factors, signs of disease and corallivory are significantly lower in coral colonies hosting hydrozoans than in hydrozoan-free ones. This finding has important implications for our understanding of the ecology of coral reefs, and for their conservation in the current scenario of global change, because it suggests that symbiotic hydrozoans may play an active role in protecting their scleractinian hosts from stresses induced by warming water temperatures.

Emerging prion disease drives host selection in a wildlife population

Science.gov (United States)

Robinson, Stacie J.; Samuel, Michael D.; Johnson, Chad J.; Adams, Marie; McKenzie, Debbie I.

2012-01-01

Infectious diseases are increasingly recognized as an important force driving population dynamics, conservation biology, and natural selection in wildlife populations. Infectious agents have been implicated in the decline of small or endangered populations and may act to constrain population size, distribution, growth rates, or migration patterns. Further, diseases may provide selective pressures that shape the genetic diversity of populations or species. Thus, understanding disease dynamics and selective pressures from pathogens is crucial to understanding population processes, managing wildlife diseases, and conserving biological diversity. There is ample evidence that variation in the prion protein gene (PRNP) impacts host susceptibility to prion diseases. Still, little is known about how genetic differences might influence natural selection within wildlife populations. Here we link genetic variation with differential susceptibility of white-tailed deer to chronic wasting disease (CWD), with implications for fitness and disease-driven genetic selection. We developed a single nucleotide polymorphism (SNP) assay to efficiently genotype deer at the locus of interest (in the 96th codon of the PRNP gene). Then, using a Bayesian modeling approach, we found that the more susceptible genotype had over four times greater risk of CWD infection; and, once infected, deer with the resistant genotype survived 49% longer (8.25 more months). We used these epidemiological parameters in a multi-stage population matrix model to evaluate relative fitness based on genotype-specific population growth rates. The differences in disease infection and mortality rates allowed genetically resistant deer to achieve higher population growth and obtain a long-term fitness advantage, which translated into a selection coefficient of over 1% favoring the CWD-resistant genotype. This selective pressure suggests that the resistant allele could become dominant in the population within an

Implications of host genetic variation on the risk and prevalence of infectious diseases transmitted through the environment.

Science.gov (United States)

Doeschl-Wilson, Andrea B; Davidson, R; Conington, J; Roughsedge, T; Hutchings, M R; Villanueva, B

2011-07-01

Previous studies have shown that host genetic heterogeneity in the response to infectious challenge can affect the emergence risk and the severity of diseases transmitted through direct contact between individuals. However, there is substantial uncertainty about the degree and direction of influence owing to different definitions of genetic variation, most of which are not in line with the current understanding of the genetic architecture of disease traits. Also, the relevance of previous results for diseases transmitted through environmental sources is unclear. In this article a compartmental genetic-epidemiological model was developed to quantify the impact of host genetic diversity on epidemiological characteristics of diseases transmitted through a contaminated environment. The model was parameterized for footrot in sheep. Genetic variation was defined through continuous distributions with varying shape and degree of dispersion for different disease traits. The model predicts a strong impact of genetic heterogeneity on the disease risk and its progression and severity, as well as on observable host phenotypes, when dispersion in key epidemiological parameters is high. The impact of host variation depends on the disease trait for which variation occurs and on environmental conditions affecting pathogen survival. In particular, compared to homogeneous populations with the same average susceptibility, disease risk and severity are substantially higher in populations containing a large proportion of highly susceptible individuals, and the differences are strongest when environmental contamination is low. The implications of our results for the recording and analysis of disease data and for predicting response to selection are discussed.

Contentious host-microbiota relationship in inflammatory bowel disease--can foes become friends again?

Science.gov (United States)

Satokari, Reetta

2015-01-01

Inflammatory bowel diseases (IBDs) are chronic debilitating disorders of unknown etiology, consisting of two main conditions, ulcerative colitis and Crohn's disease. Major advances have recently taken place in human genetic studies of IBD and over 160 risk loci for these two diseases have been uncovered. These genetic data highlight a key role for genes that code for immunological and epithelial barrier functions. Environmental factors also make substantial contributions to the pathogenesis of IBD and account for the growing incidence of the diseases around the world. Intestinal microbiota creates resistance to infection, provides nutrients, and educates the immune system and in many ways has a significant impact on human health. Aberrant microbiota composition and decreased diversity (dysbiotic microbiota) are key etiopathological events in IBD. Dysbiotic microbiota can lead to loss of normal, regulatory immune effects in the gut mucosa. This may play a central role in the development and perpetuation of chronic inflammation. Further, the expression of specific innate immune receptors that recognize microbes is altered in the IBD epithelium. Therefore, the combination of host side epithelial barrier functions and the presence of dysbiotic microbiota in the gut together promote inflammation. New therapeutic options targeting microbiota are currently considered for IBD and they may, in the future, provide means to reverse the pathogenic host-microbiota relationship into a symbiotic one. In this review, the focus is on the intestinal microbiota and host-microbe interactions in IBD.

Host-seeking behavior and dispersal of Triatoma infestans, a vector of Chagas disease, under semi-field conditions.

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Ricardo Castillo-Neyra

2015-01-01

Full Text Available Chagas disease affects millions of people in Latin America. The control of this vector-borne disease focuses on halting transmission by reducing or eliminating insect vector populations. Most transmission of Trypanosoma cruzi, the causative agent of Chagas disease, involves insects living within or very close to households and feeding mostly on domestic animals. As animal hosts can be intermittently present it is important to understand how host availability can modify transmission risk to humans and to characterize the host-seeking dispersal of triatomine vectors on a very fine scale. We used a semi-field system with motion-detection cameras to characterize the dispersal of Triatoma infestans, and compare the behavior of vector populations in the constant presence of hosts (guinea pigs, and after the removal of the hosts. The emigration rate - net insect population decline in original refuge - following host removal was on average 19.7% of insects per 10 days compared to 10.2% in constant host populations (p = 0.029. However, dispersal of T. infestans occurred in both directions, towards and away from the initial location of the hosts. The majority of insects that moved towards the original location of guinea pigs remained there for 4 weeks. Oviposition and mortality were observed and analyzed in the context of insect dispersal, but only mortality was higher in the group where animal hosts were removed (p-value <0.01. We discuss different survival strategies associated with the observed behavior and its implications for vector control. Removing domestic animals in infested areas increases vector dispersal from the first day of host removal. The implications of these patterns of vector dispersal in a field setting are not yet known but could result in movement towards human rooms.

Fototerapia na doença enxerto contra hospedeiro Phototherapy in the graft versus host disease

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Ida Duarte

2008-10-01

Full Text Available FUNDAMENTOS: A doença enxerto contra hospedeiro é um dos obstáculos ao sucesso do transplante de medula óssea, e o envolvimento cutâneo é freqüente. A fototerapia é utilizada devido à intensa atividade imunomoduladora local, sendo opção terapêutica adjuvante para as lesões cutâneas resistentes à terapia convencional. OBJETIVO: Realizar análise descritiva do tratamento da doença enxerto contra hospedeiro com fototerapia (Puva ou UVB de faixa estreita. MÉTODOS: Foram atendidos nove pacientes com manifestação cutânea da doença enxerto contra hospedeiro aguda ou crônica. Seis foram tratados com Puva, terapia de primeira escolha, e três com UVB de faixa estreita. As sessões foram realizadas três vezes por semana, e a resposta terapêutica avaliada após 12 sessões. RESULTADOS: Todos os pacientes com doença enxerto contra hospedeiro aguda mostraram melhora, com desaparecimento do eritema e do edema. Naqueles com doença crônica, observaram-se involução das lesões liquenóides e melhora da mobilidade daqueles com a forma esclerodermiforme. Dois pacientes apresentaram doença de evolução grave e foram a óbito. CONCLUSÃO: A fototerapia mostrou-se efetiva no tratamento das manifestações cutâneas da doença enxerto contra hospedeiro aguda e crônica. A Puva permite o controle da doença, podendo a UVB de faixa estreita ser opção para pacientes impossibilitados de usar medicação sistêmica.BACKGROUND: Graft versus host disease is one of the obstacles to successful bone marrow transplantation. It often affects the skin. Phototherapy has been used because of its strong local immunomodulatory activity and it is an option for adjuvant therapy for skin lesions of graft versus host disease resistant to conventional therapy. OBJECTIVE: To make a descriptive analysis of treating graft versus host disease with phototherapy (PUVA or narrowband UVB. Methods - Nine patients with cutaneous manifestation of acute or chronic

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.

Host-bacterial interplay in periodontal disease

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Rudrakshi Chickanna

2015-01-01

Full Text Available A literature search was performed using MEDLINE (PubMed and other electronic basis from 1991 to 2014. Search included books and journals based on the systematic and critical reviews, in vitro and in vivo clinical studies on molecular basis of host microbial interactions. Clearly, an understanding of the host susceptibility factor in addition to microbial factors by elucidating the molecular basis offers opportunity for therapeutic manipulation of advancing periodontal destruction. One of the hallmarks of pathogenesis is the ability of pathogenic organisms to invade surrounding tissues and to evade the host defence. This paper focuses the general overview of molecular mechanisms involved in the microbiota and host response to bacterial inimical behavior in periodontics.

Cotransplantation of haploidentical hematopoietic and umbilical cord mesenchymal stem cells for severe aplastic anemia: Successful engraftment and mild GVHD

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Wu Yamei

2014-01-01

Full Text Available Haploidentical hematopoietic stem-cell transplantation (haplo-HSCT is associated with an increased risk of graft failure and severe graft-versus-host disease (GVHD. Mesenchymal stromal cells (MSCs have been shown to support in vivo normal hematopoiesis and to display potent immunesuppressive effects. We cotransplanted the culture-expanded third-party donor-derived umbilical cord MSCs (UC-MSCs in 21 young people with severe aplastic anemia (SAA undergoing haplo-HSCT without T-cell-depleted. We observed that all patients had sustained hematopoietic engraftment without any adverse UC-MSC infusion-related events. Furthermore, we did not observe any increase in severe aGVHD. These data suggest that UC-MSCs, possibly thanks to their potent immunosuppressive effect on allo-reactive host T lymphocytes escaping the preparative regimen, reduce the risk of graft failure and severe GVHD in haplo-HSCT.

Hydrogen, a potential safeguard for graft-versus-host disease and graft ischemia-reperfusion injury?

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Yuan, Lijuan; Shen, Jianliang

2016-01-01

Post-transplant complications such as graft-versus-host disease and graft ischemia-reperfusion injury are crucial challenges in transplantation. Hydrogen can act as a potential antioxidant, playing a preventive role against post-transplant complications in animal models of multiple organ transplantation. Herein, the authors review the current literature regarding the effects of hydrogen on graft ischemia-reperfusion injury and graft-versus-host disease. Existing data on the effects of hydrogen on ischemia-reperfusion injury related to organ transplantation are specifically reviewed and coupled with further suggestions for future work. The reviewed studies showed that hydrogen (inhaled or dissolved in saline) improved the outcomes of organ transplantation by decreasing oxidative stress and inflammation at both the transplanted organ and the systemic levels. In conclusion, a substantial body of experimental evidence suggests that hydrogen can significantly alleviate transplantation-related ischemia-reperfusion injury and have a therapeutic effect on graft-versus-host disease, mainly via inhibition of inflammatory cytokine secretion and reduction of oxidative stress through several underlying mechanisms. Further animal experiments and preliminary human clinical trials will lay the foundation for hydrogen use as a drug in the clinic. PMID:27652837

Subacute radiation dermatitis: a histologic imitator of acute cutaneous graft-versus-host disease

International Nuclear Information System (INIS)

LeBoit, P.E.

1989-01-01

The histopathologic changes of radiation dermatitis have been classified either as early effects (necrotic keratinocytes, fibrin thrombi, and hemorrhage) or as late effects (vacuolar changes at the dermal-epidermal junction, atypical radiation fibroblasts, and fibrosis). Two patients, one exposed to radiation therapeutically and one accidentally, are described. Skin biopsy specimens showed an interface dermatitis characterized by numerous dyskeratotic epidermal cells with lymphocytes in close apposition (satellite cell necrosis); that is, the epidermal changes were similar to those in acute graft-versus-host disease. Because recipients of bone marrow transplants frequently receive total body irradiation as part of their preparatory regimen, the ability of radiation to cause persistent epidermal changes similar to those in acute graft-versus-host disease could complicate the interpretation of posttransplant skin biopsy specimens

Chronic graft versus host disease and nephrotic syndrome

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Samia Barbouch

2014-01-01

Full Text Available Disturbed kidney function is a common complication after bone marrow transplantation. Recently, attention has been given to immune-mediated glomerular damage related to graft versus host disease (GVHD. We describe a 19-year-old woman who developed membranous glomerulonephritis after bone marrow transplantation (BMT. Six months later, she developed soft palate, skin and liver lesions considered to be chronic GVHD. Fifteen months after undergoing BMT, this patient presented with nephrotic syndrome. A renal biopsy showed mem-branous glomerulonephritis associated with a focal segmental glomerulosclerosis. She was started on corticosteroid treatment with good outcome.

Salivary mucins in host defense and disease prevention

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Erica Shapiro Frenkel

2015-12-01

Full Text Available Mucus forms a protective coating on wet epithelial surfaces throughout the body that houses the microbiota and plays a key role in host defense. Mucins, the primary structural components of mucus that creates its viscoelastic properties, are critical components of the gel layer that protect against invading pathogens. Altered mucin production has been implicated in diseases such as ulcerative colitis, asthma, and cystic fibrosis, which highlights the importance of mucins in maintaining homeostasis. Different types of mucins exist throughout the body in various locations such as the gastrointestinal tract, lungs, and female genital tract, but this review will focus on mucins in the oral cavity. Salivary mucin structure, localization within the oral cavity, and defense mechanisms will be discussed. These concepts will then be applied to present what is known about the protective function of mucins in oral diseases such as HIV/AIDS, oral candidiasis, and dental caries.

Brazilian status in blood irradiation in Graft-Versus-Host Disease (GVHD) prevention

International Nuclear Information System (INIS)

Goes, E.G. de; Borges, J.C.; Ghilardi Netto, T.

1996-01-01

A short overview of the Brazilian reality concerning Graft-Versus-Host Disease (GVHD) is presented. Suggestions of policies and procedures to optimise GVHD prevention are reported. A national irradiator device using cobalt teletherapy unit is proposed for irradiation of blood and cellular components

Pathogenic mechanisms of Acute Graft versus Host Disease

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Ferrara James L.M.

2002-01-01

Full Text Available Graft-versus-host-disease (GVHD is the major complication of allogeneic Bone Marrow Transplant (BMT. Older BMT recipients are a greater risk for acute GVHD after allogeneic BMT, but the causes of this association are poorly understood. Using well-characterized murine BMT models we have explored the mechanisms of increased GVHD in older mice. GVHD mortality and morbidity, and pathologic and biochemical indices were all worse in old recipients. Donor T cell responses were significantly increased in old recipients both in vivo and in vitro when stimulated by antigen-presenting cells (APCs from old mice. In a haploidential GVHD model, CD4+ donor T cells mediated more severe GVHD in old mice. We confirmed the role of aged APCs in GVHD using bone marrow chimera recipient created with either old or young bone marrow. APCs from these mice also stimulated greater responses from allogeneic cells in vitro. In a separate set of experiments we evaluated whether alloantigen expression on host target epithelium is essential for tissue damage induced by GVHD. Using bone marrow chimeras recipients in which either MHC II or MHC I alloantigen was expressed only on APCs, we found that acute GVHD does not require alloantigen expression on host target epithelium and that neutralization of tumor necrosis factor-alpha and interleukin-1 prevents acute GVHD. These results pertain to CD4-mediated GVHD and to a lesser extent in CD8-mediated GVHD, and confirm the central role of most APCs as well as inflammatory cytokines.

Host age modulates within-host parasite competition.

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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.

Understanding the Effects of Host Evolution and Skin Bacteria Composition on Disease Vector Choices

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2016-04-14

Distribution Unlimited UU UU UU UU 14-04-2016 1-Sep-2014 31-Dec-2015 Final Report: Understanding the effects of host evolution and skin bacteria ...S) AND ADDRESS (ES) U.S. Army Research Office P.O. Box 12211 Research Triangle Park, NC 27709-2211 mosquito, skin, bacteria , primate REPORT...reviewed journals: Final Report: Understanding the effects of host evolution and skin bacteria composition on disease vector choices Report Title Here

Infection history of the blood-meal host dictates pathogenic potential of the Lyme disease spirochete within the feeding tick vector.

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Bharti Bhatia

2018-04-01

Full Text Available Lyme disease in humans is caused by several genospecies of the Borrelia burgdorferi sensu lato (s.l. complex of spirochetal bacteria, including B. burgdorferi, B. afzelii and B. garinii. These bacteria exist in nature as obligate parasites in an enzootic cycle between small vertebrate hosts and Ixodid tick vectors, with humans representing incidental hosts. During the natural enzootic cycle, infected ticks in endemic areas feed not only upon naïve hosts, but also upon seropositive infected hosts. In the current study, we considered this environmental parameter and assessed the impact of the immune status of the blood-meal host on the phenotype of the Lyme disease spirochete within the tick vector. We found that blood from a seropositive host profoundly attenuates the infectivity (>104 fold of homologous spirochetes within the tick vector without killing them. This dramatic neutralization of vector-borne spirochetes was not observed, however, when ticks and blood-meal hosts carried heterologous B. burgdorferi s.l. strains, or when mice lacking humoral immunity replaced wild-type mice as blood-meal hosts in similar experiments. Mechanistically, serum-mediated neutralization does not block induction of host-adapted OspC+ spirochetes during tick feeding, nor require tick midgut components. Significantly, this study demonstrates that strain-specific antibodies elicited by B. burgdorferi s.l. infection neutralize homologous bacteria within feeding ticks, before the Lyme disease spirochetes enter a host. The blood meal ingested from an infected host thereby prevents super-infection by homologous spirochetes, while facilitating transmission of heterologous B. burgdorferi s.l. strains. This finding suggests that Lyme disease spirochete diversity is stably maintained within endemic populations in local geographic regions through frequency-dependent selection of rare alleles of dominant polymorphic surface antigens.

[Pretreatment doses of antithymocyte globubin-fresenius for allogeneic hematopoietic stem cell transplantation for beta-thalassemia major].

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Li, Chunfu; Wang, Yanhua; Wu, Xuedong; Pei, Fuyu; He, Yuelin; Feng, Xiaoqin; Liu, Huaying

2012-05-01

To investigate the effects of different doses of antithymocyte globubin-fresenius (ATG-F) for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with beta-thalassemia Major. Sixty-four children with beta-thalassemia major undergoing allo-HSCT were divided into two equal groups to receive ATG-F pretreatments at high (30 mg/kg) or low (15 mg/kg) doses as part of the conditioning regimen including mainly cyclophosphamide, busulfan, fludarabine, and thiotepa. The outcomes of the patients were compared between the two groups. No obvious difference were noted in the time to leukocyte and platelet engraftment between the two groups. The incidence of grade II-IV acute graft-versus-host disease (aGVHD) appeared to be higher in the low-dose group than in the high-dose group (12.5% vs 9.4%). The incidence of grade III-IV aGVHD was also higher in the low dose group (12.5% vs 6.3%), but the difference was not statistically significant. Application of high-dose ATG-F was associated with a higher rate of probable and possible fungal infection (P<0.05). The two doses of ATG-F is feasible as a part of the conditioning regimen for allo-HSCT in children with beta-thalassemia major.

Polymorphism in the interleukin-7 receptor-alpha and outcome after allogeneic hematopoietic cell transplantation with matched unrelated donor.

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Shamim, Z; Spellman, S; Haagenson, M; Wang, T; Lee, S J; Ryder, L P; Müller, K

2013-08-01

Interleukin-7 (IL-7) is essential for T cell development in the thymus and maintenance of peripheral T cells. The α-chain of the IL-7R is polymorphic with the existence of SNPs that give rise to non-synonymous amino acid substitutions. We previously found an association between donor genotypes and increased treatment-related mortality (TRM) (rs1494555G) and acute graft versus host disease (aGvHD) (rs1494555G and rs1494558T) after hematopoietic cell transplantation (HCT). Some studies have confirmed an association between rs6897932C and multiple sclerosis. In this study, we evaluated the prognostic significance of IL-7Rα SNP genotypes in 590-recipient/donor pairs that received HLA-matched unrelated donor HCT for haematological malignancies. Consistent with the primary studies, the rs1494555GG and rs1494558TT genotypes of the donor were associated with aGvHD and chronic GvHD in the univariate analysis. The Tallele of rs6897932 was suggestive of an association with increased frequency of relapse by univariate analysis (P = 0.017) and multivariate analysis (P = 0.015). In conclusion, this study provides further evidence of a role of the IL-7 pathway and IL-7Rα SNPs in HCT. © 2013 John Wiley & Sons Ltd.

Detection and Host Range Study of Virus Associated with Pepper Yellow Leaf Curl Disease

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SRI SULANDARI

2006-03-01

Full Text Available High incidence of Pepper yellow leaf curl virus (PepYLCV was observed in Indonesia since early 2000. Disease incidence in Yogyakarta, Central and West Java reached 100% on Capsicum frutescens, but only 10-35% on C. annuum. As an exception, the disease incidence on C. annuum cv. TM 999 was in the range of 70-100%. The causal agent of the disease, PepYLCV, was detected by polymerase chain reaction. Viral specific DNA fragment of the size ~1600 bp and ~550 bp was amplified from infected plants using two pairs of geminivirus universal primers pAL1v1978/pAL1c715, and pAv494/pAc1048, respectively. The PepYLCV has an intermediate host range including plants belonging to the family of Solanaceae, Leguminosae, and Compositae. The species belonging to the families of Cucurbitaceae, Malvaceae, Chenopodiaceae, and Amaranthaceae were resistant to the virus. Physalis floridana, is very prospective as a propagation host for the geminivirus infecting pepper. Nicotiana spp., cucumber, watermelon, cotton, and Sida sp. could be used as a differential host. Besides, Capsicum frutescens cv. Cakra, tomato, N. benthamiana, N. glutinosa, and Ageratum conyzoides could be used as indicator plants for the geminivirus infecting pepper.

Molecules at the interface of Cryptococcus and the host that determine disease susceptibility.

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Wozniak, Karen L; Olszewski, Michal A; Wormley, Floyd L

2015-05-01

Cryptococcus neoformans and Cryptococcus gattii, the predominant etiological agents of cryptococcosis, are fungal pathogens that cause disease ranging from a mild pneumonia to life-threatening infections of the central nervous system (CNS). Resolution or exacerbation of Cryptococcus infection is determined following complex interactions of several host and pathogen derived factors. Alternatively, interactions between the host and pathogen may end in an impasse resulting in the establishment of a sub-clinical Cryptococcus infection. The current review addresses the delicate interaction between the host and Cryptococcus-derived molecules that determine resistance or susceptibility to infection. An emphasis will be placed on data highlighted at the recent 9th International Conference on Cryptococcus and Cryptococcosis (ICCC). Copyright © 2015. Published by Elsevier Inc.

Mesenchymal stromal cells in the antimicrobial host response of hematopoietic stem cell recipients with graft-versus-host disease--friends or foes?

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Balan, A; Lucchini, G; Schmidt, S; Schneider, A; Tramsen, L; Kuçi, S; Meisel, R; Bader, P; Lehrnbecher, T

2014-10-01

Mesenchymal stromal cells (MSCs) are multipotent cells, which exhibit broad immunosuppressive activities. Moreover, they may be administered irrespectively of human leukocyte antigen (HLA) compatibility, without inducing life-threatening immunological reactions, as they express no HLA class II and limited HLA class I antigens under resting conditions. These characteristics have made MSC an appealing candidate for cell therapy after hematopoietic stem cell transplantation (HSCT), for example, for treatment of graft-versus-host disease (GvHD) or for graft rejection prevention/treatment in allogeneic HSCT recipients. Unfortunately, information regarding the effect of MSC infusion on the host response to infectious agents is scarce, and study results on infectious complications in patients receiving MSC are conflicting. The present review focuses on the available data from in vitro studies and animal models regarding the interaction of MSC with bacterial, viral and fungal pathogens. In a clinical part, we present the current information on infectious complications in allogeneic HSCT recipients who had received MSCs as prophylaxis or treatment of GvHD disease.

Pneumatosis cystoides interstitialis: A complication of graft-versus-host disease. A report of two cases.

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Laskowska, Katarzyna; Burzyńska-Makuch, Małgorzata; Krenska, Anna; Kołtan, Sylwia; Chrupek, Małgorzata; Nawrocka, Elżbieta; Lasek, Władysław; Serafin, Zbigniew

2012-04-01

Pneumatosis cystoides intestinalis (PCI) is a rare disorder characterized by the presence of multiple gas collections in the subserosal or submucosal intestinal wall of the large or small intestine. We report two cases of PCI in the course of chronic graft-versus-host disease. A 5-year-old girl was treated for acute lymphoblastic leukemia. Twenty-four months after the hematopoietic stem cell transplantation, in the course of graft-versus-host disease, she developed subcutaneous emphysema of the right inguinal and pudendal region. PCI was diagnosed based on a CT examination. A 3-year-old boy was treated for juvenile myelomonocytic leukemia. Fourteen months after the hematopoietic stem cell transplantation he presented with an increased severity of intestinal symptoms, including intermittent bleeding from large intestine. PCI was diagnosed based on a CT exam and was confirmed by a colonoscopy. Pneumatosis cystoides interstitialis in the course of chronic graft-versus-host disease has a heterogeneous clinical presentation that does not correlate with results of imaging. CT is a method of choice to diagnose PCI. In patients with PCI, the presence of free air in the peritoneal cavity does not confirm an intestinal perforation.

Pneumatosis cystoides interstitialis: A complication of graft-versus-host disease. A report of two cases

International Nuclear Information System (INIS)

Laskowska, Katarzyna; Burzyńska-Makuch, Małgorzata; Krenska, Anna; Kołtan, Sylwia; Chrupek, Małgorzata; Nawrocka, Elżbieta; Lasek, Władysław; Serafin, Zbigniew

2012-01-01

Pneumatosis cystoides intestinalis (PCI) is a rare disorder characterized by the presence of multiple gas collections in the subserosal or submucosal intestinal wall of the large or small intestine. We report two cases of PCI in the course of chronic graft-versus-host disease. A 5-year-old girl was treated for acute lymphoblastic leukemia. Twenty-four months after the hematopoietic stem cell transplantation, in the course of graft-versus-host disease, she developed subcutaneous emphysema of the right inguinal and pudendal region. PCI was diagnosed based on a CT examination. A 3-year-old boy was treated for juvenile myelomonocytic leukemia. Fourteen months after the hematopoietic stem cell transplantation he presented with an increased severity of intestinal symptoms, including intermittent bleeding from large intestine. PCI was diagnosed based on a CT exam and was confirmed by a colonoscopy. Pneumatosis cystoides interstitialis in the course of chronic graft-versus-host disease has a heterogeneous clinical presentation that does not correlate with results of imaging. CT is a method of choice to diagnose PCI. In patients with PCI, the presence of free air in the peritoneal cavity does not confirm an intestinal perforation

Radiographic features of esophageal involvement in chronic graft-vs.-host disease

International Nuclear Information System (INIS)

McDonald, G.B.; Sullivan, K.M.; Plumley, T.F.

1984-01-01

Chronic graft-vs.-host disease (GVHD) is an important late complication of allogeneic bone-marrow transplantation. It resembles several naturally occurring autoimmune diseases and involves the skin, mouth, eyes, liver, and esophagus. The radiographic findings of 14 symptomatic patients with chronic GVHD involving the esophagus were reviewed and found to include webs, ringlike narrowings, and tapering strictures in the mid and upper esophagus. Esophagoscopy revealed characteristic desquamation in the 13 patients studied, but barium studies detected this lesion in only one patient. Knowledge of the site and characteristics of esophageal involvement with chronic GVHD assists the radiologic evaluation of this disorder

A Systems Biology Approach to Infectious Disease Research: Innovating the Pathogen-Host Research Paradigm

Energy Technology Data Exchange (ETDEWEB)

Aderem, Alan; Adkins, Joshua N.; Ansong, Charles; Galagan, James; Kaiser, Shari; Korth, Marcus J.; Law, G. L.; McDermott, Jason E.; Proll, Sean; Rosenberger, Carrie; Schoolnik, Gary; Katze, Michael G.

2011-02-01

The 20th century was marked by extraordinary advances in our understanding of microbes and infectious disease, but pandemics remain, food and water borne illnesses are frequent, multi-drug resistant microbes are on the rise, and the needed drugs and vaccines have not been developed. The scientific approaches of the past—including the intense focus on individual genes and proteins typical of molecular biology—have not been sufficient to address these challenges. The first decade of the 21st century has seen remarkable innovations in technology and computational methods. These new tools provide nearly comprehensive views of complex biological systems and can provide a correspondingly deeper understanding of pathogen-host interactions. To take full advantage of these innovations, the National Institute of Allergy and Infectious Diseases recently initiated the Systems Biology Program for Infectious Disease Research. As participants of the Systems Biology Program we think that the time is at hand to redefine the pathogen-host research paradigm.

Immunopathogenesis and Virus–Host Interactions of Enterovirus 71 in Patients with Hand, Foot and Mouth Disease

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Cox, Jonathan A.; Hiscox, Julian A.; Solomon, Tom; Ooi, Mong-How; Ng, Lisa F. P.

2017-01-01

Enterovirus 71 (EV71) is a global infectious disease that affects millions of people. The virus is the main etiological agent for hand, foot, and mouth disease with outbreaks and epidemics being reported globally. Infection can cause severe neurological, cardiac, and respiratory problems in children under the age of 5. Despite on-going efforts, little is known about the pathogenesis of EV71, how the host immune system responds to the virus and the molecular mechanisms behind these responses. Moreover, current animal models remain limited, because they do not recapitulate similar disease patterns and symptoms observed in humans. In this review the role of the host–viral interactions of EV71 are discussed together with the various models available to examine: how EV71 utilizes its proteins to cleave host factors and proteins, aiding virus replication; how EV71 uses its own viral proteins to disrupt host immune responses and aid in its immune evasion. These discoveries along with others, such as the EV71 crystal structure, have provided possible targets for treatment and drug interventions. PMID:29238324

The Influence of Host and Bacterial Genotype on the Development of Disseminated Disease with Mycobacterium tuberculosis

Science.gov (United States)

Caws, Maxine; Thwaites, Guy; Dunstan, Sarah; Hawn, Thomas R.; Thi Ngoc Lan, Nguyen; Thuong, Nguyen Thuy Thuong; Stepniewska, Kasia; Huyen, Mai Nguyet Thu; Bang, Nguyen Duc; Huu Loc, Tran; Gagneux, Sebastien; van Soolingen, Dick; Kremer, Kristin; van der Sande, Marianne; Small, Peter; Thi Hoang Anh, Phan; Chinh, Nguyen Tran; Thi Quy, Hoang; Thi Hong Duyen, Nguyen; Quang Tho, Dau; Hieu, Nguyen T.; Torok, Estee; Hien, Tran Tinh; Dung, Nguyen Huy; Thi Quynh Nhu, Nguyen; Duy, Phan Minh; van Vinh Chau, Nguyen; Farrar, Jeremy

2008-01-01

The factors that govern the development of tuberculosis disease are incompletely understood. We hypothesized that some strains of Mycobacterium tuberculosis (M. tuberculosis) are more capable of causing disseminated disease than others and may be associated with polymorphisms in host genes responsible for the innate immune response to infection. We compared the host and bacterial genotype in 187 Vietnamese adults with tuberculous meningitis (TBM) and 237 Vietnamese adults with uncomplicated pulmonary tuberculosis. The host genotype of tuberculosis cases was also compared with the genotype of 392 cord blood controls from the same population. Isolates of M. tuberculosis were genotyped by large sequence polymorphisms. The hosts were defined by polymorphisms in genes encoding Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) and Toll-like receptor-2 (TLR-2). We found a significant protective association between the Euro-American lineage of M. tuberculosis and pulmonary rather than meningeal tuberculosis (Odds ratio (OR) for causing TBM 0.395, 95% confidence intervals (C.I.) 0.193–0.806, P = 0.009), suggesting these strains are less capable of extra-pulmonary dissemination than others in the study population. We also found that individuals with the C allele of TLR-2 T597C allele were more likely to have tuberculosis caused by the East-Asian/Beijing genotype (OR = 1.57 [95% C.I. 1.15–2.15]) than other individuals. The study provides evidence that M. tuberculosis genotype influences clinical disease phenotype and demonstrates, for the first time, a significant interaction between host and bacterial genotypes and the development of tuberculosis. PMID:18369480

The influence of host and bacterial genotype on the development of disseminated disease with Mycobacterium tuberculosis.

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Maxine Caws

2008-03-01

Full Text Available The factors that govern the development of tuberculosis disease are incompletely understood. We hypothesized that some strains of Mycobacterium tuberculosis (M. tuberculosis are more capable of causing disseminated disease than others and may be associated with polymorphisms in host genes responsible for the innate immune response to infection. We compared the host and bacterial genotype in 187 Vietnamese adults with tuberculous meningitis (TBM and 237 Vietnamese adults with uncomplicated pulmonary tuberculosis. The host genotype of tuberculosis cases was also compared with the genotype of 392 cord blood controls from the same population. Isolates of M. tuberculosis were genotyped by large sequence polymorphisms. The hosts were defined by polymorphisms in genes encoding Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP and Toll-like receptor-2 (TLR-2. We found a significant protective association between the Euro-American lineage of M. tuberculosis and pulmonary rather than meningeal tuberculosis (Odds ratio (OR for causing TBM 0.395, 95% confidence intervals (C.I. 0.193-0.806, P = 0.009, suggesting these strains are less capable of extra-pulmonary dissemination than others in the study population. We also found that individuals with the C allele of TLR-2 T597C allele were more likely to have tuberculosis caused by the East-Asian/Beijing genotype (OR = 1.57 [95% C.I. 1.15-2.15] than other individuals. The study provides evidence that M. tuberculosis genotype influences clinical disease phenotype and demonstrates, for the first time, a significant interaction between host and bacterial genotypes and the development of tuberculosis.

The impact of Fusarium mycotoxins on human and animal host susceptibility to infectious diseases.

Science.gov (United States)

Antonissen, Gunther; Martel, An; Pasmans, Frank; Ducatelle, Richard; Verbrugghe, Elin; Vandenbroucke, Virginie; Li, Shaoji; Haesebrouck, Freddy; Van Immerseel, Filip; Croubels, Siska

2014-01-28

Contamination of food and feed with mycotoxins is a worldwide problem. At present, acute mycotoxicosis caused by high doses is rare in humans and animals. Ingestion of low to moderate amounts of Fusarium mycotoxins is common and generally does not result in obvious intoxication. However, these low amounts may impair intestinal health, immune function and/or pathogen fitness, resulting in altered host pathogen interactions and thus a different outcome of infection. This review summarizes the current state of knowledge about the impact of Fusarium mycotoxin exposure on human and animal host susceptibility to infectious diseases. On the one hand, exposure to deoxynivalenol and other Fusarium mycotoxins generally exacerbates infections with parasites, bacteria and viruses across a wide range of animal host species. Well-known examples include coccidiosis in poultry, salmonellosis in pigs and mice, colibacillosis in pigs, necrotic enteritis in poultry, enteric septicemia of catfish, swine respiratory disease, aspergillosis in poultry and rabbits, reovirus infection in mice and Porcine Reproductive and Respiratory Syndrome Virus infection in pigs. However, on the other hand, T-2 toxin has been shown to markedly decrease the colonization capacity of Salmonella in the pig intestine. Although the impact of the exposure of humans to Fusarium toxins on infectious diseases is less well known, extrapolation from animal models suggests possible exacerbation of, for instance, colibacillosis and salmonellosis in humans, as well.

Infectious Bursal Disease Virus-Host Interactions: Multifunctional Viral Proteins that Perform Multiple and Differing Jobs

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Yao Qin

2017-01-01

Full Text Available Infectious bursal disease (IBD is an acute, highly contagious and immunosuppressive poultry disease caused by IBD virus (IBDV. The consequent immunosuppression increases susceptibility to other infectious diseases and the risk of subsequent vaccination failure as well. Since the genome of IBDV is relatively small, it has a limited number of proteins inhibiting the cellular antiviral responses and acting as destroyers to the host defense system. Thus, these virulence factors must be multifunctional in order to complete the viral replication cycle in a host cell. Insights into the roles of these viral proteins along with their multiple cellular targets in different pathways will give rise to a rational design for safer and effective vaccines. Here we summarize the recent findings that focus on the virus–cell interactions during IBDV infection at the protein level.

Host genetics and outcome in meningococcal disease: a systematic review and meta-analysis

NARCIS (Netherlands)

Brouwer, Matthijs C.; Read, Robert C.; van de Beek, Diederik

2010-01-01

Various genes regulate the intensity of the inflammatory and coagulation response to infection and therefore might determine the severity and outcome of meningococcal disease. We systematically reviewed the published work for case control studies on the influence of host genetics on severity and

A model to estimate effects of SNPs on host susceptibility and infectivity for an endemic infectious disease

NARCIS (Netherlands)

Biemans, Floor; Jong, de Mart C.M.; Bijma, Piter

2017-01-01

Background: Infectious diseases in farm animals affect animal health, decrease animal welfare and can affect human health. Selection and breeding of host individuals with desirable traits regarding infectious diseases can help to fight disease transmission, which is affected by two types of

Gut Microbiota and Host Reaction in Liver Diseases

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Hiroshi Fukui

2015-10-01

Full Text Available Although alcohol feeding produces evident intestinal microbial changes in animals, only some alcoholics show evident intestinal dysbiosis, a decrease in Bacteroidetes and an increase in Proteobacteria. Gut dysbiosis is related to intestinal hyperpermeability and endotoxemia in alcoholic patients. Alcoholics further exhibit reduced numbers of the beneficial Lactobacillus and Bifidobacterium. Large amounts of endotoxins translocated from the gut strongly activate Toll-like receptor 4 in the liver and play an important role in the progression of alcoholic liver disease (ALD, especially in severe alcoholic liver injury. Gut microbiota and bacterial endotoxins are further involved in some of the mechanisms of nonalcoholic fatty liver disease (NAFLD and its progression to nonalcoholic steatohepatitis (NASH. There is experimental evidence that a high-fat diet causes characteristic dysbiosis of NAFLD, with a decrease in Bacteroidetes and increases in Firmicutes and Proteobacteria, and gut dysbiosis itself can induce hepatic steatosis and metabolic syndrome. Clinical data support the above dysbiosis, but the details are variable. Intestinal dysbiosis and endotoxemia greatly affect the cirrhotics in relation to major complications and prognosis. Metagenomic approaches to dysbiosis may be promising for the analysis of deranged host metabolism in NASH and cirrhosis. Management of dysbiosis may become a cornerstone for the future treatment of liver diseases.

Host Factors and Biomarkers Associated with Poor Outcomes in Adults with Invasive Pneumococcal Disease.

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Shigeo Hanada

Full Text Available Invasive pneumococcal disease (IPD causes considerable morbidity and mortality. We aimed to identify host factors and biomarkers associated with poor outcomes in adult patients with IPD in Japan, which has a rapidly-aging population.In a large-scale surveillance study of 506 Japanese adults with IPD, we investigated the role of host factors, disease severity, biomarkers based on clinical laboratory data, treatment regimens, and bacterial factors on 28-day mortality.Overall mortality was 24.1%, and the mortality rate increased from 10.0% in patients aged ˂50 years to 33.1% in patients aged ≥80 years. Disease severity also increased 28-day mortality, from 12.5% among patients with bacteraemia without sepsis to 35.0% in patients with severe sepsis and 56.9% with septic shock. The death rate within 48 hours after admission was high at 54.9%. Risk factors for mortality identified by multivariate analysis were as follows: white blood cell (WBC count <4000 cells/μL (odds ratio [OR], 6.9; 95% confidence interval [CI], 3.7-12.8, p < .001; age ≥80 years (OR, 6.5; 95% CI, 2.0-21.6, p = .002; serum creatinine ≥2.0 mg/dL (OR, 4.5; 95% CI, 2.5-8.1, p < .001; underlying liver disease (OR, 3.5; 95% CI, 1.6-7.8, p = .002; mechanical ventilation (OR, 3.0; 95% CI, 1.7-5.6, p < .001; and lactate dehydrogenase ≥300 IU/L (OR, 2.4; 95% CI, 1.4-4.0, p = .001. Pneumococcal serotype and drug resistance were not associated with poor outcomes.Host factors, disease severity, and biomarkers, especially WBC counts and serum creatinine, were more important determinants of mortality than bacterial factors.

Use of the National Institutes of Health Consensus Guidelines Improves the Diagnostic Sensitivity of Gastrointestinal Graft-Versus-Host Disease.

Science.gov (United States)

Cardona, Diana M; Detweiler, Claire J; Shealy, Michael J; Sung, Anthony D; Wild, Daniel M; Poleski, Martin H; Balmadrid, Bryan L; Cirrincione, Constance T; Howell, David N; Sullivan, Keith M

2018-04-26

- Graft-versus-host disease of the gastrointestinal tract is a common complication of hematopoietic stem cell transplant associated with significant morbidity and mortality. Accurate diagnosis can be difficult and is a truly clinicopathologic endeavor. - To assess the diagnostic sensitivity of gastrointestinal graft-versus-host disease using the 2015 National Institutes of Health (NIH) histology consensus guidelines and to analyze histologic findings that support the guidelines. - Patients with allogeneic hematopoietic stem cell transplants were identified via a retrospective search of our electronic medical record from January 1, 2005, to January 1, 2011. Endoscopies with available histology were reviewed by 2 pathologists using the 2015 NIH guidelines. The clinical diagnosis was used as the gold standard. A nontransplant set of endoscopic biopsies was used as a control. - Of the 250 total endoscopies, 217 (87%) had a clinical diagnosis of gastrointestinal graft-versus-host disease. Use of the NIH consensus guidelines showed a sensitivity of 86% and a specificity of 65%. Thirty-seven of 58 (64%) cases with an initial false-negative histopathologic diagnosis were diagnosed as graft-versus-host disease on our review. - Use of the NIH histology consensus guidelines results in a high sensitivity and specificity, thereby decreasing false-negatives. Additionally, use of the NIH guidelines aids in creating uniformity and diagnostic clarity. Correlation with clinical and laboratory findings is critical in evaluating the differential diagnosis and to avoid false-positives. As expected, increased apoptosis with decreased inflammation was associated with a pathologic diagnosis of graft-versus-host disease and supports the NIH guidelines.

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.

Animal salmonelloses: a brief review of “host adaptation and host specificity” of Salmonella spp.

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Grammato Evangelopoulou

2013-07-01

Full Text Available Salmonella enterica, the most pathogenic species of the genusSalmonella, includes more than 2,500 serovars, many of which are of great veterinary and medical significance. The emergence of food-borne pathogens, such as Salmonella spp., has increased knowledge about the mechanisms helping microorganisms to persist and spread within new host populations. It has also increased information about the properties they acquire for adapting in the biological environment of a new host. Thedifferences observed between serovars in their host preference and clinical manifestations are referred to as “serovar-host specificity” or “serovar-host adaptation”. The genus Salmonella, highly adaptive to vertebrate hosts, has many pathogenic serovars showing host specificity. Serovar Salmonella Typhi, causing disease to man and higher primates, is a good example of host specificity. Thus, understanding the mechanisms that Salmonella serovars use to overcome animal species' barriers or adapt to new hosts is also important for understanding the origins of any other infectious diseases or the emergence of new pathogens. In addition, molecular methods used to study the virulence determinants of Salmonella serovars, could also be used to model ways of studying the virulence determinants used by bacteria in general, when causing disease to a specific animal species

Prevalence, care-seeking, and health service utilization for non-communicable diseases among Syrian refugees and host communities in Lebanon.

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Doocy, Shannon; Lyles, Emily; Hanquart, Baptiste; Woodman, Michael

2016-01-01

Given the large burden of non-communicable diseases (NCDs) among both Syrian refugees and the host communities within which they are settled, humanitarian actors and the government of Lebanon face immense challenges in addressing health needs. This study assessed health status, unmet needs, and utilization of health services among Syrian refugees and host communities in Lebanon. A cross-sectional survey of Syrian refugees and host communities in Lebanon was conducted using a two-stage cluster survey design with probability proportional to size sampling. To obtain information on chronic NCDs, respondents were asked a series of questions about hypertension, cardiovascular disease, diabetes, chronic respiratory disease, and arthritis. Differences in household characteristics by care-seeking for these conditions were examined using chi-square, t-test, and adjusted logistic regression methods. Over half (50.4 %) of refugee and host community households (60.2 %) reported a member with one of the five NCDs. Host community prevalence rates were significantly higher than refugees for all conditions except chronic respiratory diseases ( p  = 0.08). Care-seeking for NCDs among refugees and host community households was high across all conditions with 82.9 and 97.8 %, respectively, having sought care in Lebanon for their condition. Refugees utilized primary health care centers (PHCC) (57.7 %) most often while host communities sought care most in private clinics (62.4 %). Overall, 69.7 % of refugees and 82.7 % of host community members reported an out-of-pocket consultation payment ( p  = 0.041) with an average payment of US$15 among refugees and US$42 for the host community ( p Syrian crisis and the burden on the Lebanese health system, implications for both individuals with NCDs and Lebanon's health system are immense. The burden of out of pocket expenses on persons with NCDs are also substantial, especially given the tenuous economic status of many refugees

How host regulation of Helicobacter pylori-induced gastritis protects against peptic ulcer disease and gastric cancer.

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Dhar, Poshmaal; Ng, Garrett Z; Sutton, Philip

2016-09-01

The bacterial pathogen Helicobacter pylori is the etiological agent of a range of gastrointestinal pathologies including peptic ulcer disease and the major killer, gastric adenocarcinoma. Infection with this bacterium induces a chronic inflammatory response in the gastric mucosa (gastritis). It is this gastritis that, over decades, eventually drives the development of H. pylori-associated disease in some individuals. The majority of studies investigating H. pylori pathogenesis have focused on factors that promote disease development in infected individuals. However, an estimated 85% of those infected with H. pylori remain completely asymptomatic, despite the presence of pathogenic bacteria that drive a chronic gastritis that lasts many decades. This indicates the presence of highly effective regulatory processes in the host that, in most cases, keeps a check on inflammation and protect against disease. In this minireview we discuss such known host factors and how they prevent the development of H. pylori-associated pathologies. Copyright © 2016 the American Physiological Society.

Echinococcus multilocularis and Its Intermediate Host: A Model of Parasite-Host Interplay

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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.

The role of Ixodes scapularis, Borrelia burgdorferi and wildlife hosts in Lyme disease prevalence: A quantitative review.

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Halsey, Samniqueka J; Allan, Brian F; Miller, James R

2018-04-16

Due to the ongoing expansion of Ixodes scapularis (blacklegged tick) throughout the northeastern and midwestern United States, there is need to identify the role wildlife hosts play in the establishment and maintenance of tick populations. To quantify and synthesize the patterns of I. scapularis and Borrelia burgdorferi sensu stricto and sensu lato prevalence relative to wildlife hosts, we reviewed the findings of independent studies conducted throughout the United States. We performed a comprehensive literature search from 1970 to 2017 using the ISS Web of Science Core Collection and the keywords "Ixodes scapularis," "Ixodes dammini" and "Borrelia burgdorferi." We identified 116 studies for inclusion in our meta-analysis, with 187,414 individual wildlife hosts captured and examined for I. scapularis and either the host or ticks collected subsequently tested for B. burgdorferi. We found that only 13% of the wildlife mammals sampled comprised species other than Odocoileus virginianus (white-tailed deer) and Peromyscus leucopus (white-footed mouse). To examine whether there were regional differences between the Northeast, Midwest and the Southeast U.S. in I. scapularis infestation rates on wildlife hosts, we used general linear models (glm), with post hoc pairwise comparisons. In most cases, detection of I. scapularis and B. burgdorferi was significantly higher in the Northeast than the Midwest. Using data on host-specific I. scapularis infestation prevalence, B. burgdorferi prevalence in feeding larvae, and host permissiveness, we developed an epizootiological model to determine the relative contributions of individual hosts to B. burgdorferi-infected nymphs. Our model provides additional evidence that wildlife hosts other than P. leucopus may contribute more to Lyme disease risk than commonly thought. To aid in understanding the ecology of Lyme disease, we propose that additional studies sample non-Peromyscus spp. hosts to obtain more detailed tick and pathogen

Research Strategies to Reduce Tick Densities and the Risk of Tick-borne Disease Transmission through Host-Targeted Control

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While white-tailed deer are not reservoir hosts for the Lyme disease agent, Borrelia burgdorferi, they are the keystone host animal on which adult female blacklegged ticks engorge on blood that is essential to production of tick eggs and completion of the life cycle. This session explores current re...

Predators indirectly control vector-borne disease: linking predator-prey and host-pathogen models.

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Moore, Sean M; Borer, Elizabeth T; Hosseini, Parviez R

2010-01-06

Pathogens transmitted by arthropod vectors are common in human populations, agricultural systems and natural communities. Transmission of these vector-borne pathogens depends on the population dynamics of the vector species as well as its interactions with other species within the community. In particular, predation may be sufficient to control pathogen prevalence indirectly via the vector. To examine the indirect effect of predators on vectored-pathogen dynamics, we developed a theoretical model that integrates predator-prey and host-pathogen theory. We used this model to determine whether predation can prevent pathogen persistence or alter the stability of host-pathogen dynamics. We found that, in the absence of predation, pathogen prevalence in the host increases with vector fecundity, whereas predation on the vector causes pathogen prevalence to decline, or even become extinct, with increasing vector fecundity. We also found that predation on a vector may drastically slow the initial spread of a pathogen. The predator can increase host abundance indirectly by reducing or eliminating infection in the host population. These results highlight the importance of studying interactions that, within the greater community, may alter our predictions when studying disease dynamics. From an applied perspective, these results also suggest situations where an introduced predator or the natural enemies of a vector may slow the rate of spread of an emerging vector-borne pathogen.

Comparative genetic diversity of Lyme disease bacteria in Northern Californian ticks and their vertebrate hosts.

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Swei, Andrea; Bowie, Verna C; Bowie, Rauri C K

2015-04-01

Vector-borne pathogens are transmitted between vertebrate hosts and arthropod vectors, two immensely different environments for the pathogen. There is further differentiation among vertebrate hosts that often have complex, species-specific immunological responses to the pathogen. All this presents a heterogeneous environmental and immunological landscape with possible consequences on the population genetic structure of the pathogen. We evaluated the differential genetic diversity of the Lyme disease pathogen, Borrelia burgdorferi, in its vector, the western black-legged tick (Ixodes pacificus), and in its mammal host community using the 5S-23S rRNA intergenic spacer region. We found differences in haplotype distribution of B. burgdorferi in tick populations from two counties in California as well as between a sympatric tick and vertebrate host community. In addition, we found that three closely related haplotypes consistently occurred in high frequency in all sample types. Lastly, our study found lower species diversity of the B. burgdorferi species complex, known as B. burgdorferi sensu lato, in small mammal hosts versus the tick populations in a sympatric study area. Copyright © 2015 Elsevier GmbH. All rights reserved.

The interplay between intestinal bacteria and host metabolism in health and disease: lessons from Drosophila melanogaster

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Adam C. N. Wong

2016-03-01

Full Text Available All higher organisms negotiate a truce with their commensal microbes and battle pathogenic microbes on a daily basis. Much attention has been given to the role of the innate immune system in controlling intestinal microbes and to the strategies used by intestinal microbes to overcome the host immune response. However, it is becoming increasingly clear that the metabolisms of intestinal microbes and their hosts are linked and that this interaction is equally important for host health and well-being. For instance, an individual's array of commensal microbes can influence their predisposition to chronic metabolic diseases such as diabetes and obesity. A better understanding of host–microbe metabolic interactions is important in defining the molecular bases of these disorders and could potentially lead to new therapeutic avenues. Key advances in this area have been made using Drosophila melanogaster. Here, we review studies that have explored the impact of both commensal and pathogenic intestinal microbes on Drosophila carbohydrate and lipid metabolism. These studies have helped to elucidate the metabolites produced by intestinal microbes, the intestinal receptors that sense these metabolites, and the signaling pathways through which these metabolites manipulate host metabolism. Furthermore, they suggest that targeting microbial metabolism could represent an effective therapeutic strategy for human metabolic diseases and intestinal infection.

Genetic stability of foot-and-mouth disease virus during long-term infections in natural hosts.

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Ramirez-Carvajal, Lisbeth; Pauszek, Steven J; Ahmed, Zaheer; Farooq, Umer; Naeem, Khalid; Shabman, Reed S; Stockwell, Timothy B; Rodriguez, Luis L

2018-01-01

Foot-and-mouth disease (FMD) is a severe infection caused by a picornavirus that affects livestock and wildlife. Persistence in ruminants is a well-documented feature of Foot-and-mouth disease virus (FMDV) pathogenesis and a major concern for disease control. Persistently infected animals harbor virus for extended periods, providing a unique opportunity to study within-host virus evolution. This study investigated the genetic dynamics of FMDV during persistent infections of naturally infected Asian buffalo. Using next-generation sequencing (NGS) we obtained 21 near complete FMDV genome sequences from 12 sub-clinically infected buffalo over a period of one year. Four animals yielded only one virus isolate and one yielded two isolates of different serotype suggesting a serial infection. Seven persistently infected animals yielded more than one virus of the same serotype showing a long-term intra-host viral genetic divergence at the consensus level of less than 2.5%. Quasi-species analysis showed few nucleotide variants and non-synonymous substitutions of progeny virus despite intra-host persistence of up to 152 days. Phylogenetic analyses of serotype Asia-1 VP1 sequences clustered all viruses from persistent animals with Group VII viruses circulating in Pakistan in 2011, but distinct from those circulating on 2008-2009. Furthermore, signature amino acid (aa) substitutions were found in the antigenically relevant VP1 of persistent viruses compared with viruses from 2008-2009. Intra-host purifying selective pressure was observed, with few codons in structural proteins undergoing positive selection. However, FMD persistent viruses did not show a clear pattern of antigenic selection. Our findings provide insight into the evolutionary dynamics of FMDV populations within naturally occurring subclinical and persistent infections that may have implications to vaccination strategies in the region.

Genetic stability of foot-and-mouth disease virus during long-term infections in natural hosts.

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Lisbeth Ramirez-Carvajal

Full Text Available Foot-and-mouth disease (FMD is a severe infection caused by a picornavirus that affects livestock and wildlife. Persistence in ruminants is a well-documented feature of Foot-and-mouth disease virus (FMDV pathogenesis and a major concern for disease control. Persistently infected animals harbor virus for extended periods, providing a unique opportunity to study within-host virus evolution. This study investigated the genetic dynamics of FMDV during persistent infections of naturally infected Asian buffalo. Using next-generation sequencing (NGS we obtained 21 near complete FMDV genome sequences from 12 sub-clinically infected buffalo over a period of one year. Four animals yielded only one virus isolate and one yielded two isolates of different serotype suggesting a serial infection. Seven persistently infected animals yielded more than one virus of the same serotype showing a long-term intra-host viral genetic divergence at the consensus level of less than 2.5%. Quasi-species analysis showed few nucleotide variants and non-synonymous substitutions of progeny virus despite intra-host persistence of up to 152 days. Phylogenetic analyses of serotype Asia-1 VP1 sequences clustered all viruses from persistent animals with Group VII viruses circulating in Pakistan in 2011, but distinct from those circulating on 2008-2009. Furthermore, signature amino acid (aa substitutions were found in the antigenically relevant VP1 of persistent viruses compared with viruses from 2008-2009. Intra-host purifying selective pressure was observed, with few codons in structural proteins undergoing positive selection. However, FMD persistent viruses did not show a clear pattern of antigenic selection. Our findings provide insight into the evolutionary dynamics of FMDV populations within naturally occurring subclinical and persistent infections that may have implications to vaccination strategies in the region.

Estimating Coextinction Risks from Epidemic Tree Death: Affiliate Lichen Communities among Diseased Host Tree Populations of Fraxinus excelsior

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Jönsson, Mari T.; Thor, Göran

2012-01-01

At least 10% of the world’s tree species are threatened with extinction and pathogens are increasingly implicated in tree threats. Coextinction and threats to affiliates as a consequence of the loss or decline of their host trees is a poorly understood phenomenon. Ash dieback is an emerging infectious disease causing severe dieback of common ash Fraxinus excelsior throughout Europe. We utilized available empirical data on affiliate epiphytic lichen diversity (174 species and 17,800 observations) among 20 ash dieback infected host tree populations of F. excelsior on the island Gotland in the Baltic Sea, Sweden. From this, we used structured scenario projections scaled with empirical data of ash dieback disease to generate probabilistic models for estimating local and regional lichen coextinction risks. Average coextinction probabilities (Ā) were 0.38 (95% CI ±0.09) for lichens occurring on F. excelsior and 0.14 (95% CI ±0.03) when considering lichen persistence on all tree species. Ā was strongly linked to local disease incidence levels and generally increasing with lichen host specificity to F. excelsior and decreasing population size. Coextinctions reduced affiliate community viability, with significant local reductions in species richness and shifts in lichen species composition. Affiliates were projected to become locally extirpated before their hosts, illuminating the need to also consider host tree declines. Traditionally managed open wooded meadows had the highest incidence of ash dieback disease and significantly higher proportions of affiliate species projected to go extinct, compared with unmanaged closed forests and semi-open grazed sites. Most cothreatened species were not previously red-listed, which suggest that tree epidemics cause many unforeseen threats to species. Our analysis shows that epidemic tree deaths represent an insidious, mostly overlooked, threat to sessile affiliate communities in forested environments. Current conservation and

Emerging technologies for oral diagnostics: lessons from chronic graft-versus-host disease

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Mays, Jacqueline W.; Ambatipudi, Kiran S.; Bassim, Carol W.; Melvin, James E.

2013-05-01

Saliva is a protein-rich oral fluid that contains information about systemic and oral-specific disease pathogenesis and diagnosis. Technologies are emerging to improve detection of protein components of human saliva for use not only in biomarker discovery, but also for the illumination of pathways involved in oral disease. These include the optimization of liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) analysis of saliva in health and disease. Downstream of saliva component identification and validation comes the complex task of connecting salivary proteomic data to biological function, disease state, and other clinical patient information in a meaningful way. Augmentation of database information with biological expertise is crucial for effective analysis of potential biomarkers and disease pathways in order to improve diagnosis and identify putative therapeutic targets. This presentation will use LC-MS/MS analysis of saliva from chronic Graft-versus-Host disease (cGVHD) patients to illustrate these principles, and includes a discussion of the complex clinical and diagnostic issues related to proteomics and biomarker research in cGVHD.

Relevance of genetically determined host factors to the prognosis of meningococcal disease.

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Domingo, P; Muñiz-Diaz, E; Baraldès, M A; Arilla, M; Barquet, N; Pericas, R; Juárez, C; Madoz, P; Vázquez, G

2004-08-01

To assess the relevance of genetically determined host factors for the prognosis of meningococcal disease, Fc gamma receptor IIA (FcgammaRIIA), the tumor necrosis factor alpha (TNF-alpha) gene promoter region, and plasminogen-activator-inhibitor-1 (PAI-1) gene polymorphisms were studied in 145 patients with meningococcal disease and in 290 healthy controls matched by sex. Distribution of FcgammaRIIA, TNF-alpha, and PAI-1 alleles was not significantly different between patients and controls. Patients with the FcgammaRIIA-R/R 131 allotype scored > or =1 point in the Barcelona prognostic system more frequently than patients with other allotypes (odds ratio, 18.6; 95% confidence interval, 7.1-49.0, PFc gamma receptor IIA polymorphism was associated with markers of disease severity, but TNF-alpha and PAI-1 polymorphisms were not.

Salvaged allogeneic hematopoietic stem cell transplantation for pediatric chemotherapy refractory acute leukemia.

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Wang, Jingbo; Yuan, Lei; Cheng, Haoyu; Fei, Xinhong; Yin, Yumin; Gu, Jiangying; Xue, Song; He, Junbao; Yang, Fan; Wang, Xiaocan; Yang, Yixin; Zhang, Weijie

2018-01-09

There is an ongoing debate concerning the performance of salvaged allogeneic hematopoietic stem cell transplantation (allo-HSCT) in pediatric patients with acute refractory leukemia, in whom the prognosis is quite dismal. Few studies have ever been conducted on this subject. This may be partly due to missed opportunities by majority of the patients in such situations. To investigate the feasibility, evaluate the efficiency, and identify the prognostic factors of allo-HSCT in this sub-setting, the authors performed a single institution-based retrospective analysis. A total of 44 patients, of whom 28 had acute myeloid leukemia (AML), 13 had acute lymphocytic leukemia (ALL), and 3 had mixed phenotype leukemia (MPL), were enrolled in this study. With a median follow-up of 19 months, the estimated 2-year overall survival (OS) and progression free survival (PFS) were 34.3% (95% CI, 17.9-51.4%) and 33.6% (95% CI, 18.0-50.1%), respectively. The estimated 2-year incidence rates of relapse and non-relapse mortality (NRM) were 43.8% (95% CI 26.4-60.0%) and 19.6% (95% CI 9.1-32.9%), respectively. The estimated 100-day cumulative incidence of acute graft versus host disease (aGvHD) was 43.6% (95% CI 28.7-57.5%), and the 1-year cumulative incidence of chronic GvHD (cGvHD) was 45.5% (95% CI 30.5-59.3%). Compared with the previous studies, the multivariate analysis in this study additionally identified that female donors and cGvHD were associated with lower relapse and better PFS and OS. Male recipients, age younger than 10 years, a diagnosis of ALL, and the intermediate-adverse cytogenetic risk group were associated with increased relapse. On the contrary, extramedullary disease (EMD) and aGvHD were only linked to worse PFS. These data suggested that although only one-third of the patients would obtain PFS over 2 years, salvaged allo-HSCT is still the most reliable and best therapeutic strategy for refractory pediatric acute leukemia. If probable, choosing a female donor, better

Host response mechanisms in periodontal diseases

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Nora SILVA

2015-06-01

Full Text Available Periodontal diseases usually refer to common inflammatory disorders known as gingivitis and periodontitis, which are caused by a pathogenic microbiota in the subgingival biofilm, including Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia and Treponema denticola that trigger innate, inflammatory, and adaptive immune responses. These processes result in the destruction of the tissues surrounding and supporting the teeth, and eventually in tissue, bone and finally, tooth loss. The innate immune response constitutes a homeostatic system, which is the first line of defense, and is able to recognize invading microorganisms as non-self, triggering immune responses to eliminate them. In addition to the innate immunity, adaptive immunity cells and characteristic cytokines have been described as important players in the periodontal disease pathogenesis scenario, with a special attention to CD4+ T-cells (T-helper cells. Interestingly, the T cell-mediated adaptive immunity development is highly dependent on innate immunity-associated antigen presenting cells, which after antigen capture undergo into a maturation process and migrate towards the lymph nodes, where they produce distinct patterns of cytokines that will contribute to the subsequent polarization and activation of specific T CD4+ lymphocytes. Skeletal homeostasis depends on a dynamic balance between the activities of the bone-forming osteoblasts (OBLs and bone-resorbing osteoclasts (OCLs. This balance is tightly controlled by various regulatory systems, such as the endocrine system, and is influenced by the immune system, an osteoimmunological regulation depending on lymphocyte- and macrophage-derived cytokines. All these cytokines and inflammatory mediators are capable of acting alone or in concert, to stimulate periodontal breakdown and collagen destruction via tissue-derived matrix metalloproteinases, a characterization of the progression of periodontitis as

Host response mechanisms in periodontal diseases

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SILVA, Nora; ABUSLEME, Loreto; BRAVO, Denisse; DUTZAN, Nicolás; GARCIA-SESNICH, Jocelyn; VERNAL, Rolando; HERNÁNDEZ, Marcela; GAMONAL, Jorge

2015-01-01

Periodontal diseases usually refer to common inflammatory disorders known as gingivitis and periodontitis, which are caused by a pathogenic microbiota in the subgingival biofilm, including Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia and Treponema denticola that trigger innate, inflammatory, and adaptive immune responses. These processes result in the destruction of the tissues surrounding and supporting the teeth, and eventually in tissue, bone and finally, tooth loss. The innate immune response constitutes a homeostatic system, which is the first line of defense, and is able to recognize invading microorganisms as non-self, triggering immune responses to eliminate them. In addition to the innate immunity, adaptive immunity cells and characteristic cytokines have been described as important players in the periodontal disease pathogenesis scenario, with a special attention to CD4+ T-cells (T-helper cells). Interestingly, the T cell-mediated adaptive immunity development is highly dependent on innate immunity-associated antigen presenting cells, which after antigen capture undergo into a maturation process and migrate towards the lymph nodes, where they produce distinct patterns of cytokines that will contribute to the subsequent polarization and activation of specific T CD4+ lymphocytes. Skeletal homeostasis depends on a dynamic balance between the activities of the bone-forming osteoblasts (OBLs) and bone-resorbing osteoclasts (OCLs). This balance is tightly controlled by various regulatory systems, such as the endocrine system, and is influenced by the immune system, an osteoimmunological regulation depending on lymphocyte- and macrophage-derived cytokines. All these cytokines and inflammatory mediators are capable of acting alone or in concert, to stimulate periodontal breakdown and collagen destruction via tissue-derived matrix metalloproteinases, a characterization of the progression of periodontitis as a stage that

Unraveling the Mechanisms of Cutaneous Graft-Versus-Host Disease

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Pedro Santos e Sousa

2018-05-01

Full Text Available The skin is the most common target organ affected by graft-versus-host disease (GVHD, with severity and response to therapy representing important predictors of patient survival. Although many of the initiating events in GVHD pathogenesis have been defined, less is known about why treatment resistance occurs or why there is often a permanent failure to restore tissue homeostasis. Emerging data suggest that the unique immune microenvironment in the skin is responsible for defining location- and context-specific mechanisms of injury that are distinct from those involved in other target organs. In this review, we address recent advances in our understanding of GVHD biology in the skin and outline the new research themes that will ultimately enable design of precision therapies.

Does canine inflammatory bowel disease influence gut microbial profile and host metabolism?

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Xu, Jia; Verbrugghe, Adronie; Lourenço, Marta; Janssens, Geert P J; Liu, Daisy J X; Van de Wiele, Tom; Eeckhaut, Venessa; Van Immerseel, Filip; Van de Maele, Isabel; Niu, Yufeng; Bosch, Guido; Junius, Greet; Wuyts, Brigitte; Hesta, Myriam

2016-06-16

Inflammatory bowel disease (IBD) refers to a diverse group of chronic gastrointestinal diseases, and gut microbial dysbiosis has been proposed as a modulating factor in its pathogenesis. Several studies have investigated the gut microbial ecology of dogs with IBD but it is yet unclear if this microbial profile can alter the nutrient metabolism of the host. The aim of the present study was to characterize the faecal bacterial profile and functionality as well as to determine host metabolic changes in IBD dogs. Twenty-three dogs diagnosed with IBD and ten healthy control dogs were included. Dogs with IBD were given a clinical score using the canine chronic enteropathy clinical activity index (CCECAI). Faecal short-chain fatty acids (SCFA) and ammonia concentrations were measured and quantitative PCR was performed. The concentration of plasma amino acids, acylcarnitines, serum folate, cobalamin, and indoxyl sulfate was determined. No significant differences in the abundance of a selection of bacterial groups and fermentation metabolites were observed between the IBD and control groups. However, significant negative correlations were found between CCECAI and the faecal proportion of Lactobacillus as well as between CCECAI and total SCFA concentration. Serum folate and plasma citrulline were decreased and plasma valine was increased in IBD compared to control dogs. Increased plasma free carnitine and total acylcarnitines were observed in IBD compared with control dogs, whereas short-chain acylcarnitines (butyrylcarnitine + isobutyrylcarnitine and, methylmalonylcarnitine) to free carnitine ratios decreased. Dogs with IBD had a higher 3-hydroxyisovalerylcarnitine + isovalerylcarnitine to leucine ratio compared to control dogs. Canine IBD induced a wide range of changes in metabolic profile, especially for the plasma concentrations of short-chain acylcarnitines and amino acids, which could have evolved from tissue damage and alteration in host metabolism. In

Multifunctional roles of leader protein of foot-and-mouth disease viruses in suppressing host antiviral responses.

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Liu, Yingqi; Zhu, Zixiang; Zhang, Miaotao; Zheng, Haixue

2015-10-28

Foot-and-mouth disease virus (FMDV) leader protein (L(pro)) is a papain-like proteinase, which plays an important role in FMDV pathogenesis. L(pro) exists as two forms, Lab and Lb, due to translation being initiated from two different start codons separated by 84 nucleotides. L(pro) self-cleaves from the nascent viral polyprotein precursor as the first mature viral protein. In addition to its role as a viral proteinase, L(pro) also has the ability to antagonize host antiviral effects. To promote FMDV replication, L(pro) can suppress host antiviral responses by three different mechanisms: (1) cleavage of eukaryotic translation initiation factor 4 γ (eIF4G) to shut off host protein synthesis; (2) inhibition of host innate immune responses through restriction of interferon-α/β production; and (3) L(pro) can also act as a deubiquitinase and catalyze deubiquitination of innate immune signaling molecules. In the light of recent functional and biochemical findings regarding L(pro), this review introduces the basic properties of L(pro) and the mechanisms by which it antagonizes host antiviral responses.

Use of lymphokine-activated killer cells to prevent bone marrow graft rejection and lethal graft-vs-host disease

International Nuclear Information System (INIS)

Azuma, E.; Yamamoto, H.; Kaplan, J.

1989-01-01

Prompted by our recent finding that lymphokine-activated killer (LAK) cells mediate both veto and natural suppression, we tested the ability of adoptively transferred LAK cells to block two in vivo alloreactions which complicate bone marrow transplantation: resistance to transplanted allogeneic bone marrow cells, and lethal graft-vs-host disease. Adoptive transfer of either donor type B6D2 or recipient-type B6 lymphokine-activated bone marrow cells, cells found to have strong LAK activity, abrogated or inhibited the resistance of irradiated B6 mice to both B6D2 marrow and third party-unrelated C3H marrow as measured by CFU in spleen on day 7. The ability of lymphokine-activated bone marrow cells to abrogate allogeneic resistance was eliminated by C lysis depletion of cells expressing asialo-GM1, NK1.1, and, to a variable degree, Thy-1, but not by depletion of cells expressing Lyt-2, indicating that the responsible cells had a LAK cell phenotype. Similar findings were obtained by using splenic LAK cells generated by 3 to 7 days of culture with rIL-2. Demonstration that allogeneic resistance could be blocked by a cloned LAK cell line provided direct evidence that LAK cells inhibit allogeneic resistance. In addition to inhibiting allogeneic resistance, adoptively transferred recipient-type LAK cells prevented lethal graft-vs-host disease, and permitted long term engraftment of allogeneic marrow. Irradiation prevented LAK cell inhibition of both allogeneic resistance and lethal graft-vs-host disease. These findings suggest that adoptive immunotherapy with LAK cells may prove useful in preventing graft rejection and graft-versus-host disease in human bone marrow transplant recipients

The Role of Programmed Cell Death Ligand-1 (PD-L1/CD274) in the Development of Graft versus Host Disease

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Al-Chaqmaqchi, Heevy; Sadeghi, Behnam; Abedi-Valugerdi, Manuchehr; Al-Hashmi, Sulaiman; Fares, Mona; Kuiper, Raoul; Lundahl, Joachim

2013-01-01

Programmed cell death ligand-1 (PD-L1/CD274) is an immunomodulatory molecule involved in cancer and complications of bone marrow transplantation, such as graft rejection and graft-versus-host disease. The present study was designed to assess the dynamic expression of this molecule after hematopoietic stem cell transplantation in relation to acute graft-versus-host disease. Female BALB/c mice were conditioned with busulfan and cyclophosphamide and transplanted with either syngeneic or allogeneic (male C57BL/6 mice) bone marrow and splenic cells. The expression of PD-L1 was evaluated at different time points employing qPCR, western blot and immunohistochemistry. Allogeneic- but not syngeneic-transplanted animals exhibited a marked up-regulation of PD-L1 expression in the muscle and kidney, but not the liver, at days 5 and 7 post transplantation. In mice transplanted with allogeneic bone marrow cells, the enhanced expression of PD-L1 was associated with high serum levels of IFNγ and TNFα at corresponding intervals. Our findings demonstrate that PD-L1 is differently induced and expressed after allogeneic transplantation than it is after syngeneic transplantation, and that it is in favor of target rather than non-target organs at the early stages of acute graft-versus-host disease. This is the first study to correlate the dynamics of PD-L1 at the gene-, protein- and activity levels with the early development of acute graft-versus-host disease. Our results suggest that the higher expression of PD-L1 in the muscle and kidney (non-target tissues) plays a protective role in skeletal muscle during acute graft-versus-host disease. PMID:23593203

Graft irradiation abrogates graft-versus-host disease in combined pancreas-spleen transplantation

International Nuclear Information System (INIS)

Schulak, J.A.; Sharp, W.J.

1986-01-01

A model of combined pancreas-spleen transplantation (PST) was studied in LBN F1 recipients of Lewis grafts in order to evaluate the efficacy of pretransplant graft irradiation in preventing lethal graft-versus-host disease (GVHD). Recipients of unmodified PST uniformly developed severe GVHD and died (MST = 16.7 +/- 3.8 days). Whole body donor irradiation with either 500 or 250 rad prevented lethal GVHD. Similarly, ex vivo graft irradiation with either 1000 or 500 rad also resulted in normal weight gain, graft function, and host survival for the 6-week study period. Conversely, delay of graft irradiation until 3 days after transplantation failed to prevent this complication (MST = 15.8 +/- 3.7 days). Recipients of irradiated grafts displayed glucose tolerance tests that were identical to those in the control group indicating that the doses of radiation employed in these experiments were not deleterious to islet function. Irradiated spleen grafts appeared histologically normal at 6 weeks after transplantation. Cells derived from these grafts failed to stimulate lymph node enlargement in a popliteal lymph node assay for GVHD, suggesting that these spleens may have become repopulated with host cells. These experiments confirm that PST has the potential to cause lethal GVHD and suggest that pretransplant graft irradiation may be used to prevent its occurrence

Higher CD3(+) and CD34(+) cell doses in the graft increase the incidence of acute GVHD in children receiving BMT for thalassemia.

Science.gov (United States)

Gaziev, J; Isgrò, A; Marziali, M; Daniele, N; Gallucci, C; Sodani, P; Simone, M D; Adorno, G; Paciaroni, K; Andreani, M; Lanti, A; Del Proposto, G; Testi, M; De Angelis, G; Roveda, A; Alfieri, C; Saltarelli, F; Lucarelli, G

2012-01-01

We evaluated the incidence of GVHD, risk factors and the impact of graft composition on acute GVHD (aGVHD) in 92 children who underwent BMT for thalassemia following busulfan/cyclophosphamide (BUCY)-based conditioning regimens and GVHD prophylaxis with CSA/short-MTX and methylprednisolone. The incidence of grade 2-4 and 3-4 aGVHD was 35% (95% confidence interval (CI) 25-44) and 9% (95% CI 4-16), respectively. We found that CD3(+) and CD34(+) cell doses above the median were associated with high incidence of grade 2-4 aGVHD (49 vs 20%, P=0.005 and 46 vs 23%, P=0.021, respectively). In multivariate analysis, high CD3(+) (hazard ratio (HR) 4.6; 95% CI 1.4-14.7; P=0.010) and CD34(+) (HR 4.3; 95% CI 1.4-12.7; P=0.011) cell doses were associated with grade 2-4 aGVHD. We further examined the effect of CD3(+) and CD34(+) cell doses on aGVHD using quartile cutoff points and found a minimum threshold for CD3(+) (38 × 10(6)/kg) and CD34(+) (4 × 10(6)/kg) cells above which the incidence of grade 2-4 aGVHD is significantly increased. This study shows for the first time a positive correlation between the number of CD3(+) and CD34(+) cells and aGVHD in children receiving sibling BMT, and indicates that using tailored and more intensive post transplant immunosuppression may permit to better control aGVHD.

The Role of NLR-related Protein 3 Inflammasome in Host Defense and Inflammatory Diseases

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Chul-Su Yang

2012-03-01

Full Text Available Among a number of innate receptors, the nucleotide-binding domain leucine-rich repeat containing (NLR nucleotide oligomerization domain (NOD-like receptor families are involved in the recognition of cytosolic pathogen- or danger-associated molecules. Activation of these specific sets of receptors leads to the assembly of a multiprotein complex, the inflammasome, leading to the activation of caspase-1 and maturation of the cytokines interleukin (IL-1β, IL-18, and IL-33. Among NLRs, NLR-related protein 3 (NLRP3 is one of the best-characterized receptors that activates the inflammasome. There is no doubt that NLRP3 inflammasome activation is important for host defense and effective pathogen clearance against fungal, bacterial, and viral infection. In addition, mounting evidence indicates that the NLRP3 inflammasome plays a role in a variety of inflammatory diseases, including gout, atherosclerosis, and type II diabetes, as well as under conditions of cellular stress or injury. Here, we review recent advances in our understanding of the role of the NLRP3 inflammasome in host defense and various inflammatory diseases.

Scaling up from greenhouse resistance to fitness in the field for a host of an emerging forest disease

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Katherine J. Hayden; Matteo Garbelotto; Richard Dodd; Jessica W. Wright

2013-01-01

Forest systems are increasingly threatened by emergent, exotic diseases, yet management strategies for forest trees may be hindered by long generation times and scant background knowledge. We tested whether nursery disease resistance and growth traits have predictive value for the conservation of Notholithocarpus densiflorus, the host most...

Chronic graft-versus-host disease in the rat radiation chimera. III. Immunology and immunopathology in rapidly induced models

International Nuclear Information System (INIS)

Beschorner, W.E.; Tutschka, P.J.; Santos, G.W.

1983-01-01

Although chronic graft-versus-host disease (GVHD) frequently develops in the long-term rat radiation chimera, we present three additional models in which a histologically similar disease is rapidly induced. These include adoptive transfer of spleen and bone marrow from rats with spontaneous chronic GVHD into lethally irradiated rats of the primary host strain; sublethal irradiation of stable chimeras followed by a booster transplant; and transfer of spleen cells of chimeras recovering from acute GVHD into second-party (primary recipient strain) or third-party hosts. Some immunopathologic and immune abnormalities associated with spontaneous chronic GVHD were not observed in one or more of the induced models. Thus, IgM deposition in the skin, antinuclear antibodies, and vasculitis appear to be paraphenomena. On the other hand, lymphoid hypocellularity of the thymic medulla, immaturity of splenic follicles, and nonspecific suppressor cells were consistently present in the long term chimeras, and in all models. These abnormalities therefore may be pathogenetically important, or closely related to the development of chronic GVHD

The Role of B Cell Targeting in Chronic Graft-Versus-Host Disease

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Ruben Rhoades

2017-10-01

Full Text Available Chronic graft-versus-host disease (cGVHD is a leading cause of late morbidity and mortality following allogeneic stem cell transplantation. Current therapies, including corticosteroids and calcineurin inhibitors, are only effective in roughly 50% of cases; therefore, new treatment strategies are under investigation. What was previously felt to be a T cell disease has more recently been shown to involve activation of both T and B cells, as well as a number of cytokines. With a better understanding of its pathophysiology have come more expansive preclinical and clinical trials, many focused on B cell signaling. This report briefly reviews our current understanding of cGVHD pathophysiology and reviews clinical and preclinical trials with B cell-targeted agents.

Disease spread across multiple scales in a spatial hierarchy: effect of host spatial structure and of inoculum quantity and distribution.

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Gosme, Marie; Lucas, Philippe

2009-07-01

Spatial patterns of both the host and the disease influence disease spread and crop losses. Therefore, the manipulation of these patterns might help improve control strategies. Considering disease spread across multiple scales in a spatial hierarchy allows one to capture important features of epidemics developing in space without using explicitly spatialized variables. Thus, if the system under study is composed of roots, plants, and planting hills, the effect of host spatial pattern can be studied by varying the number of plants per planting hill. A simulation model based on hierarchy theory was used to simulate the effects of large versus small planting hills, low versus high level of initial infections, and aggregated versus uniform distribution of initial infections. The results showed that aggregating the initially infected plants always resulted in slower epidemics than spreading out the initial infections uniformly. Simulation results also showed that, in most cases, disease epidemics were slower in the case of large host aggregates (100 plants/hill) than with smaller aggregates (25 plants/hill), except when the initially infected plants were both numerous and spread out uniformly. The optimal strategy for disease control depends on several factors, including initial conditions. More importantly, the model offers a framework to account for the interplay between the spatial characteristics of the system, rates of infection, and aggregation of the disease.

MECHANISMS OF MICROBE-HOST-INTERACTION IN CROHN'S DISEASE: DYSBIOSIS VS. PATHOBIONT SELECTION

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Ludovica F. Buttó

2015-11-01

Full Text Available Crohn’s disease (CD is a systemic chronic inflammatory condition mainly characterized by discontinuous transmural pathology of the gastrointestinal tract and frequent extra-intestinal manifestations with intermittent episodes of remission and relapse. Genome-wide association studies identified a number of risk loci that, catalyzed by environmental triggers, result in the loss of tolerance towards commensal bacteria based on dysregulated innate effector functions and anti-microbial defense, leading to exacerbated adaptive immune responses responsible for chronic immune-mediated tissue damage. In this review, we discuss the interrelated role of changes in the intestinal microbiota, epithelial barrier integrity and immune cell functions on the pathogenesis of CD, describing the current approaches available to investigate the molecular mechanisms underlying the disease. Substantial effort has been dedicated to define disease-associated changes in the intestinal microbiota (dysbiosis and to link pathobionts to the aetiology of IBD. A cogent definition of dysbiosis is lacking, as well as an agreement of whether pathobionts or complex shifts in the microbiota trigger inflammation in the host. Among the rarely available animal models, SAMP/Yit and TNFdeltaARE mice are the best known displaying a transmural CD-like phenotype. New hypothesis-driven mouse models e.g. epithelial-specific Caspase8-/-, ATG16L1-/- and XBP-1-/- mice validate pathway-focused function of specific CD-associated risk genes highlighting the role of Paneth cells in antimicrobial defense. To study the causal role of bacteria in initiating inflammation in the host, the use of germfree mouse models is indispensable. Unraveling the interactions of genes, immune cells and microbes constitute a criterion for the development of safe, reliable and effective treatment options for CD.

Effect of Intermediate Hosts on Emerging Zoonoses.

Science.gov (United States)

Cui, Jing-An; Chen, Fangyuan; Fan, Shengjie

2017-08-01

Most emerging zoonotic pathogens originate from animals. They can directly infect humans through natural reservoirs or indirectly through intermediate hosts. As a bridge, an intermediate host plays different roles in the transmission of zoonotic pathogens. In this study, we present three types of pathogen transmission to evaluate the effect of intermediate hosts on emerging zoonotic diseases in human epidemics. These types are identified as follows: TYPE 1, pathogen transmission without an intermediate host for comparison; TYPE 2, pathogen transmission with an intermediate host as an amplifier; and TYPE 3, pathogen transmission with an intermediate host as a vessel for genetic variation. In addition, we established three mathematical models to elucidate the mechanisms underlying zoonotic disease transmission according to these three types. Stability analysis indicated that the existence of intermediate hosts increased the difficulty of controlling zoonotic diseases because of more difficult conditions to satisfy for the disease to die out. The human epidemic would die out under the following conditions: TYPE 1: [Formula: see text] and [Formula: see text]; TYPE 2: [Formula: see text], [Formula: see text], and [Formula: see text]; and TYPE 3: [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text] Simulation with similar parameters demonstrated that intermediate hosts could change the peak time and number of infected humans during a human epidemic; intermediate hosts also exerted different effects on controlling the prevalence of a human epidemic with natural reservoirs in different periods, which is important in addressing problems in public health. Monitoring and controlling the number of natural reservoirs and intermediate hosts at the right time would successfully manage and prevent the prevalence of emerging zoonoses in humans.

A mathematical modelling framework for linked within-host and between-host dynamics for infections with free-living pathogens in the environment.

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Garira, Winston; Mathebula, Dephney; Netshikweta, Rendani

2014-10-01

In this study we develop a mathematical modelling framework for linking the within-host and between-host dynamics of infections with free-living pathogens in the environment. The resulting linked models are sometimes called immuno-epidemiological models. However, there is still no generalised framework for linking the within-host and between-host dynamics of infectious diseases. Furthermore, for infections with free-living pathogens in the environment, there is an additional stumbling block in that there is a gap in knowledge on how environmental factors (through water, air, soil, food, fomites, etc.) alter many aspects of such infections including susceptibility to infective dose, persistence of infection, pathogen shedding and severity of the disease. In this work, we link the two subsystems (within-host and between-host models) by identifying the within-host and between-host variables and parameters associated with the environmental dynamics of the pathogen and then design a feedback of the variables and parameters across the within-host and between-host models using human schistosomiasis as a case study. We study the mathematical properties of the linked model and show that the model is epidemiologically well-posed. Using results from the analysis of the endemic equilibrium expression, the disease reproductive number R0, and numerical simulations of the full model, we adequately account for the reciprocal influence of the linked within-host and between-host models. In particular, we illustrate that for human schistosomiasis, the outcome of infection at the individual level determines if, when and how much the individual host will further transmit the infectious agent into the environment, eventually affecting the spread of the infection in the host population. We expect the conceptual modelling framework developed here to be applicable to many infectious disease with free-living pathogens in the environment beyond the specific disease system of human

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.

New mechanisms of disease and parasite-host interactions.

Science.gov (United States)

de Souza, Tiago Alves Jorge; de Carli, Gabriel Jose; Pereira, Tiago Campos

2016-09-01

An unconventional interaction between a patient and parasites was recently reported, in which parasitic cells invaded host's tissues, establishing several tumors. This finding raises various intriguing hypotheses on unpredicted forms of interplay between a patient and infecting parasites. Here we present four unusual hypothetical host-parasite scenarios with intriguing medical consequences. Relatively simple experimental designs are described in order to evaluate such hypotheses. The first one refers to the possibility of metabolic disorders in parasites intoxicating the host. The second one is on possibility of patients with inborn errors of metabolism (IEM) being more resistant to parasites (due to accumulation of toxic compounds in the bloodstream). The third one refers to a mirrored scenario: development of tumors in parasites due to ingestion of host's circulating cancer cells. The last one describes a complex relationship between parasites accumulating a metabolite and supplying it to a patient with an IEM. Copyright © 2016 Elsevier Ltd. All rights reserved.

Possible Relevance of Receptor-Receptor Interactions between Viral- and Host-Coded Receptors for Viral-Induced Disease

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Luigi F. Agnati

2007-01-01

Full Text Available It has been demonstrated that some viruses, such as the cytomegalovirus, code for G-protein coupled receptors not only to elude the immune system, but also to redirect cellular signaling in the receptor networks of the host cells. In view of the existence of receptor-receptor interactions, the hypothesis is introduced that these viral-coded receptors not only operate as constitutively active monomers, but also can affect other receptor function by interacting with receptors of the host cell. Furthermore, it is suggested that viruses could also insert not single receptors (monomers, but clusters of receptors (receptor mosaics, altering the cell metabolism in a profound way. The prevention of viral receptor-induced changes in host receptor networks may give rise to novel antiviral drugs that counteract viral-induced disease.

Toxoplasmosis and Polygenic Disease Susceptibility Genes: Extensive Toxoplasma gondii Host/Pathogen Interactome Enrichment in Nine Psychiatric or Neurological Disorders

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C. J. Carter

2013-01-01

Full Text Available Toxoplasma gondii is not only implicated in schizophrenia and related disorders, but also in Alzheimer's or Parkinson's disease, cancer, cardiac myopathies, and autoimmune disorders. During its life cycle, the pathogen interacts with ~3000 host genes or proteins. Susceptibility genes for multiple sclerosis, Alzheimer's disease, schizophrenia, bipolar disorder, depression, childhood obesity, Parkinson's disease, attention deficit hyperactivity disorder (multiple sclerosis, and autism (, but not anorexia or chronic fatigue are highly enriched in the human arm of this interactome and 18 (ADHD to 33% (MS of the susceptibility genes relate to it. The signalling pathways involved in the susceptibility gene/interactome overlaps are relatively specific and relevant to each disease suggesting a means whereby susceptibility genes could orient the attentions of a single pathogen towards disruption of the specific pathways that together contribute (positively or negatively to the endophenotypes of different diseases. Conditional protein knockdown, orchestrated by T. gondii proteins or antibodies binding to those of the host (pathogen derived autoimmunity and metabolite exchange, may contribute to this disruption. Susceptibility genes may thus be related to the causes and influencers of disease, rather than (and as well as to the disease itself.

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...

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.

Dry Eye Disease Incidence Associated with Chronic Graft-Host Disease: Nonconcurrent Cohort Study (An American Ophthalmological Society Thesis)

Science.gov (United States)

Mian, Shahzad I.; De la Parra-Colín, Paola; De Melo-Franco, Rafael; Johnson, Christopher; Barrientos-Gutierrez, Tonatiuh

2015-01-01

Purpose: To determine if chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) is associated with stable or progressive dry eye disease and to determine the true incidence in patients with no prior history of dry eye disease. Methods: A nonconcurrent cohort study at a single institution with 136 patients who had no previous history of dry eye disease before HSCT. Survival analysis was used to estimate dry eye disease incidence. The incidence rate was calculated using life tables as the number of observed dry eye disease cases divided by the person-time at risk accumulated by the cohort. Transition probabilities were calculated from time of transplant to time of diagnosis, and then to last recorded visit. Results: Incidence rate was 0.8 cases of dry eye disease per person-year, and half of the population at risk developed dry eye disease during the first 10 months post transplant. Time to develop dry eye disease was 2.5 months for mild dry eye disease, 9.6 months for moderate dry eye disease, and 13.2 months for severe dry eye disease. In terms of cumulative incidence, 73% of subjects developed dry eye disease (50% mild, 16% moderate, and 7% severe) at the time of diagnosis. Conclusions: Our findings suggest that dry eye disease associated with cGVHD is an extremely frequent event and shows a wide spectrum of severity, with a mild form presenting early and a moderate to severe form presenting later after HSCT. These findings need to be studied further to elucidate if these are two different pathophysiological entities or just different expressions of the same pathology. PMID:27507907

The Role of MicroRNAs in Myeloid Cells during Graft-versus-Host Disease

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Sophia Chen

2018-01-01

Full Text Available The successful treatment of various hematologic diseases with allogeneic hematopoietic cell transplantation is often limited by the occurrence of graft-versus-host disease (GvHD. Several microRNAs (miRs have recently been shown to impact the biology of GvHD by regulating pro- as well as anti-inflammatory target genes. There is increasing evidence that a single miR can have different effects by preferentially targeting certain genes depending on the cell type that the miR is analyzed in. This review will focus on the role of miRs in myeloid cells during the development of acute and chronic GvHD and autoimmune diseases. Because miRs act on the expression of multiple target genes and may thereby influence the immune system at different functional levels, they are potentially attractive targets for the modification of allogeneic immune responses using miR mimics and inhibitors.

Impact of CCR5delta32 Host Genetic Background and Disease Progression on HIV-1 Intrahost Evolutionary Processes: Efficient Hypothesis Testing through Hierarchical Phylogenetic Models

NARCIS (Netherlands)

Edo-Matas, Diana; Lemey, Philippe; Tom, Jennifer A.; Serna-Bolea, Cèlia; van den Blink, Agnes E.; van 't Wout, Angélique B.; Schuitemaker, Hanneke; Suchard, Marc A.

2011-01-01

The interplay between C-C chemokine receptor type 5 (CCR5) host genetic background, disease progression, and intrahost HIV-1 evolutionary dynamics remains unclear because differences in viral evolution between hosts limit the ability to draw conclusions across hosts stratified into clinically

Analysis of protein targets in pathogen-host interaction in infectious diseases: a case study on Plasmodium falciparum and Homo sapiens interaction network.

Science.gov (United States)

Saha, Sovan; Sengupta, Kaustav; Chatterjee, Piyali; Basu, Subhadip; Nasipuri, Mita

2017-09-23

Infection and disease progression is the outcome of protein interactions between pathogen and host. Pathogen, the role player of Infection, is becoming a severe threat to life as because of its adaptability toward drugs and evolutionary dynamism in nature. Identifying protein targets by analyzing protein interactions between host and pathogen is the key point. Proteins with higher degree and possessing some topologically significant graph theoretical measures are found to be drug targets. On the other hand, exceptional nodes may be involved in infection mechanism because of some pathway process and biologically unknown factors. In this article, we attempt to investigate characteristics of host-pathogen protein interactions by presenting a comprehensive review of computational approaches applied on different infectious diseases. As an illustration, we have analyzed a case study on infectious disease malaria, with its causative agent Plasmodium falciparum acting as 'Bait' and host, Homo sapiens/human acting as 'Prey'. In this pathogen-host interaction network based on some interconnectivity and centrality properties, proteins are viewed as central, peripheral, hub and non-hub nodes and their significance on infection process. Besides, it is observed that because of sparseness of the pathogen and host interaction network, there may be some topologically unimportant but biologically significant proteins, which can also act as Bait/Prey. So, functional similarity or gene ontology mapping can help us in this case to identify these proteins. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

[NKT cells and graft-versus-host disease-review].

Science.gov (United States)

Zhao, Lei; Hao, Sha; Yuan, Wei-Ping; Cheng, Tao

2013-10-01

NKT cells (nature killer T cells), as a regulatory cellular compartment in the immune system, express cell surface markers of T cells and NK cells. It secretes a variety of cytokines that stimulate specific antigens. Through regulating the balance of Th1/Th2, the NKT cells play an important role in prevention and treatment of graft-versus-host disease (GVHD). Its antitumor and anti-infectious effects serve as a basis of its application in allogeneic hematopoietic stem cell transplantation. A better understanding of the biological and immunological features of NKT cell, as well as its specific immune regulatory mechanisms, will further justify the rationales of using NKT cells in the management of GVHD for patients. In this review, the biologic properties, classification, differentiation and development, immune activation of NKT cells as well as the NKT cells and GVHD including the related mechanisms of prevention and treatment of GVHD with NKT cells, NKT cells and tumors, NKT cells and infection, and NKT cells and clinical GVHD are summarized.

Targeting hunter distribution based on host resource selection and kill sites to manage disease risk

DEFF Research Database (Denmark)

Dugal, Cherie; van Beest, Floris; Vander Wal, Eric

2013-01-01

Endemic and emerging diseases are rarely uniform in their spatial distribution or prevalence among cohorts of wildlife. Spatial models that quantify risk-driven differences in resource selection and hunter mortality of animals at fine spatial scales can assist disease management by identifying high-risk...... areas and individuals. We used resource selection functions (RSFs) and selection ratios (SRs) to quantify sex- and age-specific resource selection patterns of collared (n = 67) and hunter-killed (n = 796) nonmigratory elk (Cervus canadensis manitobensis) during the hunting season between 2002 and 2012...... juvenile males and hunter-killed adult females. In instances where disease infects a metapopulation and eradication is infeasible, a principle goal of management is to limit the spread of disease among infected animals. We map high-risk areas that are regularly used by potentially infectious hosts...

The role of the ratio of vector and host densities in the evolution of transmission modes in vector-borne diseases. The example of sylvatic Trypanosoma cruzi.

Science.gov (United States)

Pelosse, Perrine; Kribs-Zaleta, Christopher M

2012-11-07

Pathogens may use different routes of transmission to maximize their spread among host populations. Theoretical and empirical work conducted on directly transmitted diseases suggest that horizontal (i.e., through host contacts) and vertical (i.e., from mother to offspring) transmission modes trade off, on the ground that highly virulent pathogens, which produce larger parasite loads, are more efficiently transmitted horizontally, and that less virulent pathogens, which impair host fitness less significantly, are better transmitted vertically. Other factors than virulence such as host density could also select for different transmission modes, but they have barely been studied. In vector-borne diseases, pathogen transmission rate is strongly affected by host-vector relative densities and by processes of saturation in contacts between hosts and vectors. The parasite Trypanosoma cruzi which is transmitted by triatomine bugs to several vertebrate hosts is responsible for Chagas' disease in Latin America. It is also widespread in sylvatic cycles in the southeastern U.S. in which it typically induces no mortality costs to its customary hosts. Besides classical transmission via vector bites, alternative ways to generate infections in hosts such as vertical and oral transmission (via the consumption of vectors by hosts) have been reported in these cycles. The two major T. cruzi strains occurring in the U.S. seem to exhibit differential efficiencies at vertical and classical horizontal transmissions. We investigated whether the vector-host ratio affects the outcome of the competition between the two parasite strains using an epidemiological two-strain model considering all possible transmission routes for sylvatic T. cruzi. We were able to show that the vector-host ratio influences the evolution of transmission modes providing that oral transmission is included in the model as a possible transmission mode, that oral and classical transmissions saturate at different vector-host

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.

Pentraxin 3 plasma levels at graft-versus-host disease onset predict disease severity and response to therapy in children given haematopoietic stem cell transplantation

OpenAIRE

Dander, Erica; De Lorenzo, Paola; Bottazzi, Barbara; Quarello, Paola; Vinci, Paola; Balduzzi, Adriana; Masciocchi, Francesca; Bonanomi, Sonia; Cappuzzello, Claudia; Prunotto, Giulia; Pavan, Fabio; Pasqualini, Fabio; Sironi, Marina; Cuccovillo, Ivan; Leone, Roberto

2016-01-01

Acute Graft-versus-Host Disease (GvHD) remains a major complication of allogeneic haematopoietic stem cell transplantation, with a significant proportion of patients failing to respond to first-line systemic corticosteroids. Reliable biomarkers predicting disease severity and response to treatment are warranted to improve its management. Thus, we sought to determine whether pentraxin 3 (PTX3), an acute-phase protein produced locally at the site of inflammation, could represent a novel acute G...

Host contact and shedding patterns clarify variation in pathogen exposure and transmission in threatened tortoise Gopherus agassizii: implications for disease modelling and management

Science.gov (United States)

Aiello, Christina M.; Nussear, Kenneth E.; Esque, Todd C.; Emblidge, Patrick G.; Sah, Pratha; Bansal, Shweta; Hudson, Peter J.

2016-01-01

Summary Most directly transmitted infections require some form of close contact between infectious and susceptible hosts to spread. Often disease models assume contacts are equal and use mean field estimates of transmission probability for all interactions with infectious hosts.

Host age modulates parasite infectivity, virulence and reproduction.

Science.gov (United States)

Izhar, Rony; Ben-Ami, Frida

2015-07-01

Host age is one of the most striking differences among hosts within most populations, but there is very little data on how age-dependent effects impact ecological and evolutionary dynamics of both the host and the parasite. Here, we examined the influence of host age (juveniles, young and old adults) at parasite exposure on host susceptibility, fecundity and survival as well as parasite transmission, using two clones of the water flea Daphnia magna and two clones of its bacterial parasite Pasteuria ramosa. Younger D. magna were more susceptible to infection than older ones, regardless of host or parasite clone. Also, younger-infected D. magna became castrated faster than older hosts, but host and parasite clone effects contributed to this trait as well. Furthermore, the early-infected D. magna produced considerably more parasite transmission stages than late-infected ones, while host age at exposure did not affect virulence as it is defined in models (host mortality). When virulence is defined more broadly as the negative effects of infection on host fitness, by integrating the parasitic effects on host fecundity and mortality, then host age at exposure seems to slide along a negative relationship between host and parasite fitness. Thus, the virulence-transmission trade-off differs strongly among age classes, which in turn affects predictions of optimal virulence. Age-dependent effects on host susceptibility, virulence and parasite transmission could pose an important challenge for experimental and theoretical studies of infectious disease dynamics and disease ecology. Our results present a call for a more explicit stage-structured theory for disease, which will incorporate age-dependent epidemiological parameters. © 2015 The Authors. Journal of Animal Ecology © 2015 British Ecological Society.

Host Adaptation of Staphylococcal Leukocidins

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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

Timing of host feeding drives rhythms in parasite replication

KAUST Repository

Prior, Kimberley F

2017-12-07

Circadian rhythms enable organisms to synchronise the processes underpinning survival and reproduction to anticipate daily changes in the external environment. Recent work shows that daily (circadian) rhythms also enable parasites to maximise fitness in the context of ecological interactions with their hosts. Because parasite rhythms matter for their fitness, understanding how they are regulated could lead to innovative ways to reduce the severity and spread of diseases. Here, we examine how host circadian rhythms influence rhythms in the asexual replication of malaria parasites. Asexual replication is responsible for the severity of malaria and fuels transmission of the disease, yet, how parasite rhythms are driven remains a mystery. We perturbed feeding rhythms of hosts by 12 hours (i.e. diurnal feeding in nocturnal mice) to desynchronise the host\\'s peripheral oscillators from the central, light-entrained oscillator in the brain and their rhythmic outputs. We demonstrate that the rhythms of rodent malaria parasites in day-fed hosts become inverted relative to the rhythms of parasites in night-fed hosts. Our results reveal that the host\\'s peripheral rhythms (associated with the timing of feeding and metabolism), but not rhythms driven by the central, light-entrained circadian oscillator in the brain, determine the timing (phase) of parasite rhythms. Further investigation reveals that parasite rhythms correlate closely with blood glucose rhythms. In addition, we show that parasite rhythms resynchronise to the altered host feeding rhythms when food availability is shifted, which is not mediated through rhythms in the host immune system. Our observations suggest that parasites actively control their developmental rhythms. Finally, counter to expectation, the severity of disease symptoms expressed by hosts was not affected by desynchronisation of their central and peripheral rhythms. Our study at the intersection of disease ecology and chronobiology opens up a new

Exploring NAD+ metabolism in host-pathogen interactions.

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Mesquita, Inês; Varela, Patrícia; Belinha, Ana; Gaifem, Joana; Laforge, Mireille; Vergnes, Baptiste; Estaquier, Jérôme; Silvestre, Ricardo

2016-03-01

Nicotinamide adenine dinucleotide (NAD(+)) is a vital molecule found in all living cells. NAD(+) intracellular levels are dictated by its synthesis, using the de novo and/or salvage pathway, and through its catabolic use as co-enzyme or co-substrate. The regulation of NAD(+) metabolism has proven to be an adequate drug target for several diseases, including cancer, neurodegenerative or inflammatory diseases. Increasing interest has been given to NAD(+) metabolism during innate and adaptive immune responses suggesting that its modulation could also be relevant during host-pathogen interactions. While the maintenance of NAD(+) homeostatic levels assures an adequate environment for host cell survival and proliferation, fluctuations in NAD(+) or biosynthetic precursors bioavailability have been described during host-pathogen interactions, which will interfere with pathogen persistence or clearance. Here, we review the double-edged sword of NAD(+) metabolism during host-pathogen interactions emphasizing its potential for treatment of infectious diseases.

Nitric oxide production by necrotrophic pathogen Macrophomina phaseolina and the host plant in charcoal rot disease of jute: complexity of the interplay between necrotroph-host plant interactions.

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Tuhin Subhra Sarkar

Full Text Available M. phaseolina, a global devastating necrotrophic fungal pathogen causes charcoal rot disease in more than 500 host plants. With the aim of understanding the plant-necrotrophic pathogen interaction associated with charcoal rot disease of jute, biochemical approach was attempted to study cellular nitric oxide production under diseased condition. This is the first report on M. phaseolina infection in Corchorus capsularis (jute plants which resulted in elevated nitric oxide, reactive nitrogen species and S nitrosothiols production in infected tissues. Time dependent nitric oxide production was also assessed with 4-Amino-5-Methylamino-2',7'-Difluorofluorescein Diacetate using single leaf experiment both in presence of M. phaseolina and xylanases obtained from fungal secretome. Cellular redox status and redox active enzymes were also assessed during plant fungal interaction. Interestingly, M. phaseolina was found to produce nitric oxide which was detected in vitro inside the mycelium and in the surrounding medium. Addition of mammalian nitric oxide synthase inhibitor could block the nitric oxide production in M. phaseolina. Bioinformatics analysis revealed nitric oxide synthase like sequence with conserved amino acid sequences in M. phaseolina genome sequence. In conclusion, the production of nitric oxide and reactive nitrogen species may have important physiological significance in necrotrophic host pathogen interaction.

Syngeneic graft-versus-host disease: a report of two cases and literature review.

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Latif, T; Pohlman, B; Kalaycio, M; Sobecks, R; Hsi, E D; Andresen, S; Bolwell, B J

2003-09-01

Rappeport et al first reported the clinical syndrome of graft-versus-host disease (GVHD) in syngeneic bone marrow transplant patients. Recently, there have been more reports of a GVHD-like syndrome in syngeneic bone marrow transplant patients (SGVHD) that may result in significant clinical morbidity. A total of 17 cases of SGVHD in syngeneic bone marrow transplant patients have been reported to date in the medical literature. The current report reviews these cases and presents two additional cases of severe SGVHD that have occurred at our institution.

Transcriptional portrait of Actinobacillus pleuropneumoniae during acute disease--potential strategies for survival and persistence in the host.

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Kirstine Klitgaard

Full Text Available BACKGROUND: Gene expression profiles of bacteria in their natural hosts can provide novel insight into the host-pathogen interactions and molecular determinants of bacterial infections. In the present study, the transcriptional profile of the porcine lung pathogen Actinobacillus pleuropneumoniae was monitored during the acute phase of infection in its natural host. METHODOLOGY/PRINCIPAL FINDINGS: Bacterial expression profiles of A. pleuropneumoniae isolated from lung lesions of 25 infected pigs were compared in samples taken 6, 12, 24 and 48 hours post experimental challenge. Within 6 hours, focal, fibrino hemorrhagic lesions could be observed in the pig lungs, indicating that A. pleuropneumoniae had managed to establish itself successfully in the host. We identified 237 differentially regulated genes likely to encode functions required by the bacteria for colonization and survival in the host. This group was dominated by genes involved in various aspects of energy metabolism, especially anaerobic respiration and carbohydrate metabolism. Remodeling of the bacterial envelope and modifications of posttranslational processing of proteins also appeared to be of importance during early infection. The results suggested that A. pleuropneumoniae is using various strategies to increase its fitness, such as applying Na+ pumps as an alternative way of gaining energy. Furthermore, the transcriptional data provided potential clues as to how A. pleuropneumoniae is able to circumvent host immune factors and survive within the hostile environment of host macrophages. This persistence within macrophages may be related to urease activity, mobilization of various stress responses and active evasion of the host defenses by cell surface sialylation. CONCLUSIONS/SIGNIFICANCE: The data presented here highlight the importance of metabolic adjustments to host conditions as virulence factors of infecting microorganisms and help to provide insight into the mechanisms

Host genetic risk factors for West Nile virus infection and disease progression.

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Abigail W Bigham

Full Text Available West Nile virus (WNV, a category B pathogen endemic in parts of Africa, Asia and Europe, emerged in North America in 1999, and spread rapidly across the continental U.S. Outcomes of infection with WNV range from asymptomatic to severe neuroinvasive disease manifested as encephalitis, paralysis, and/or death. Neuroinvasive WNV disease occurs in less than one percent of cases, and although host genetic factors are thought to influence risk for symptomatic disease, the identity of these factors remains largely unknown. We tested 360 common haplotype tagging and/or functional SNPs in 86 genes that encode key regulators of immune function in 753 individuals infected with WNV including: 422 symptomatic WNV cases and 331 cases with asymptomatic infections. After applying a Bonferroni correction for multiple tests and controlling for population stratification, SNPs in IRF3 (OR 0.54, p = 0.035 and MX1, (OR 0.19, p = 0.014 were associated with symptomatic WNV infection and a single SNP in OAS1 (OR 9.79, p = 0.003 was associated with increased risk for West Nile encephalitis and paralysis (WNE/P. Together, these results suggest that genetic variation in the interferon response pathway is associated with both risk for symptomatic WNV infection and WNV disease progression.

The interaction of host genetics and disease processes in chronic livestock disease: a simulation model of ovine footrot.

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Russell, V N L; Green, L E; Bishop, S C; Medley, G F

2013-03-01

A stochastic, individual-based, simulation model of footrot in a flock of 200 ewes was developed that included flock demography, disease processes, host genetic variation for traits influencing infection and disease processes, and bacterial contamination of the environment. Sensitivity analyses were performed using ANOVA to examine the contribution of unknown parameters to outcome variation. The infection rate and bacterial death rate were the most significant factors determining the observed prevalence of footrot, as well as the heritability of resistance. The dominance of infection parameters in determining outcomes implies that observational data cannot be used to accurately estimate the strength of genetic control of underlying traits describing the infection process, i.e. resistance. Further work will allow us to address the potential for genetic selection to control ovine footrot. Copyright © 2012 Elsevier B.V. All rights reserved.

Nestedness of ectoparasite-vertebrate host networks.

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Sean P Graham

2009-11-01

Full Text Available Determining the structure of ectoparasite-host networks will enable disease ecologists to better understand and predict the spread of vector-borne diseases. If these networks have consistent properties, then studying the structure of well-understood networks could lead to extrapolation of these properties to others, including those that support emerging pathogens. Borrowing a quantitative measure of network structure from studies of mutualistic relationships between plants and their pollinators, we analyzed 29 ectoparasite-vertebrate host networks--including three derived from molecular bloodmeal analysis of mosquito feeding patterns--using measures of nestedness to identify non-random interactions among species. We found significant nestedness in ectoparasite-vertebrate host lists for habitats ranging from tropical rainforests to polar environments. These networks showed non-random patterns of nesting, and did not differ significantly from published estimates of nestedness from mutualistic networks. Mutualistic and antagonistic networks appear to be organized similarly, with generalized ectoparasites interacting with hosts that attract many ectoparasites and more specialized ectoparasites usually interacting with these same "generalized" hosts. This finding has implications for understanding the network dynamics of vector-born pathogens. We suggest that nestedness (rather than random ectoparasite-host associations can allow rapid transfer of pathogens throughout a network, and expand upon such concepts as the dilution effect, bridge vectors, and host switching in the context of nested ectoparasite-vertebrate host networks.

CXCR1 regulates pulmonary anti-Pseudomonas host defense

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Carevic, M.; Öz, H.; Fuchs, K.; Laval, J.; Schroth, C.; Frey, N.; Hector, A.; Bilich, T.; Haug, M.; Schmidt, A.; Autenrieth, S. E.; Bucher, K.; Beer-Hammer, S.; Gaggar, A.; Kneilling, M.; Benarafa, C.; Gao, J.; Murphy, P.; Schwarz, S.; Moepps, B.; Hartl, D.

2016-01-01

Pseudomonas aeruginosa is a key opportunistic pathogen causing disease in cystic fibrosis (CF) and other lung diseases such as chronic obstructive pulmonary disease (COPD). However, the pulmonary host defense mechanisms regulating anti-Pseudomonas aeruginosa immunity remain incompletely understood. Here we demonstrate, by studying an airway Pseudomonas aeruginosa infection model, in vivo bioluminescence imaging, neutrophil effector responses and human airway samples, that the chemokine receptor CXCR1 regulates pulmonary host defense against Pseudomonas aeruginosa. Mechanistically, CXCR1 regulated anti-Pseudomonas neutrophil responses through modulation of reactive oxygen species and interference with toll-like receptor 5 expression. These studies define CXCR1 as a novel non-canonical chemokine receptor that regulates pulmonary anti-Pseudomonas host defense with broad implications for CF, COPD and other infectious lung diseases. PMID:26950764

Quality of life of patients with graft-versus-host disease (GvHD post-hematopoietic stem cell transplantation

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Sibéli de Fátima Ferraz Simão Proença

Full Text Available Abstract OBJECTIVE Assessing the quality of life of adult patients with hematological cancer in the 100 days after transplantation of hematopoietic stem cells and verifying whether the variable graft-versus-host disease (GvHD is predictive of worse results. METHOD An observational correlational and quantitative study with 36 adult participants diagnosed with hematologic cancer who underwent hematopoietic stem cell transplantation from September 2013 to June 2015. RESULT The mean age was 37 years, 52.78% were female, and 61.11% were diagnosed with leukemia. Quality of life scores showed a significant impact between pre-transplantation and pre-hospital discharge, and also within the 100 days post-transplantation. The statistical analysis between the scores for the groups with and without GvHD showed a significant difference between the presence of the complication and worse results. CONCLUSION Quality of life is altered as a result of hematopoietic stem cells transplantation, especially in patients who have graft-versus-host disease.

Mesenchymal Stromal Cells: What Is the Mechanism in Acute Graft-Versus-Host Disease?

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Neil Dunavin

2017-07-01

Full Text Available After more than a decade of preclinical and clinical development, therapeutic infusion of mesenchymal stromal cells is now a leading investigational strategy for the treatment of acute graft-versus-host disease (GVHD. While their clinical use continues to expand, it is still unknown which of their immunomodulatory properties contributes most to their therapeutic activity. Herein we describe the proposed mechanisms, focusing on the inhibitory activity of mesenchymal stromal cells (MSCs at immunologic checkpoints. A deeper understanding of the mechanism of action will allow us to design more effective treatment strategies.

The Drosophila melanogaster host model

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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

The Drosophila melanogaster host model

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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.

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.

Viroids: how to infect a host and cause disease without encoding proteins.

Science.gov (United States)

Navarro, Beatriz; Gisel, Andreas; Rodio, Maria-Elena; Delgado, Sonia; Flores, Ricardo; Di Serio, Francesco

2012-07-01

Despite being composed by a single-stranded, circular, non-protein-coding RNA of just 246-401 nucleotides (nt), viroids can incite in their host plants symptoms similar to those caused by DNA and RNA viruses, which have genomes at least 20-fold bigger and encode proteins. On the other hand, certain non-protein-coding plant satellite RNAs display structural similarities with viroids but for replication and transmission they need to parasitize specific helper viruses (modifying concomitantly the symptoms they induce). While phenotypic alterations accompanying infection by viruses may partly result from expressing the proteins they code for, how the non-protein-coding viroids (and satellite RNAs) cause disease remains a conundrum. Initial ideas on viroid pathogenesis focused on a direct interaction of the genomic RNA with host proteins resulting in their malfunction. With the advent of RNA silencing, it was alternatively proposed that symptoms could be produced by viroid-derived small RNAs (vd-sRNAs) -generated by the host defensive machinery- targeting specific host mRNA or DNA sequences for post-transcriptional or transcriptional gene silencing, respectively, a hypothesis that could also explain pathogenesis of non-protein-coding satellite RNAs. Evidence sustaining this view has been circumstantial, but recent data provide support for it in two cases: i) the yellow symptoms associated with a specific satellite RNA result from a 22-nt small RNA (derived from the 24-nt fragment of the satellite genome harboring the pathogenic determinant), which is complementary to a segment of the mRNA of the chlorophyll biosynthetic gene CHLI and targets it for cleavage by the RNA silencing machinery, and ii) two 21-nt vd-sRNAS containing the pathogenic determinant of the albino phenotype induced by a chloroplast-replicating viroid target for cleavage the mRNA coding for the chloroplastic heat-shock protein 90 via RNA silencing too. This evidence, which is compelling for the

Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease

Science.gov (United States)

Jostins, Luke; Ripke, Stephan; Weersma, Rinse K; Duerr, Richard H; McGovern, Dermot P; Hui, Ken Y; Lee, James C; Schumm, L Philip; Sharma, Yashoda; Anderson, Carl A; Essers, Jonah; Mitrovic, Mitja; Ning, Kaida; Cleynen, Isabelle; Theatre, Emilie; Spain, Sarah L; Raychaudhuri, Soumya; Goyette, Philippe; Wei, Zhi; Abraham, Clara; Achkar, Jean-Paul; Ahmad, Tariq; Amininejad, Leila; Ananthakrishnan, Ashwin N; Andersen, Vibeke; Andrews, Jane M; Baidoo, Leonard; Balschun, Tobias; Bampton, Peter A; Bitton, Alain; Boucher, Gabrielle; Brand, Stephan; Büning, Carsten; Cohain, Ariella; Cichon, Sven; D’Amato, Mauro; De Jong, Dirk; Devaney, Kathy L; Dubinsky, Marla; Edwards, Cathryn; Ellinghaus, David; Ferguson, Lynnette R; Franchimont, Denis; Fransen, Karin; Gearry, Richard; Georges, Michel; Gieger, Christian; Glas, Jürgen; Haritunians, Talin; Hart, Ailsa; Hawkey, Chris; Hedl, Matija; Hu, Xinli; Karlsen, Tom H; Kupcinskas, Limas; Kugathasan, Subra; Latiano, Anna; Laukens, Debby; Lawrance, Ian C; Lees, Charlie W; Louis, Edouard; Mahy, Gillian; Mansfield, John; Morgan, Angharad R; Mowat, Craig; Newman, William; Palmieri, Orazio; Ponsioen, Cyriel Y; Potocnik, Uros; Prescott, Natalie J; Regueiro, Miguel; Rotter, Jerome I; Russell, Richard K; Sanderson, Jeremy D; Sans, Miquel; Satsangi, Jack; Schreiber, Stefan; Simms, Lisa A; Sventoraityte, Jurgita; Targan, Stephan R; Taylor, Kent D; Tremelling, Mark; Verspaget, Hein W; De Vos, Martine; Wijmenga, Cisca; Wilson, David C; Winkelmann, Juliane; Xavier, Ramnik J; Zeissig, Sebastian; Zhang, Bin; Zhang, Clarence K; Zhao, Hongyu; Silverberg, Mark S; Annese, Vito; Hakonarson, Hakon; Brant, Steven R; Radford-Smith, Graham; Mathew, Christopher G; Rioux, John D; Schadt, Eric E; Daly, Mark J; Franke, Andre; Parkes, Miles; Vermeire, Severine; Barrett, Jeffrey C; Cho, Judy H

2012-01-01

Crohn’s disease (CD) and ulcerative colitis (UC), the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry with rising prevalence in other populations1. Genome-wide association studies (GWAS) and subsequent meta-analyses of CD and UC2,3 as separate phenotypes implicated previously unsuspected mechanisms, such as autophagy4, in pathogenesis and showed that some IBD loci are shared with other inflammatory diseases5. Here we expand knowledge of relevant pathways by undertaking a meta-analysis of CD and UC genome-wide association scans, with validation of significant findings in more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional and balancing selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe striking overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD. PMID:23128233

Targeting hunter distribution based on host resource selection and kill sites to manage disease risk.

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Dugal, Cherie J; van Beest, Floris M; Vander Wal, Eric; Brook, Ryan K

2013-10-01

Endemic and emerging diseases are rarely uniform in their spatial distribution or prevalence among cohorts of wildlife. Spatial models that quantify risk-driven differences in resource selection and hunter mortality of animals at fine spatial scales can assist disease management by identifying high-risk areas and individuals. We used resource selection functions (RSFs) and selection ratios (SRs) to quantify sex- and age-specific resource selection patterns of collared (n = 67) and hunter-killed (n = 796) nonmigratory elk (Cervus canadensis manitobensis) during the hunting season between 2002 and 2012, in southwestern Manitoba, Canada. Distance to protected area was the most important covariate influencing resource selection and hunter-kill sites of elk (AICw = 1.00). Collared adult males (which are most likely to be infected with bovine tuberculosis (Mycobacterium bovis) and chronic wasting disease) rarely selected for sites outside of parks during the hunting season in contrast to adult females and juvenile males. The RSFs showed selection by adult females and juvenile males to be negatively associated with landscape-level forest cover, high road density, and water cover, whereas hunter-kill sites of these cohorts were positively associated with landscape-level forest cover and increasing distance to streams and negatively associated with high road density. Local-level forest was positively associated with collared animal locations and hunter-kill sites; however, selection was stronger for collared juvenile males and hunter-killed adult females. In instances where disease infects a metapopulation and eradication is infeasible, a principle goal of management is to limit the spread of disease among infected animals. We map high-risk areas that are regularly used by potentially infectious hosts but currently underrepresented in the distribution of kill sites. We present a novel application of widely available data to target hunter distribution based on host resource

Pulp Obliteration in a Patient with Sclerodermatous Chronic Graft-versus-Host Disease.

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Gomes, Camilla Borges Ferreira; Treister, Nathaniel Simon; Miller, Brian; Armand, Philippe; Friedland, Bernard

2016-04-01

Dental pulp calcification is a common finding associated with localized dental trauma, genetic disorders, and systemic inflammatory diseases. Chronic graft-versus-host disease (cGVHD) is a frequent complication after allogeneic hematopoietic cell transplantation (allo-HCT) characterized by immune-mediated injury to the skin, mouth, eyes, liver, and other tissues, resulting in significant disability and reduced quality of life. We report a patient with sclerodermatous cGVHD who presented with general pulp calcification in all teeth 5 years after allo-HCT. A review of full mouth dental radiographs obtained just before allo-HCT revealed normal-appearing pulp chambers. Based on prior reports of generalized pulp calcification associated with progressive systemic sclerosis, we hypothesized that the etiology was likely related to the presence of cGVHD with associated vascular and fibrotic tissue changes within the pulp vasculature. Clinicians should consider cGVHD in the differential diagnosis of generalized pulp calcification. Copyright © 2016 American Association of Endodontists. All rights reserved.

Host and Potential Vector Susceptibility to an Emerging Orbivirus in the United States: Epizootic Hemorrhagic Disease Virus Serotype 6.

Science.gov (United States)

Ruder, M G; Stallknecht, D E; Allison, A B; Mead, D G; Carter, D L; Howerth, E W

2016-05-01

Epizootic hemorrhagic disease viruses (EHDVs) are orbiviruses transmitted by Culicoides biting midges to domestic and wild ruminants. EHDV-1 and EHDV-2 are endemic in the United States, where epizootic hemorrhagic disease is the most significant viral disease of white-tailed deer (WTD;Odocoileus virginianus) and reports of epizootic hemorrhagic disease in cattle are increasing. In 2006, a reassortant EHDV-6 was isolated from dead WTD in Indiana and has been detected each subsequent year over a wide geographic region. Since EHDV-6 is not a historically endemic serotype in the United States, it is important to understand infection outcome in potential hosts. Specifically, we aimed to evaluate the pathogenicity of the virus in 2 primary US ruminant hosts (WTD and cattle) and the susceptibility of a confirmed US vector (Culicoides sonorensis). Five WTD and 4 cattle were inoculated with >10(6)TCID50EHDV-6 by intradermal and subcutaneous injection. All 5 WTD exhibited moderate to severe disease, and 3 died. Viremia was first detected 3 to 5 days postinfection (dpi) with surviving animals seroconverting by 10 dpi. Two of 4 inoculated cattle had detectable viremia, 5 to 10 dpi and 7 to 24 dpi, respectively. No clinical, hematologic, or pathologic abnormalities were observed. Antibodies were detected by 10 dpi in 3 of 4 cows.C. sonorensis were fed on WTD blood spiked with EHDV-6 and held for 4 to 14 days postfeeding at 25°C. From 4 to 14 days postfeeding, 19 of 171 midges were virus isolation positive and 6 of 171 had ≥10(2.7)TCID50EHDV-6. Although outcomes varied, these studies demonstrate the susceptibility of ruminant and vector hosts in the United States for this recently emerged EHDV serotype. © The Author(s) 2015.

The role of host genetic factors in respiratory tract infectious diseases: systematic review, meta-analyses and field synopsis

NARCIS (Netherlands)

Patarčić, Inga; Gelemanović, Andrea; Kirin, Mirna; Kolčić, Ivana; Theodoratou, Evropi; Baillie, Kenneth J.; de Jong, Menno D.; Rudan, Igor; Campbell, Harry; Polašek, Ozren

2015-01-01

Host genetic factors have frequently been implicated in respiratory infectious diseases, often with inconsistent results in replication studies. We identified 386 studies from the total of 24,823 studies identified in a systematic search of four bibliographic databases. We performed meta-analyses of

Tipping the balance: Sclerotinia sclerotiorum secreted oxalic acid suppresses host defenses by manipulating the host redox environment.

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Brett Williams

2011-06-01

Full Text Available Sclerotinia sclerotiorum is a necrotrophic ascomycete fungus with an extremely broad host range. This pathogen produces the non-specific phytotoxin and key pathogenicity factor, oxalic acid (OA. Our recent work indicated that this fungus and more specifically OA, can induce apoptotic-like programmed cell death (PCD in plant hosts, this induction of PCD and disease requires generation of reactive oxygen species (ROS in the host, a process triggered by fungal secreted OA. Conversely, during the initial stages of infection, OA also dampens the plant oxidative burst, an early host response generally associated with plant defense. This scenario presents a challenge regarding the mechanistic details of OA function; as OA both suppresses and induces host ROS during the compatible interaction. In the present study we generated transgenic plants expressing a redox-regulated GFP reporter. Results show that initially, Sclerotinia (via OA generates a reducing environment in host cells that suppress host defense responses including the oxidative burst and callose deposition, akin to compatible biotrophic pathogens. Once infection is established however, this necrotroph induces the generation of plant ROS leading to PCD of host tissue, the result of which is of direct benefit to the pathogen. In contrast, a non-pathogenic OA-deficient mutant failed to alter host redox status. The mutant produced hypersensitive response-like features following host inoculation, including ROS induction, callose formation, restricted growth and cell death. These results indicate active recognition of the mutant and further point to suppression of defenses by the wild type necrotrophic fungus. Chemical reduction of host cells with dithiothreitol (DTT or potassium oxalate (KOA restored the ability of this mutant to cause disease. Thus, Sclerotinia uses a novel strategy involving regulation of host redox status to establish infection. These results address a long-standing issue

Characterization of early host responses in adults with dengue disease

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Ling Ling

2011-08-01

Full Text Available Abstract Background While dengue-elicited early and transient host responses preceding defervescence could shape the disease outcome and reveal mechanisms of the disease pathogenesis, assessment of these responses are difficult as patients rarely seek healthcare during the first days of benign fever and thus data are lacking. Methods In this study, focusing on early recruitment, we performed whole-blood transcriptional profiling on denguevirus PCR positive patients sampled within 72 h of self-reported fever presentation (average 43 h, SD 18.6 h and compared the signatures with autologous samples drawn at defervescence and convalescence and to control patients with fever of other etiology. Results In the early dengue fever phase, a strong activation of the innate immune response related genes were seen that was absent at defervescence (4-7 days after fever debut, while at this second sampling genes related to biosynthesis and metabolism dominated. Transcripts relating to the adaptive immune response were over-expressed in the second sampling point with sustained activation at the third sampling. On an individual gene level, significant enrichment of transcripts early in dengue disease were chemokines CCL2 (MCP-1, CCL8 (MCP-2, CXCL10 (IP-10 and CCL3 (MIP-1α, antimicrobial peptide β-defensin 1 (DEFB1, desmosome/intermediate junction component plakoglobin (JUP and a microRNA which may negatively regulate pro-inflammatory cytokines in dengue infected peripheral blood cells, mIR-147 (NMES1. Conclusions These data show that the early response in patients mimics those previously described in vitro, where early assessment of transcriptional responses has been easily obtained. Several of the early transcripts identified may be affected by or mediate the pathogenesis and deserve further assessment at this timepoint in correlation to severe disease.

Allogeneic peripheral blood stem cell transplantation in patients with haematological malignancies

International Nuclear Information System (INIS)

Shamsi, T.S.; Irfan, M.; Ansari, S.H.; Farzana, T.; Kahlid, M.Z.; Panwani, V.K.; Baig, M.I.; Shakoor, N.

2004-01-01

Objective: To report the initial data on allogeneic peripheral blood stem cell transplantation for haematogical malignancies in Pakistan. Patients and Methods: Patients with haematological malignancies were included who had received allogeneic PBSC transplantation of Filgrastim (rhG-CSF) mobilized peripheral blood stem cells from HLA-identical siblings (except one 5/6 antigen sibling) with Busulphan and Cyclophosphamide standard conditioning therapy in all patients. No patient received antibiotics for gut decontamination. Empirical antibiotics included Ceftriaxone and Amikacin for febrile neutropenia, oral Itraconazole for antifungal prophylaxis while oral acyclovir was used for antiviral prophylaxis. All donors and recipients were CMV IgG positive Cyclosporin A / Methotrexate were given for graft versus host disease (GvHD) prophylaxis. Stem cells were harvested using Haemonetics MCS+ cell separator. All patients received G-CSF starting from day +4 until their neutrophil count rose to normal. Results: There were 21 patients with age range of 8-38 years and male to female ratio of 2:1. Engraftment was achieved in all patients; median time to absolute neutrophil count of > 0.5 x 10/sup 9/I was 10 days (range 8 -12 days) and platelet count of > 20 x 10/sup 9/1 was 14 days (12-17 days). Acute graft versus host disease (aGvHD) was seen in 7 patients; one patient had grade IV skin and hepatic GvHD; another patient had grade III gut GvHD, grade II GvHD was seen in 3 patients while grade I skin aGvHD was seen in 2 patients. Median hospital stay was 34 days. Treatment related mortality was seen in 3 patients (18%). Chronic GvHD was seen in 5 patients. Four more patients died during the follow-up period. Malaria was seen in 2 while tuberculosis developed in one case. Relapse was seen in 2 patients. The estimated probability of survival at one hundred day, at one year and five years was 82, 47 and 40 percent respectively. Conclusion: Haematopoietic stem cell transplant

Host specialization in ticks and transmission of tick-borne diseases: a review.

Science.gov (United States)

McCoy, Karen D; Léger, Elsa; Dietrich, Muriel

2013-01-01

Determining patterns of host use, and the frequency at which these patterns change, are of key importance if we are to understand tick population dynamics, the evolution of tick biodiversity, and the circulation and evolution of associated pathogens. The question of whether ticks are typically host specialists or host generalists has been subject to much debate over the last half-century. Indeed, early research proposed that morphological diversity in ticks was linked to host specific adaptations and that most ticks were specialists. Later work disputed this idea and suggested that ticks are largely limited by biogeographic conditions and tend to use all locally available host species. The work presented in this review suggests that the actual answer likely lies somewhere between these two extremes. Although recent observational studies support the view that phylogenetically diverse host species share ticks when found on similar ecological ranges, theory on host range evolution predicts that host specialization should evolve in ticks given their life history characteristics. Contemporary work employing population genetic tools to examine host-associated population structure in several tick systems support this prediction and show that simple species records are not enough to determine whether a parasite is a true host generalist; host specialization does evolve in ticks at local scales, but may not always lead to speciation. Ticks therefore seem to follow a pattern of being global generalists, local specialists. Given this, the notion of host range needs to be modified from an evolutionary perspective, where one simply counts the number of hosts used across the geographic distribution, to a more ecological view, where one considers host use at a local scale, if we are to better understand the circulation of tick-borne pathogens and exposure risks for humans and livestock.

Estimating host genetic effects on susceptibility and infectivity to infectious diseases and their contribution to response to selection

NARCIS (Netherlands)

Anche, M.T.

2016-01-01

Mahlet Teka Anche. (2016). Estimating host genetic effects on susceptibility and infectivity to infectious diseases and their contribution to response to selection. PhD thesis, Wageningen University, the Netherlands

Genetic approaches aiming to reduce the prevalence of an infection in a

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.

Economic evaluation of posaconazole versus fluconazole prophylaxis in patients with graft-versus-host disease (GVHD) in the Netherlands

NARCIS (Netherlands)

J.P. Jansen (Jeroen); A.K. O'Sullivan (Amy); P.J. Lugtenburg (Pieternella); L.F.R. Span (Lambert); J.J.W.M. Janssen (Jeroen); W.B. Stam (Wiro)

2010-01-01

textabstractThe objective of this study was to evaluate the cost-effectiveness of posaconazole versus fluconazole for the prevention of invasive fungal infections (IFI) in graft-versus-host disease (GVHD) patients in the Netherlands. A decision analytic model was developed based on a double-blind

An update on the clinical utility of extracorporeal photopheresis in the treatment of graft-versus-host disease

Directory of Open Access Journals (Sweden)

Salem B

2017-03-01

Full Text Available Baheyeldin Salem,1,2 Jennifer Webb,3 David Alex Jacobsohn1,2 1Blood and Marrow Transplant Program, 2Department of Paediatrics, 3Department of Transfusion Medicine, Children’s National Health System, Washington, DC, USA Abstract: Graft-versus-host disease (GVHD continues to be a major complication following allogeneic hematopoietic cell transplantation (allo-HCT with high morbidity and mortality. Corticosteroids are the first-line treatment for GVHD; however, a substantial number of patients go on to require second-line treatment where no single therapeutic modality has been proven to be the most effective. Extracorporeal photopheresis (ECP is an efficient and established therapy for cutaneous T-cell lymphoma, GVHD, rejection after solid organ transplantation and various autoimmune diseases. Although large randomized trials are limited, there is compelling cumulative data on the efficacy of ECP for GVHD, and the response rates, especially for cutaneous involvement, are encouraging. ECP has an excellent safety profile, a well-documented steroid-sparing effect, proven survival benefit and overall quality-of-life improvement. In many institutions, ECP is commonly regarded as the preferred second-line treatment for GVHD. Keywords: GVHD, ECP, immunosuppressive therapy, IST, apheresis, steroid-refractory ­graft-versus-host disease, hematopoietic cell transplantation, graft versus leukemia effect

Host and pathogen ecology drive the seasonal dynamics of a fungal disease, white-nose syndrome.

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Langwig, Kate E; Frick, Winifred F; Reynolds, Rick; Parise, Katy L; Drees, Kevin P; Hoyt, Joseph R; Cheng, Tina L; Kunz, Thomas H; Foster, Jeffrey T; Kilpatrick, A Marm

2015-01-22

Seasonal patterns in pathogen transmission can influence the impact of disease on populations and the speed of spatial spread. Increases in host contact rates or births drive seasonal epidemics in some systems, but other factors may occasionally override these influences. White-nose syndrome, caused by the emerging fungal pathogen Pseudogymnoascus destructans, is spreading across North America and threatens several bat species with extinction. We examined patterns and drivers of seasonal transmission of P. destructans by measuring infection prevalence and pathogen loads in six bat species at 30 sites across the eastern United States. Bats became transiently infected in autumn, and transmission spiked in early winter when bats began hibernating. Nearly all bats in six species became infected by late winter when infection intensity peaked. In summer, despite high contact rates and a birth pulse, most bats cleared infections and prevalence dropped to zero. These data suggest the dominant driver of seasonal transmission dynamics was a change in host physiology, specifically hibernation. Our study is the first, to the best of our knowledge, to describe the seasonality of transmission in this emerging wildlife disease. The timing of infection and fungal growth resulted in maximal population impacts, but only moderate rates of spatial spread. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Efficacy and Safety of Topical Corticosteroids for Management of Oral Chronic Graft versus Host Disease

OpenAIRE

Elsaadany, Basma Abdelaleem; Ahmed, Eman Magdy; Aghbary, Sana Maher Hasan

2017-01-01

Background. Oral chronic graft versus host disease (cGVHD) is a major complication in transplantation community, a problem that can be addressed with topical intervention. Topical corticosteroids are the first line of treatment although the choice remains challenging as none of the available treatments is supported by strong clinical evidence. Objective. This systematic review aims to determine the clinical efficacy and safety of topical corticosteroids for the management of the mucosal alter...

Idelalisib-induced colitis and skin eruption mimicking graft-versus-host disease.

Science.gov (United States)

Hammami, Muhammad Bader; Al-Taee, Ahmad; Meeks, Marshall; Fesler, Mark; Hurley, M Yadira; Cao, Dengfeng; Lai, Jin-Ping

2017-04-01

Idelalisib is a selective inhibitor of the delta isoform of phosphatidylinositol 3-kinase which was approved by the United States Federal Drug Administration in 2014 for the treatment of relapsed chronic lymphocytic leukemia and indolent non-Hodgkin lymphoma. Drug-induced injury of the gastrointestinal tract is a relatively frequent but usually under-recognized disease entity. We report the case of a 56-year-old male with a history of relapsed follicular lymphoma status post allogenic bone marrow transplant who developed severe diarrhea with a skin eruption mimicking graft-versus-host disease (GVHD) 6 months after starting idelalisib. He underwent a colonoscopy demonstrating a grossly normal-appearing colon and terminal ileum. Biopsies taken during the procedure revealed mild active ileitis, colitis, and proctitis with frequent epithelial apoptosis, and focal intra-epithelial lymphocytosis. Skin biopsies revealed sub-acute spongiotic dermatitis suggestive of either contact dermatitis or an eczematous drug reaction. Symptoms were attributed to idelalisib given their resolution with withdrawal of the drug in conjunction with the skin and colonic biopsies. High clinical suspicion and awareness of the histological features of idelalisib-associated colitis is important to distinguish it from potential mimickers such as GVHD and infectious colitis.

Sclerodermatous GVHD after Allogeneic Bone Marrow Transplant: a Review

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Gagan Raju

2017-05-01

Full Text Available Chronic graft versus host disease (cGVHD is the leading cause of non-relapse mortality after allogeneic hematopoietic bone marrow transplantation (HCT for blood malignancy in patients who survive for more than two years. cGVHD can significantly affect quality of life and cause decreased mobility amongst other grave consequences such as end-organ damage, contributing to morbidity and mortality rates for recipients of HCT. Unlike acute GVHD (aGVHD, the chronic variant of graft versus host disease (GVHD has complex immunopathology involving both humoral and cell immunity. It typically affects the integumentary system, though is known to also affect myofascial, mucocutaneous tissues as well as cause end organ damage ultimately resulting in death. Sclerodermatous cGVHD is a type of cGVHD characterized by involvement of the skin, subcutaneous tissue and fascia without evidence of disease in the viscera. Manifestations of this disease are often evocative of autoimmune disease, which is a self-directed inflammatory reaction to the innate and adaptive immune system in various tissues or multiple organ systems. This inflammatory reaction gives rise to autoantibodies as well as B-cell and T-cell mediated direct toxicity which can cause chronic inflammatory changes of tissues ultimately resulting in tissue scarring and end organ dysfunction. We aim to review the literature on this grave disease and elucidate aspects of the immunopathology of chronic sclerodermatous GVHD in hopes that it may lead to revelations inspiring novel therapies after its diagnosis or preventative measures before stem cell transplantation for malignancy.

Steroid treatment of acute graft-versus-host disease grade I: a randomized trial

OpenAIRE

Bacigalupo, Andrea; Milone, Giuseppe; Cupri, Alessandra; Severino, Antonio; Fagioli, Franca; Berger, Massimo; Santarone, Stella; Chiusolo, Patrizia; Sica, Simona; Mammoliti, Sonia; Sorasio, Roberto; Massi, Daniela; Van Lint, Maria Teresa; Raiola, Anna Maria; Gualandi, Francesca

2017-01-01

Patients with acute graft-versus-host disease (GvHD) grade I were randomized to an observation arm (n=85) or to a treatment arm (n=86) consisting of 6-methylprednisolone 1 mg/kg/day, after stratification for age and donor type. The primary end point was development of grade II–IV GvHD. The cumulative incidence of grade II–IV GvHD was 50% in the observation arm and 33% in the treatment arm (P=0.005). However, grade III–IV GvHD was comparable (13% vs. 10%, respectively; P=0.6), and this was tru...

Ocular manifestations of graft-versus-host disease

Science.gov (United States)

Nassar, Amr; Tabbara, Khalid F.; Aljurf, Mahmoud

2013-01-01

Allogeneic hematopoietic stem cell transplantation (HSCT) has evolved over the past two decades to become the standard of care for hematologic and lymphoid malignancies. Major ocular complications after allogeneic HSCT have been increasing in number and severity. Graft-versus-host disease (GVHD) remains a major cause of ocular morbidity after allogeneic HSCT. The main objective of this review is to elucidate the ocular complications in patients developing GVHD following HSCT. Ocular complications secondary to GVHD are common and include dry eye syndrome, acquisition of ocular allergy from donors with allergic disorders. Eyelid changes may occur in GVHD leading to scleroderma-like changes. Patients may develop poliosis, madarosis, vitiligo, lagophthalmos, and entropion. The cornea may show filamentary keratitis, superficial punctate keratitis, corneal ulcers, and peripheral corneal melting which may lead to perforation in severe cases. Scleritis may also occur which can be anterior or posterior. Keratoconjunctivis sicca appears to be the most common presentation of GVHD. The lacrimal glands may be involved with mononuclear cell infiltration of both the major and accessory lacrimal glands and decrease in tear production. Severe dry eye syndrome in patients with GVHD may develop conjunctival scarring, keratinization, and cicatrization of the conjunctiva. Therapy of GVHD includes systemic immunosuppression and local therapy. Surgical treatment in refractory cases includes surgical intervention to improve the manifestation of GVHD of the eye. This may include tarsorrhapy, prose lenses, punctal occlusions and corneal transplantation. PMID:24227989

Timing of host feeding drives rhythms in parasite replication

KAUST Repository

Prior, Kimberley F.

2018-02-26

Circadian rhythms enable organisms to synchronise the processes underpinning survival and reproduction to anticipate daily changes in the external environment. Recent work shows that daily (circadian) rhythms also enable parasites to maximise fitness in the context of ecological interactions with their hosts. Because parasite rhythms matter for their fitness, understanding how they are regulated could lead to innovative ways to reduce the severity and spread of diseases. Here, we examine how host circadian rhythms influence rhythms in the asexual replication of malaria parasites. Asexual replication is responsible for the severity of malaria and fuels transmission of the disease, yet, how parasite rhythms are driven remains a mystery. We perturbed feeding rhythms of hosts by 12 hours (i.e. diurnal feeding in nocturnal mice) to desynchronise the host’s peripheral oscillators from the central, light-entrained oscillator in the brain and their rhythmic outputs. We demonstrate that the rhythms of rodent malaria parasites in day-fed hosts become inverted relative to the rhythms of parasites in night-fed hosts. Our results reveal that the host’s peripheral rhythms (associated with the timing of feeding and metabolism), but not rhythms driven by the central, light-entrained circadian oscillator in the brain, determine the timing (phase) of parasite rhythms. Further investigation reveals that parasite rhythms correlate closely with blood glucose rhythms. In addition, we show that parasite rhythms resynchronise to the altered host feeding rhythms when food availability is shifted, which is not mediated through rhythms in the host immune system. Our observations suggest that parasites actively control their developmental rhythms. Finally, counter to expectation, the severity of disease symptoms expressed by hosts was not affected by desynchronisation of their central and peripheral rhythms. Our study at the intersection of disease ecology and chronobiology opens up a new

Exploring the potential of host-environment relationship in the control of schistosomiasis in Africa

NARCIS (Netherlands)

Monde, C.; Syampungani, S.; Brink, van den P.J.

2015-01-01

A number of human disease prevalences are supported by host-parasite-environment interactions. One such disease is schistosomiasis. Schistosoma parasites are transmitted between the snail intermediate hosts and mammalian definitive hosts in an aquatic environment. This host-environment link

Guinea pig-adapted foot-and-mouth disease virus with altered receptor recognition can productively infect a natural host.

Science.gov (United States)

Núñez, José I; Molina, Nicolas; Baranowski, Eric; Domingo, Esteban; Clark, Stuart; Burman, Alison; Berryman, Stephen; Jackson, Terry; Sobrino, Francisco

2007-08-01

We report that adaptation to infect the guinea pig did not modify the capacity of foot-and-mouth disease virus (FMDV) to kill suckling mice and to cause an acute and transmissible disease in the pig, an important natural host for this pathogen. Adaptive amino acid replacements (I(248)-->T in 2C, Q(44)-->R in 3A, and L(147)-->P in VP1), selected upon serial passages of a type C FMDV isolated from swine (biological clone C-S8c1) in the guinea pig, were maintained after virus multiplication in swine and suckling mice. However, the adaptive replacement L(147)-->P, next to the integrin-binding RGD motif at the GH loop in VP1, abolished growth of the virus in different established cell lines and modified its antigenicity. In contrast, primary bovine thyroid cell cultures could be productively infected by viruses with replacement L(147)-->P, and this infection was inhibited by antibodies to alphavbeta6 and by an FMDV-derived RGD-containing peptide, suggesting that integrin alphavbeta6 may be used as a receptor for these mutants in the animal (porcine, guinea pig, and suckling mice) host. Substitution T(248)-->N in 2C was not detectable in C-S8c1 but was present in a low proportion of the guinea pig-adapted virus. This substitution became rapidly dominant in the viral population after the reintroduction of the guinea pig-adapted virus into pigs. These observations illustrate how the appearance of minority variant viruses in an unnatural host can result in the dominance of these viruses on reinfection of the original host species.

Cyclical changes in seroprevalence of leptospirosis in California sea lions: endemic and epidemic disease in one host species?

Directory of Open Access Journals (Sweden)

St Leger Judy

2007-11-01

Full Text Available Abstract Background Leptospirosis is a zoonotic disease infecting a broad range of mammalian hosts, and is re-emerging globally. California sea lions (Zalophus californianus have experienced recurrent outbreaks of leptospirosis since 1970, but it is unknown whether the pathogen persists in the sea lion population or is introduced repeatedly from external reservoirs. Methods We analyzed serum samples collected over an 11-year period from 1344 California sea lions that stranded alive on the California coast, using the microscopic agglutination test (MAT for antibodies to Leptospira interrogans serovar Pomona. We evaluated seroprevalence among yearlings as a measure of incidence in the population, and characterized antibody persistence times based on temporal changes in the distribution of titer scores. We conducted multinomial logistic regression to determine individual risk factors for seropositivity with high and low titers. Results The serosurvey revealed cyclical patterns in seroprevalence to L. interrogans serovar Pomona, with 4–5 year periodicity and peak seroprevalence above 50%. Seroprevalence in yearling sea lions was an accurate index of exposure among all age classses, and indicated on-going exposure to leptospires in non-outbreak years. Analysis of titer decay rates showed that some individuals probably maintain high titers for more than a year following exposure. Conclusion This study presents results of an unprecedented long-term serosurveillance program in marine mammals. Our results suggest that leptospirosis is endemic in California sea lions, but also causes periodic epidemics of acute disease. The findings call into question the classical dichotomy between maintenance hosts of leptospirosis, which experience chronic but largely asymptomatic infections, and accidental hosts, which suffer acute illness or death as a result of disease spillover from reservoir species.

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.

Effect of selective T cell depletion of host and/or donor bone marrow on lymphopoietic repopulation, tolerance, and graft-vs-host disease in mixed allogeneic chimeras (B10 + B10.D2----B10)

International Nuclear Information System (INIS)

Ildstad, S.T.; Wren, S.M.; Bluestone, J.A.; Barbieri, S.A.; Stephany, D.; Sachs, D.H.

1986-01-01

Reconstitution of lethally irradiated mice with a mixture of T cell-depleted syngeneic plus T cell-depleted allogeneic bone marrow (B10 + B10.D2----B10) leads to the induction of mixed lymphopoietic chimerism, excellent survivals, specific in vivo transplantation tolerance to subsequent donor strain skin grafts, and specific in vitro unresponsiveness to allogeneic donor lymphoid elements as assessed by mixed lymphocyte reaction (MLR) proliferative and cell-mediated lympholysis (CML) cytotoxicity assays. When B10 recipient mice received mixed marrow inocula in which the syngeneic component had not been T cell depleted, whether or not the allogeneic donor marrow was treated, they repopulated exclusively with host-type cells, promptly rejected donor-type skin allografts, and were reactive in vitro to the allogeneic donor by CML and MLR assays. In contrast, T cell depletion of the syngeneic component of the mixed marrow inocula resulted in specific acceptance of allogeneic donor strain skin grafts. Such animals were specifically unreactive to allogeneic donor lymphoid elements in vitro by CML and MLR, but were reactive to third party. When both the syngeneic and allogeneic marrow were T cell depleted, variable percentages of host- and donor-type lymphoid elements were detected in the mixed reconstituted host. When only the syngeneic bone marrow was T cell depleted, animals repopulated exclusively with donor-type cells. Although these animals had detectable in vitro anti-host (B10) reactivity by CML and MLR and reconstituted as fully allogeneic chimeras, they exhibited excellent survival and had no in vivo evidence for graft-vs-host disease. Experiments in which untreated donor spleen cells were added to the inocula in this last group suggest that the presence of T cell-depleted syngeneic bone marrow cells diminishes graft-vs-host disease and the mortality from it

A novel Capsicum gene inhibits host-specific disease resistance to Phytophthora capsici.

Science.gov (United States)

Reeves, Gregory; Monroy-Barbosa, Ariadna; Bosland, Paul W

2013-05-01

A novel disease resistance inhibitor gene (inhibitor of P. capsici resistance [Ipcr]), found in the chile pepper (Capsicum annuum) variety 'New Mexico Capsicum Accession 10399' (NMCA10399), inhibits resistance to Phytophthora capsici but not to other species of Phytophthora. When a highly P. capsici-resistant variety was hybridized with NMCA10399, the resultant F1 populations, when screened, were completely susceptible to P. capsici for root rot and foliar blight disease syndromes, despite the dominance inheritance of P. capsici resistance in chile pepper. The F2 population displayed a 3:13 resistant-to-susceptible (R:S) ratio. The testcross population displayed a 1:1 R:S ratio, and a backcross population to NMCA10399 displayed complete susceptibility. These results demonstrate the presence of a single dominant inhibitor gene affecting P. capsici resistance in chile pepper. Moreover, when lines carrying the Ipcr gene were challenged against six Phytophthora spp., the nonhost resistance was not overcome. Therefore, the Ipcr gene is interfering with host-specific resistance but not the pathogen- or microbe-associated molecular pattern nonhost responses.

Prediction of graft-versus-host disease in humans by donor gene-expression profiling.

Directory of Open Access Journals (Sweden)

Chantal Baron

2007-01-01

Full Text Available BACKGROUND: Graft-versus-host disease (GVHD results from recognition of host antigens by donor T cells following allogeneic hematopoietic cell transplantation (AHCT. Notably, histoincompatibility between donor and recipient is necessary but not sufficient to elicit GVHD. Therefore, we tested the hypothesis that some donors may be "stronger alloresponders" than others, and consequently more likely to elicit GVHD. METHODS AND FINDINGS: To this end, we measured the gene-expression profiles of CD4(+ and CD8(+ T cells from 50 AHCT donors with microarrays. We report that pre-AHCT gene-expression profiling segregates donors whose recipient suffered from GVHD or not. Using quantitative PCR, established statistical tests, and analysis of multiple independent training-test datasets, we found that for chronic GVHD the "dangerous donor" trait (occurrence of GVHD in the recipient is under polygenic control and is shaped by the activity of genes that regulate transforming growth factor-beta signaling and cell proliferation. CONCLUSIONS: These findings strongly suggest that the donor gene-expression profile has a dominant influence on the occurrence of GVHD in the recipient. The ability to discriminate strong and weak alloresponders using gene-expression profiling could pave the way to personalized transplantation medicine.

Host Competence: An Organismal Trait to Integrate Immunology and Epidemiology.

Science.gov (United States)

Martin, Lynn B; Burgan, S C; Adelman, James S; Gervasi, Stephanie S

2016-12-01

The new fields of ecological immunology and disease ecology have begun to merge, and the classic fields of immunology and epidemiology are beginning to blend with them. This merger is occurring because the integrative study of host-parasite interactions is providing insights into disease in ways that traditional methods have not. With the advent of new tools, mathematical and technological, we could be on the verge of developing a unified theory of infectious disease, one that supersedes the barriers of jargon and tradition. Here we argue that a cornerstone of any such synthesis will be host competence, the propensity of an individual host to generate new infections in other susceptible hosts. In the last few years, the emergence of systems immunology has led to novel insight into how hosts control or eliminate pathogens. Most such efforts have stopped short of considering transmission and the requisite behaviors of infected individuals that mediate it, and few have explicitly incorporated ecological and evolutionary principles. Ultimately though, we expect that the use of a systems immunology perspective will help link suborganismal processes (i.e., health of hosts and selection on genes) to superorganismal outcomes (i.e., community-level disease dynamics and host-parasite coevolution). Recently, physiological regulatory networks (PRNs) were cast as whole-organism regulatory systems that mediate homeostasis and hence link suborganismal processes with the fitness of individuals. Here, we use the PRN construct to develop a roadmap for studying host competence, taking guidance from systems immunology and evolutionary ecology research. We argue that PRN variation underlies heterogeneity in individual host competence and hence host-parasite dynamics. © The Author 2016. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Does host complement kill Borrelia burgdorferi within ticks?

Science.gov (United States)

Rathinavelu, Sivaprakash; Broadwater, Anne; de Silva, Aravinda M

2003-02-01

The Lyme disease spirochete, Borrelia burgdorferi, inhabits the gut lumen of the tick vector. At this location the spirochete is exposed to host blood when a tick feeds. We report here on studies that were done with normal and complement-deficient (C3-knockout) mice to determine if the host complement system killed spirochetes within the vector. We found that spirochete numbers within feeding nymphs were not influenced by complement, most likely because host complement was inactivated within the vector. The Lyme disease outer surface protein A (OspA) vaccine is a transmission-blocking vaccine that targets spirochetes in the vector. In experiments with mice hyperimmunized with OspA, complement was not required to kill spirochetes within nymphs and to block transmission from nymphs to the vaccinated host. However, host complement did enhance the ability of OspA antibody to block larvae from acquiring spirochetes. Thus, the effects of OspA antibody on nymphal transmission and larval acquisition appear to be based on different mechanisms.

Presentations and treatment of childhood scleroderma: localized scleroderma, eosinophilic fasciitis, systemic sclerosis, and graft-versus-host disease.

Science.gov (United States)

Hedrich, Christian Michael; Fiebig, Barbara; Hahn, Gabriele; Suttorp, Meinolf; Gahr, Manfred

2011-07-01

Juvenile scleroderma is a rare connective tissue disease that involves the skin and subcutaneous tissue. Among all presentations of juvenile scleroderma, localized scleroderma (JLSc) is the most frequent, followed by systemic disease (JSSc) and eosinophilic fasciitis (EF). In posttransplantation chronic graft-versus-host disease (GvHD), scleroderma-like skin involvement can occur. Systemic forms of juvenile scleroderma and GvHD can affect the internal organs, such as the lungs, the gastrointestinal tract, the heart, and kidneys and cause disability and severe, sometimes lethal, complications. Here, the authors give an overview of different presentations of juvenile scleroderma. They report their experience with the different forms and presentations of scleroderma, diagnostic workups, treatment, and outcome of all forms of childhood scleroderma in the context of the existing literature.

Soluble Interleukin-7 receptor levels and risk of acute graft-versus-disease after allogeneic haematopoietic stem cell transplantation

DEFF Research Database (Denmark)

Kielsen, Katrine; Shamim, Zaiba; Thiant, Stephanie

2018-01-01

Interleukin-7 is a cytokine essential for T cell homeostasis. IL-7 binds to cellular IL-7 receptors in competition with a soluble form of the receptor (sIL-7Rα). We hypothesized that altered sIL-7Rα levels may cause adverse outcomes in patients undergoing HSCT. In parallel, we investigated...... the impact of the IL-7Rα SNP rs6897932, which has been associated with release of IL-7R.The sIL-7Rα levels decreased during HSCT (from 114. ng/ml before to 48. ng/ml at day +. 14 (P sIL-7Rα ratio at day +. 14 was significantly higher...... in patients developing grade II-IV aGVHD (OR = 4.3, P = 0.026). Furthermore, donor carriage of the rs6897932 T allele was associated with reduced sIL-7Rα levels, increased risk of grades II-IV aGVHD (OR = 2.4, P = 0.055) and increased transplant-related mortality (CC = 4.5%, CT = 21.4% and TT = 27.3%, P = 0...

Skin ulcers related to chronic graft-versus-host disease: clinical findings and associated morbidity.

Science.gov (United States)

Jachiet, M; de Masson, A; Peffault de Latour, R; Rybojad, M; Robin, M; Bourhis, J-H; Xhaard, A; Dhedin, N; Sicre de Fontbrune, F; Suarez, F; Barete, S; Parquet, N; Nguyen, S; Ades, L; Rubio, M-T; Wittnebel, S; Bagot, M; Socié, G; Bouaziz, J-D

2014-07-01

According to the National Institutes of Health classification of chronic graft-versus-host disease (cGVHD), skin ulcers after allogeneic haematopoietic stem-cell transplantation (HSCT) are recorded as having the maximal severity score but published data are scarce. To describe skin ulcers related to cGVHD with an emphasis on clinical findings, associated morbidity, management and evolution. A multicentre retrospective analysis was carried out of patients with a diagnosis of cGVHD skin ulcers. All 25 patients included in the study had sclerotic skin cGVHD and 21 had lichenoid skin lesions associated with the sclerotic skin lesions. Thirteen patients had severe cGVHD without considering the skin, because of the involvement of an extracutaneous organ by cGVHD. The median time from HSCT to the onset of ulcers was 44 months. In addition to scleroderma, initial skin lesions at the site of ulcers were bullous erosive lichen in 21 patients and bullous erosive morphoea in four patients. Fifteen patients had an inaugural oedema. Ulcers were mostly bilateral with a predilection for the lower limbs. They were frequently colonized but few infections occurred. Four patients died during a median follow-up period of 55 months. Chronic graft-versus-host disease skin ulcers occur in patients with sclerodermatous skin cGVHD, are associated with severe cGVHD, often start with bullous lichenoid lesions or bullous morphoea and seem to cause more morbidity than mortality, given the low rate of mortality observed in our series of patients. © 2014 British Association of Dermatologists.

Host genetic variation impacts microbiome composition across human body sites.

Science.gov (United States)

Blekhman, Ran; Goodrich, Julia K; Huang, Katherine; Sun, Qi; Bukowski, Robert; Bell, Jordana T; Spector, Timothy D; Keinan, Alon; Ley, Ruth E; Gevers, Dirk; Clark, Andrew G

2015-09-15

The composition of bacteria in and on the human body varies widely across human individuals, and has been associated with multiple health conditions. While microbial communities are influenced by environmental factors, some degree of genetic influence of the host on the microbiome is also expected. This study is part of an expanding effort to comprehensively profile the interactions between human genetic variation and the composition of this microbial ecosystem on a genome- and microbiome-wide scale. Here, we jointly analyze the composition of the human microbiome and host genetic variation. By mining the shotgun metagenomic data from the Human Microbiome Project for host DNA reads, we gathered information on host genetic variation for 93 individuals for whom bacterial abundance data are also available. Using this dataset, we identify significant associations between host genetic variation and microbiome composition in 10 of the 15 body sites tested. These associations are driven by host genetic variation in immunity-related pathways, and are especially enriched in host genes that have been previously associated with microbiome-related complex diseases, such as inflammatory bowel disease and obesity-related disorders. Lastly, we show that host genomic regions associated with the microbiome have high levels of genetic differentiation among human populations, possibly indicating host genomic adaptation to environment-specific microbiomes. Our results highlight the role of host genetic variation in shaping the composition of the human microbiome, and provide a starting point toward understanding the complex interaction between human genetics and the microbiome in the context of human evolution and disease.

Commensal Bacteroides species induce colitis in host-genotype-specific fashion in a mouse model of inflammatory bowel disease.

Science.gov (United States)

Bloom, Seth M; Bijanki, Vinieth N; Nava, Gerardo M; Sun, Lulu; Malvin, Nicole P; Donermeyer, David L; Dunne, W Michael; Allen, Paul M; Stappenbeck, Thaddeus S

2011-05-19

The intestinal microbiota is important for induction of inflammatory bowel disease (IBD). IBD is associated with complex shifts in microbiota composition, but it is unclear whether specific bacterial subsets induce IBD and, if so, whether their proportions in the microbiota are altered during disease. Here, we fulfilled Koch's postulates in host-genotype-specific fashion using a mouse model of IBD with human-relevant disease-susceptibility mutations. From screening experiments we isolated common commensal Bacteroides species, introduced them into antibiotic-pretreated mice, and quantitatively reisolated them in culture. The bacteria colonized IBD-susceptible and -nonsusceptible mice equivalently, but induced disease exclusively in susceptible animals. Conversely, commensal Enterobacteriaceae were >100-fold enriched during spontaneous disease, but an Enterobacteriaceae isolate failed to induce disease in antibiotic-pretreated mice despite robust colonization. We thus demonstrate that IBD-associated microbiota alterations do not necessarily reflect underlying disease etiology. These findings establish important experimental criteria and a conceptual framework for understanding microbial contributions to IBD. Copyright © 2011 Elsevier Inc. All rights reserved.

Commensal Bacteroides species induce colitis in host-genotype-specific fashion in a mouse model of inflammatory bowel disease

Science.gov (United States)

Bloom, Seth M.; Bijanki, Vinieth N.; Nava, Gerardo M.; Sun, Lulu; Malvin, Nicole P.; Donermeyer, David L.; Dunne, W. Michael; Allen, Paul M.; Stappenbeck, Thaddeus S.

2011-01-01

SUMMARY The intestinal microbiota is important for induction of inflammatory bowel disease (IBD). IBD is associated with complex shifts in microbiota composition, but it is unclear whether specific bacterial subsets induce IBD and, if so, whether their proportions in the microbiota are altered during disease. Here we fulfilled Koch’s postulates in host-genotype-specific fashion using a mouse model of IBD with human-relevant disease-susceptibility mutations. From screening experiments we isolated common commensal Bacteroides species, introduced them into antibiotic-pretreated mice, and quantitatively re-isolated them in culture. The bacteria colonized IBD-susceptible and non-susceptible mice equivalently, but induced disease exclusively in susceptible animals. Conversely, commensal Enterobacteriaceae were >100-fold enriched during spontaneous disease but an Enterobacteriaceae isolate failed to induce disease in antibiotic-pretreated mice despite robust colonization. We thus demonstrate that IBD-associated microbiota alterations do not necessarily reflect underlying disease etiology. These findings establish important experimental criteria and a conceptual framework for understanding microbial contributions to IBD. PMID:21575910

Cell Therapy in Parkinson's Disease: Host Brain Repair Machinery Gets a Boost From Stem Cell Grafts.

Science.gov (United States)

Napoli, Eleonora; Borlongan, Cesar V

2017-06-01

This commentary highlights the major findings and future research directions arising from the recent publication by Zuo and colleagues in Stem Cells 2017 (in press). Here, we discuss the novel observations that transplanted human neural stem cells can induce endogenous brain repair by specifically stimulating a host of regenerative processes in the neurogenic niche (i.e., subventricular zone [SVZ]) in an animal model of Parkinson's disease. That the identified therapeutic proteomes, neurotrophic factors, and anti-inflammatory cytokines in the SVZ may facilitate brain regeneration and behavioral recovery open a new venue of research for our understanding of the pathology and treatment of Parkinson's disease. Stem Cells 2017;35:1443-1445. © 2017 AlphaMed Press.

Bacterial adhesion to host tissues : mechanisms and consequences

National Research Council Canada - National Science Library

Wilson, Michael, 1947

2002-01-01

"This book is about the adhesion of bacteria to their human hosts. Although adhesion is essential for maintaining members of the normal microflora in/on their host, it is also the crucial first stage in any infectious disease...

Mast Cell Stabilizers as Host Modulatory Drugs to Prevent and Control Periodontal Disease

Directory of Open Access Journals (Sweden)

Dhoom Singh Mehta

2011-01-01

Full Text Available Introduction: Mast cells are among the first cells to get in-volved in periodontal inflammation. Their numbers have been shown to be in-creased in cases of gingivitis and periodontal disease. The hypothesis: Since mast cell stabilizers like sodium cromogly-cate (SCG and nedocromil sodium (NS have been used in the prophylaxis of bronchial asthma without any significant adverse effects and also the fact that drugs like SCG show significant anti-inflammatory activities, it would be logical to use mast cell stabilizers as host modulating drugs for the treatment and prevention of peri-odontal disease. Evaluation of the hypothesis: Safety and efficacy of both SCG and NS are well documented. So, it will be systemically safe to use in humans. However, oral administration SCG or delivery of the drug by means local irrigation will not be very useful because SCG may not be secreted in the gingival crevicular fluid (GCF(as in the case of oral administraion or the drug may get washed out from periodontal pocket due to the constant flow of GCF(as in the case of irrigation. A local or targeted drug delivery of mast cell stabilizers can be used in patients with periodontal disease. Role of mast cells in periodontal disease has been dealt in-depth in many studies and articles. However, limited amount of research has been done on using mast cell stabilizers in the prevention and control of periodontal diseases. More studies are needed to study the efficacy and effective-ness of mast cell stabilizers as an adjunct to phase I therapy in the control of periodontal disease.

On the definition and utilization of heritable variation among hosts in reproduction ratio R0 for infectious diseases.

Science.gov (United States)

Anche, M T; de Jong, M C M; Bijma, P

2014-10-01

Infectious diseases have a major role in evolution by natural selection and pose a worldwide concern in livestock. Understanding quantitative genetics of infectious diseases, therefore, is essential both for understanding the consequences of natural selection and for designing artificial selection schemes in agriculture. The basic reproduction ratio, R0, is the key parameter determining risk and severity of infectious diseases. Genetic improvement for control of infectious diseases in host populations should therefore aim at reducing R0. This requires definitions of breeding value and heritable variation for R0, and understanding of mechanisms determining response to selection. This is challenging, as R0 is an emergent trait arising from interactions among individuals in the population. Here we show how to define breeding value and heritable variation for R0 for genetically heterogeneous host populations. Furthermore, we identify mechanisms determining utilization of heritable variation for R0. Using indirect genetic effects, next-generation matrices and a SIR (Susceptible, Infected and Recovered) model, we show that an individual's breeding value for R0 is a function of its own allele frequencies for susceptibility and infectivity and of population average susceptibility and infectivity. When interacting individuals are unrelated, selection for individual disease status captures heritable variation in susceptibility only, yielding limited response in R0. With related individuals, however, there is a secondary selection process, which also captures heritable variation in infectivity and additional variation in susceptibility, yielding substantially greater response. This shows that genetic variation in susceptibility represents an indirect genetic effect. As a consequence, response in R0 increased substantially when interacting individuals were genetically related.

T cell reconstitution in allogeneic haematopoietic stem cell transplantation

DEFF Research Database (Denmark)

Kielsen, K; Jordan, K K; Uhlving, H H

2015-01-01

Infections and acute graft-versus-host disease (aGVHD) are major causes of treatment-related mortality and morbidity following allogeneic haematopoietic stem cell transplantation (HSCT). Both complications depend on reconstitution of the T-lymphocyte population based on donor T cells. Although...... it is well established that Interleukin-7 (IL-7) is a cytokine essential for de novo T cell development in the thymus and homoeostatic peripheral expansion of T cells, associations between circulating levels of IL-7 and T cell reconstitution following HSCT have not been investigated previously. We...... in patients treated with anti-thymocyte globulin (ATG) compared with those not treated with ATG (P = 0.0079). IL-7 levels at day +7 were negatively associated with T cell counts at day +30 to +60 (at day +60: CD3(+) : β = -10.6 × 10(6) cells/l, P = 0.0030; CD8(+) : β = -8.4 × 10(6) cells/l, P = 0.061; CD4...

A case of membranous nephropathy as a manifestation of graft-versus-host disease

Directory of Open Access Journals (Sweden)

Jae Hyun Han

2013-03-01

Full Text Available Nephrotic syndrome (NS rarely occurs after hematopoietic stem cell transplantation (HSCT as a late manifestation of graft-versus-host disease (GVHD. Herein, we report a case of HSCT-associated membranous nephropathy in a female patient with aplastic anemia. The patient received an allogeneic HSCT from her human leukocyte antigen-identical brother following myeloablative conditioning chemotherapy. NS occurred 21 months after HSCT without any concurrent features of chronic GVHD. The patient was treated with prednisolone and cyclosporine after renal biopsy confirmed membranous nephropathy, and achieved complete remission. Our report contradicts previous assumptions that concomitant chronic GVHD is responsible for the development of NS, suggesting that NS can develop as a new, independent manifestation of GVHD.

Diagnostic Potential of Novel Salivary Host Biomarkers as Candidates for the Immunological Diagnosis of Tuberculosis Disease and Monitoring of Tuberculosis Treatment Response.

Science.gov (United States)

Jacobs, Ruschca; Maasdorp, Elizna; Malherbe, Stephanus; Loxton, Andre G; Stanley, Kim; van der Spuy, Gian; Walzl, Gerhard; Chegou, Novel N

2016-01-01

There is an urgent need for new tools for the early diagnosis of TB disease and monitoring of the response to treatment, especially in resource-constrained settings. We investigated the usefulness of host markers detected in saliva as candidate biomarkers for the immunological diagnosis of TB disease and monitoring of treatment response. We prospectively collected saliva samples from 51 individuals that presented with signs and symptoms suggestive of TB disease at a health centre in Cape Town, South Africa, prior to the establishment of a clinical diagnosis. Patients were later classified as having TB disease or other respiratory disease (ORD), using a combination of clinical, radiological and laboratory findings. We evaluated the concentrations of 69 host markers in saliva samples using a multiplex cytokine platform, and assessed the diagnostic potentials of these markers by receiver operator characteristics (ROC) curve analysis, and general discriminant analysis. Out of the 51 study participants, 18 (35.4%) were diagnosed with TB disease and 12 (23.5%) were HIV infected. Only two of the 69 host markers that were evaluated (IL-16 and IL-23) diagnosed TB disease individually with area under the ROC curve ≥0.70. A five-marker biosignature comprising of IL-1β, IL-23, ECM-1, HCC1 and fibrinogen diagnosed TB disease with a sensitivity of 88.9% (95% CI,76.7-99.9%) and specificity of 89.7% (95% CI, 60.4-96.6%) after leave-one-out cross validation, regardless of HIV infection status. Eight-marker biosignatures performed with a sensitivity of 100% (95% CI, 83.2-100%) and specificity of 95% (95% CI, 68.1-99.9%) in the absence of HIV infection. Furthermore, the concentrations of 11 of the markers changed during treatment, indicating that they may be useful in monitoring of TB treatment response. We have identified novel salivary biosignatures which may be useful in the diagnosis of TB disease and monitoring of the response to TB treatment. Our findings require further

Advance in Targeted Immunotherapy for Graft-Versus-Host Disease

Directory of Open Access Journals (Sweden)

Lingling Zhang

2018-05-01

Full Text Available Graft-versus-host disease (GVHD is a serious and deadly complication of patients, who undergo hematopoietic stem cell transplantation (HSCT. Despite prophylactic treatment with immunosuppressive agents, 20–80% of recipients develop acute GVHD after HSCT. And the incidence rates of chronic GVHD range from 6 to 80%. Standard therapeutic strategies are still lacking, although considerable advances have been gained in knowing of the predisposing factors, pathology, and diagnosis of GVHD. Targeting immune cells, such as regulatory T cells, as well as tolerogenic dendritic cells or mesenchymal stromal cells (MSCs display considerable benefit in the relief of GVHD through the deletion of alloactivated T cells. Monoclonal antibodies targeting cytokines or signaling molecules have been demonstrated to be beneficial for the prevention of GVHD. However, these remain to be verified in clinical therapy. It is also important and necessary to consider adopting individualized treatment based on GVHD subtypes, pathological mechanisms involved and stages. In the future, it is hoped that the identification of novel therapeutic targets and systematic research strategies may yield novel safe and effective approaches in clinic to improve outcomes of GVHD further. In this article, we reviewed the current advances in targeted immunotherapy for the prevention of GVHD.

Viral pathogen production in a wild grass host driven by host growth and soil nitrogen.

Science.gov (United States)

Whitaker, Briana K; Rúa, Megan A; Mitchell, Charles E

2015-08-01

Nutrient limitation is a basic ecological constraint that has received little attention in studies on virus production and disease dynamics. Nutrient availability could directly limit the production of viral nucleic acids and proteins, or alternatively limit host growth and thus indirectly limit metabolic pathways necessary for viral replication. In order to compare direct and indirect effects of nutrient limitation on virus production within hosts, we manipulated soil nitrogen (N) and phosphorus (P) availability in a glasshouse for the wild grass host Bromus hordeaceus and the viral pathogen Barley yellow dwarf virus-PAV. We found that soil N additions increased viral concentrations within host tissues, and the effect was mediated by host growth. Specifically, in statistical models evaluating the roles of host biomass production, leaf N and leaf P, viral production depended most strongly on host biomass, rather than the concentration of either nutrient. Furthermore, at low soil N, larger plants supported greater viral concentrations than smaller ones, whereas at high N, smaller plants supported greater viral concentrations. Our results suggest that enhanced viral productivity under N enrichment is an indirect consequence of nutrient stimulation to host growth rate. Heightened pathogen production in plants has important implications for a world facing increasing rates of nutrient deposition. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

VirHostNet 2.0: surfing on the web of virus/host molecular interactions data.

Science.gov (United States)

Guirimand, Thibaut; Delmotte, Stéphane; Navratil, Vincent

2015-01-01

VirHostNet release 2.0 (http://virhostnet.prabi.fr) is a knowledgebase dedicated to the network-based exploration of virus-host protein-protein interactions. Since the previous VirhostNet release (2009), a second run of manual curation was performed to annotate the new torrent of high-throughput protein-protein interactions data from the literature. This resource is shared publicly, in PSI-MI TAB 2.5 format, using a PSICQUIC web service. The new interface of VirHostNet 2.0 is based on Cytoscape web library and provides a user-friendly access to the most complete and accurate resource of virus-virus and virus-host protein-protein interactions as well as their projection onto their corresponding host cell protein interaction networks. We hope that the VirHostNet 2.0 system will facilitate systems biology and gene-centered analysis of infectious diseases and will help to identify new molecular targets for antiviral drugs design. This resource will also continue to help worldwide scientists to improve our knowledge on molecular mechanisms involved in the antiviral response mediated by the cell and in the viral strategies selected by viruses to hijack the host immune system. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

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 ...

Bactericidal/Permeability-increasing protein fold-containing family member A1 in airway host protection and respiratory disease.

Science.gov (United States)

Britto, Clemente J; Cohn, Lauren

2015-05-01

Bactericidal/permeability-increasing protein fold-containing family member A1 (BPIFA1), formerly known as SPLUNC1, is one of the most abundant proteins in respiratory secretions and has been identified with increasing frequency in studies of pulmonary disease. Its expression is largely restricted to the respiratory tract, being highly concentrated in the upper airways and proximal trachea. BPIFA1 is highly responsive to airborne pathogens, allergens, and irritants. BPIFA1 actively participates in host protection through antimicrobial, surfactant, airway surface liquid regulation, and immunomodulatory properties. Its expression is modulated in multiple lung diseases, including cystic fibrosis, chronic obstructive pulmonary disease, respiratory malignancies, and idiopathic pulmonary fibrosis. However, the role of BPIFA1 in pulmonary pathogenesis remains to be elucidated. This review highlights the versatile properties of BPIFA1 in antimicrobial protection and its roles as a sensor of environmental exposure and regulator of immune cell function. A greater understanding of the contribution of BPIFA1 to disease pathogenesis and activity may clarify if BPIFA1 is a biomarker and potential drug target in pulmonary disease.

Virus-host interactions and their roles in coral reef health and disease.

Science.gov (United States)

Thurber, Rebecca Vega; Payet, Jérôme P; Thurber, Andrew R; Correa, Adrienne M S

2017-04-01

Coral reefs occur in nutrient-poor shallow waters, constitute biodiversity and productivity hotspots, and are threatened by anthropogenic disturbance. This Review provides an introduction to coral reef virology and emphasizes the links between viruses, coral mortality and reef ecosystem decline. We describe the distinctive benthic-associated and water-column- associated viromes that are unique to coral reefs, which have received less attention than viruses in open-ocean systems. We hypothesize that viruses of bacteria and eukaryotes dynamically interact with their hosts in the water column and with scleractinian (stony) corals to influence microbial community dynamics, coral bleaching and disease, and reef biogeochemical cycling. Last, we outline how marine viruses are an integral part of the reef system and suggest that the influence of viruses on reef function is an essential component of these globally important environments.

Shifts in diversification rates and host jump frequencies shaped the diversity of host range among Sclerotiniaceae fungal plant pathogens.

Science.gov (United States)

Navaud, Olivier; Barbacci, Adelin; Taylor, Andrew; Clarkson, John P; Raffaele, Sylvain

2018-03-01

The range of hosts that a parasite can infect in nature is a trait determined by its own evolutionary history and that of its potential hosts. However, knowledge on host range diversity and evolution at the family level is often lacking. Here, we investigate host range variation and diversification trends within the Sclerotiniaceae, a family of Ascomycete fungi. Using a phylogenetic framework, we associate diversification rates, the frequency of host jump events and host range variation during the evolution of this family. Variations in diversification rate during the evolution of the Sclerotiniaceae define three major macro-evolutionary regimes with contrasted proportions of species infecting a broad range of hosts. Host-parasite cophylogenetic analyses pointed towards parasite radiation on distant hosts long after host speciation (host jump or duplication events) as the dominant mode of association with plants in the Sclerotiniaceae. The intermediate macro-evolutionary regime showed a low diversification rate, high frequency of duplication events and the highest proportion of broad host range species. Our findings suggest that the emergence of broad host range fungal pathogens results largely from host jumps, as previously reported for oomycete parasites, probably combined with low speciation rates. These results have important implications for our understanding of fungal parasites evolution and are of particular relevance for the durable management of disease epidemics. © 2018 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.

Stress responses in Streptococcus species and their effects on the host.

Science.gov (United States)

Nguyen, Cuong Thach; Park, Sang-Sang; Rhee, Dong-Kwon

2015-11-01

Streptococci cause a variety of diseases, such as dental caries, pharyngitis, meningitis, pneumonia, bacteremia, endocarditis, erysipelas, and necrotizing fasciitis. The natural niche of this genus of bacteria ranges from the mouth and nasopharynx to the skin, indicating that the bacteria will inevitably be subjected to environmental changes during invasion into the host, where it is exposed to the host immune system. Thus, the Streptococcus-host interaction determines whether bacteria are cleared by the host's defenses or whether they survive after invasion to cause serious diseases. If this interaction was to be deciphered, it could aid in the development of novel preventive and therapeutic agents. Streptococcus species possess many virulent factors, such as peroxidases and heat-shock proteins (HSPs), which play key roles in protecting the bacteria from hostile host environments. This review will discuss insights into the mechanism(s) by which streptococci adapt to host environments. Additionally, we will address how streptococcal infections trigger host stress responses; however, the mechanism by which bacterial components modulate host stress responses remains largely unknown.

Acute graft-versus-host disease of the gut: considerations for the gastroenterologist.

Science.gov (United States)

Naymagon, Steven; Naymagon, Leonard; Wong, Serre-Yu; Ko, Huaibin Mabel; Renteria, Anne; Levine, John; Colombel, Jean-Frederic; Ferrara, James

2017-12-01

Haematopoietic stem cell transplantation (HSCT) is central to the management of many haematological disorders. A frequent complication of HSCT is acute graft-versus-host disease (GVHD), a condition in which immune cells from the donor attack healthy recipient tissues. The gastrointestinal system is among the most common sites affected by acute GVHD, and severe manifestations of acute GVHD of the gut portends a poor prognosis in patients after HSCT. Acute GVHD of the gastrointestinal tract presents both diagnostic and therapeutic challenges. Although the clinical manifestations are nonspecific and overlap with those of infection and drug toxicity, diagnosis is ultimately based on clinical criteria. As reliable serum biomarkers have not yet been validated outside of clinical trials, endoscopic and histopathological evaluation continue to be utilized in diagnosis. Once a diagnosis of gastrointestinal acute GVHD is established, therapy with systemic corticosteroids is typically initiated, and non-responders can be treated with a wide range of second-line therapies. In addition to treating the underlying disease, the management of complications including profuse diarrhoea, severe malnutrition and gastrointestinal bleeding is paramount. In this Review, we discuss strategies for the diagnosis and management of acute GVHD of the gastrointestinal tract as they pertain to the practising gastroenterologist.

Genetics of simple and complex host-parasite interactions

International Nuclear Information System (INIS)

Sidhu, G.S.; Webster, J.M.

1977-01-01

In nature a host plant can be viewed as a miniature replica of an ecological system where true and incidental parasites share the same habitat. Consequently, they influence each other's presence directly by interspecific interaction, and indirectly by inducing changes in the host's physiology and so form disease complexes. Since all physiological phenomena have their counterpart in the respective genetic systems of interacting organisms, valuable genetic information can be derived from the analysis of complex parasitic systems. Disease complexes may be classified according to the nature of interaction between various parasites on the same host. One parasite may nullify the host's resistance to another (e.g. Tomato - Meloidogyne incognita + Fusarium oxysporum lycopersici system). Conversely, a parasite may invoke resistance in the host against another parasite (e.g. Tomato - Fusarium oxysporum lycopersici + Verticillium albo atrum system). From the study of simple parasitic systems we know that resistance versus susceptibility against a single parasite is normally monogenically controlled. However, when more than one parasite interacts to invoke or nullify each other's responses on the same host plant, the genetic results suggest epistatic ratios. Nevertheless, epistatic ratios have been obtained also from simple parasitic systems owing to gene interaction. The epistatic ratios obtained from complex and simple parasitic systems are contrasted and compared. It is suggested that epistatic ratios obtained from simple parasitic systems may, in fact, be artifacts resulting from complex parasitic associations that often occur in nature. Polygenic inheritance and the longevity of a cultivar is also discussed briefly in relation to complex parasitic associations. Induced mutations can play a significant role in the study of complex parasitic associations, and thus can be very useful in controlling plant diseases

Chlamydia infection across host species boundaries promotes distinct sets of transcribed anti-apoptotic factors.

Directory of Open Access Journals (Sweden)

Joshua eMessinger

2015-12-01

Full Text Available Chlamydiae, obligate intracellular bacteria, cause significant human and veterinary associated diseases. Having emerged an estimated 700-million years ago, these bacteria have twice adapted to humans as a host species, causing sexually transmitted infection (C. trachomatis and respiratory associated disease (C. pneumoniae. The principle mechanism of host cell defense against these intracellular bacteria is the induction of cell death via apoptosis. However, in the arms race of co-evolution, Chlamydiae have developed mechanisms to promote cell viability and inhibit cell death. Herein we examine the impact of Chlamydiae infection across multiple host species on transcription of anti-apoptotic genes. We found mostly distinct patterns of gene expression (Mcl1 and cIAPs elicited by each pathogen-host pair indicating Chlamydiae infection across host species boundaries does not induce a universally shared host response. Understanding species specific host-pathogen interactions is paramount to deciphering how potential pathogens become emerging diseases.

Host homeostatic responses to alcohol-induced cellular stress in animal models of alcoholic liver disease.

Science.gov (United States)

Wang, He Joe; Murray, Gary J; Jung, Mary Katherine

2015-01-01

Humans develop various clinical phenotypes of severe alcoholic liver disease, including alcoholic hepatitis and cirrhosis, generally after decades of heavy drinking. In such individuals, following each episode of drinking, their livers experience heightened intracellular and extracellular stresses that are closely associated with alcohol consumption and alcohol metabolism. This article focuses on the latest advances made in animal models on evolutionarily conserved homeostatic mechanisms for coping with and resolving these stress conditions. The mechanisms discussed include the stress-activated protein kinase JNK, energy regulator AMPK, autophagy and the inflammatory response. Over time, the host may respond variably to stress with protective mechanisms that are critical in determining an individual's vulnerability to developing severe alcoholic liver disease. A systematic review of these mechanisms and their temporal changes in animal models provides the basis for general conclusions, and raises questions for future studies. The relevance of these data to human conditions is also discussed.

Hologenomics: Systems-Level Host Biology.

Science.gov (United States)

Theis, Kevin R

2018-01-01

The hologenome concept of evolution is a hypothesis explaining host evolution in the context of the host microbiomes. As a hypothesis, it needs to be evaluated, especially with respect to the extent of fidelity of transgenerational coassociation of host and microbial lineages and the relative fitness consequences of repeated associations within natural holobiont populations. Behavioral ecologists are in a prime position to test these predictions because they typically focus on animal phenotypes that are quantifiable, conduct studies over multiple generations within natural animal populations, and collect metadata on genetic relatedness and relative reproductive success within these populations. Regardless of the conclusion on the hologenome concept as an evolutionary hypothesis, a hologenomic perspective has applied value as a systems-level framework for host biology, including in medicine. Specifically, it emphasizes investigating the multivarious and dynamic interactions between patient genomes and the genomes of their diverse microbiota when attempting to elucidate etiologies of complex, noninfectious diseases.

Brazilian situation of blood component irradiation practice for the prevention of transfusion associated Graft-versus-Host disease

International Nuclear Information System (INIS)

Goes, E.G.; Borges, J.C.; Covas, D.T.; Motta, I.

1998-01-01

Transfusion-associated graft-versus-host disease (TA-GVHD) is a usually complication of transfusion of blood component containing T lymphocytes what recently has also involved immunocompetent patient. Gamma irradiation of cellular blood components has been the mainstay against TA-GVHD, nevertheless there is little information in the literature about current transfusion medicine practices regarding gamma irradiation of blood products. This work presents an overview of the Brazilian reality and suggests policies to optimize TA-GVHD prevention. (Author)

Brazilian situation of blood component irradiation practice for the prevention of transfusion associated Graft-versus-Host disease

Energy Technology Data Exchange (ETDEWEB)

Goes, E.G.; Borges, J.C. [EE/COPPE-UFRJ (Brazil); Covas, D.T. [Faculdade deMedicina-USP-RP (Brazil); Motta, I. [Instituto Nacional do Cancer- Rio deJaneiro (Brazil)

1998-12-31

Transfusion-associated graft-versus-host disease (TA-GVHD) is a usually complication of transfusion of blood component containing T lymphocytes what recently has also involved immunocompetent patient. Gamma irradiation of cellular blood components has been the mainstay against TA-GVHD, nevertheless there is little information in the literature about current transfusion medicine practices regarding gamma irradiation of blood products. This work presents an overview of the Brazilian reality and suggests policies to optimize TA-GVHD prevention. (Author)

Does Host Complement Kill Borrelia burgdorferi within Ticks?

OpenAIRE

Rathinavelu, Sivaprakash; Broadwater, Anne; de Silva, Aravinda M.

2003-01-01

The Lyme disease spirochete, Borrelia burgdorferi, inhabits the gut lumen of the tick vector. At this location the spirochete is exposed to host blood when a tick feeds. We report here on studies that were done with normal and complement-deficient (C3-knockout) mice to determine if the host complement system killed spirochetes within the vector. We found that spirochete numbers within feeding nymphs were not influenced by complement, most likely because host complement was inactivated within ...

Photobiomodulation Therapy Alleviates Tissue Fibroses Associated with Chronic Graft-Versus-Host Disease: Two Case Reports and Putative Anti-Fibrotic Roles of TGF-

NARCIS (Netherlands)

Epstein, Joel B.; Raber-Durlacher, Judith E.; Huysmans, Marie-Charlotte; Schoordijk, Maria C. E.; Cheng, Jerry E.; Bensadoun, Rene-Jean; Arany, Praveen R.

2018-01-01

Objective: Patients who receive allogeneic hematopoietic stem cell transplantation may experience oral complications due to chronic graft-versus-host disease (cGVHD). The manifestations may include progressive sclerosis-like changes that may involve various body sites, including the oropharynx.

Small hypoxia-primed mesenchymal stem cells attenuate graft-versus-host disease

KAUST Repository

Kim, YongHwan

2018-05-22

Mesenchymal stem cells (MSCs) are of particular interest for the treatment of immune-related diseases due to their immunosuppressive capacity. Here, we show that Small MSCs primed with Hypoxia and Calcium ions (SHC-MSCs) exhibit enhanced stemness and immunomodulatory functions for treating allogeneic conflicts. Compared with naïve cultured human umbilical cord blood-derived MSCs, SHC-MSCs were resistant to passage-dependent senescence mediated via the monocyte chemoattractant protein-1 and p53/p21 cascade and secreted large amounts of pro-angiogenic and immunomodulatory factors, resulting in suppression of T-cell proliferation. SHC-MSCs showed DNA demethylation in pluripotency, germline, and imprinted genes similarly to very small embryonic-like stem cells, suggesting a potential mutual relationship. Genome-wide DNA methylome and transcriptome analyses indicated that genes related to immune modulation, cell adhesion, and the cell cycle were up-regulated in SHC-MSCs. Particularly, polo-like kinase-1 (PLK1), zinc-finger protein-143, dehydrogenase/reductase-3, and friend-of-GATA2 play a key role in the beneficial effects of SHC-MSCs. Administration of SHC-MSCs or PLK1-overexpressing MSCs significantly ameliorated symptoms of graft-versus-host disease (GVHD) in a humanized mouse model, resulting in significantly improved survival, less weight loss, and reduced histopathologic injuries in GVHD target organs compared with naïve MSC-infused mice. Collectively, our findings suggest that SHC-MSCs can improve the clinical treatment of allogeneic conflicts, including GVHD.

Ocular manifestations of graft-versus-host disease: 10 years’ experience

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Lin X

2015-07-01

Full Text Available Xihui Lin, Harrison Dwight Cavanagh Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX, USA Purpose: To evaluate the ocular presentation, treatment, and clinical course of graft-versus-host disease (GVHD. Design: Retrospective case series. Participants: Two hundred and forty-nine patients with systemic GVHD were included in the study. Methods: Ocular and systemic data were collected from 2003 to 2013. Main outcome measures: Mortality, visual acuity, and response of ocular symptoms. Results: Sixty-four patients had ocular manifestations (25.7%. At presentation, the mean age was 44.5 years and mean latency was 16.4 months. The most common presentations were keratoconjunctivitis sicca, cataract, blepharitis, ocular hypertension, and filamentary keratitis. Visual acuity at presentation was 20/49; at the worst point in the disease was 20/115; and at most recent visit was 20/63. When topical anti-inflammatory drops were used in addition to tears, 54.3% of patients’ ocular symptoms stabilized. When autologous serum was used in addition, 80% stabilized. The overall 10-year mortality of GVHD was 29.7%. For those with ocular involvement, it was 21.9%. Conclusion: Systemic GVHD has a high mortality rate, but ocular involvement does not suggest a worse prognosis. The main ocular presentations were keratoconjunctivitis sicca, cataracts, and ocular hypertension. Dry eyes in this population were very severe with overall worsening in visual acuity. However, with a step-wise approach involving topical anti-inflammatory medications and autologous serum tears, ocular symptoms do improve. It is important to monitor these patients closely, as they are prone to serious ocular complications such as corneal perforation and endophthalmitis. Keywords: dry eye, keratitis, corneal ulceration

The trans-generational impact of population density signals on host-parasite interactions.

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Michel, Jessica; Ebert, Dieter; Hall, Matthew D

2016-11-25

The density of a host population is a key parameter underlying disease transmission, but it also has implications for the expression of disease through its effect on host physiology. In response to higher densities, individuals are predicted to either increase their immune investment in response to the elevated risk of parasitism, or conversely to decrease their immune capacity as a consequence of the stress of a crowded environment. However, an individual's health is shaped by many different factors, including their genetic background, current environmental conditions, and maternal effects. Indeed, population density is often sensed through the presence of info-chemicals in the environment, which may influence a host's interaction with parasites, and also those of its offspring. All of which may alter the expression of disease, and potentially uncouple the presumed link between changes in host density and disease outcomes. In this study, we used the water flea Daphnia magna and its obligate bacterial parasite Pasteuria ramosa, to investigate how signals of high host density impact on host-parasite interactions over two consecutive generations. We found that the chemical signals from crowded treatments induced phenotypic changes in both the parental and offspring generations. In the absence of a pathogen, life-history changes were genotype-specific, but consistent across generations, even when the signal of density was removed. In contrast, the influence of density on infected animals depended on the trait and generation of exposure. When directly exposed to signals of high-density, host genotypes responded differently in how they minimised the severity of disease. Yet, in the subsequent generation, the influence of density was rarely genotype-specific and instead related to ability of the host to minimise the onset of infection. Our findings reveal that population level correlations between host density and infection capture only part of the complex relationship

Clinical approach in the management of oral chronic graft-versus-host disease (cGVHD) in a series of specialized medical centers

DEFF Research Database (Denmark)

Elad, Sharon; Jensen, Siri Beier; Raber-Durlacher, Judith E

2015-01-01

BACKGROUND: The oral cavity is frequently affected in chronic graft-versus-host disease (cGVHD), with variable clinical presentations. The literature on the effective management of patients suffering from oral cGVHD is limited. OBJECTIVE: The objective of this study was to assess the clinical app...

Human regulatory T cells control xenogeneic graft-versus-host disease induced by autologous T cells in RAG2-/-gammac-/- immunodeficient mice.

NARCIS (Netherlands)

Mutis, T; Rijn, R.S. van; Simonetti, E.R.; Aarts-Riemens, T.; Emmelot, M.E.; Bloois, L. van; Martens, A.; Verdonck, L.F.; Ebeling, S.B.

2006-01-01

PURPOSE: Effective prevention of graft-versus-host disease (GvHD) is a major challenge to improve the safety of allogeneic stem cell transplantation for leukemia treatment. In murine transplantation models, administration of naturally occurring CD4+CD25+ regulatory T cells (Treg) can prevent GvHD.

Localization of sclerotic-type chronic graft-vs-host disease to sites of skin injury: potential insight into the mechanism of isomorphic and isotopic responses.

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Martires, Kathryn J; Baird, Kristin; Citrin, Deborah E; Hakim, Fran T; Pavletic, Steven Z; Cowen, Edward W

2011-09-01

The mechanisms responsible for the variable manifestations of chronic cutaneous graft-vs-host disease (cGVHD) are poorly understood. Localization of sclerotic-type chronic graft-vs-host disease to sites of skin injury (isomorphic and isotopic responses), a recognized phenomenon in morphea, suggests a potential common pathway between cGVHD and other sclerotic skin conditions. Four cases of sclerotic-type cGVHD developed at the site of disparate skin injuries (ionizing radiotherapy, repeated needle sticks, central catheter site, and varicella-zoster virus infection). We review the spectrum of previously reported cases of sclerotic and nonsclerotic cGVHD relating to external forces on the skin. Localization of sclerotic-type cGVHD may occur after many types of skin injury, including UV and ionizing radiotherapy, needle sticks, viral infection, and pressure or friction. Recognition of this phenomenon may be helpful for the early diagnosis of sclerotic disease. Recent insights into the immunological consequences of minor skin injury may provide important clues to the underlying pathogenesis of cGVHD-mediated skin disease.

A reservoir of drug-resistant pathogenic bacteria in asymptomatic hosts.

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Gabriel G Perron

Full Text Available The population genetics of pathogenic bacteria has been intensively studied in order to understand the spread of disease and the evolution of virulence and drug resistance. However, much less attention has been paid to bacterial carriage populations, which inhabit hosts without producing disease. Since new virulent strains that cause disease can be recruited from the carriage population of bacteria, our understanding of infectious disease is seriously incomplete without knowledge on the population structure of pathogenic bacteria living in an asymptomatic host. We report the first extensive survey of the abundance and diversity of a human pathogen in asymptomatic animal hosts. We have found that asymptomatic swine from livestock productions frequently carry populations of Salmonella enterica with a broad range of drug-resistant strains and genetic diversity greatly exceeding that previously described. This study shows how agricultural practice and human intervention may lead and influence the evolution of a hidden reservoir of pathogens, with important implications for human health.

Effects of two doses of anti-T lymphocyte globulin-Fresenius given after full-match sibling stem cell transplantation in acute myeloblastic leukemia patients who underwent myeloablative fludarabine/busulfan conditioning.

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Boga, Can; Yeral, Mahmut; Gereklioglu, Ciğdem; Asma, Suheyl; Maytalman, Erkan; Aytan, Pelin; Kozanoglu, Ilknur; Sariturk, Cagla; Ozdogu, Hakan

2018-02-20

Anti-T lymphocyte globulin Fresenius (rATG-F; ATG-Fresenius) and antithymocyte globulin (thymoglobulin), which are included in transplant protocols, are used to reduce the risk of chronic graft-versus-host disease (cGVHD) or suppress allograft rejection. Available clinical studies have been conducted in heterogenous patient populations and with different administration protocols including stem cell sources. Additionally, the pharmacokinetics of ATG is variable, and the clinically effective dose of rATG-F, in particular, is not exactly known. The aim of the study was to investigate the clinical outcomes of acute myeloid leukemia (AML) patients who underwent hemopoietic peripheral stem cell transplantation from full-matched sibling donors and given two different doses of r-ATG-F. This was a single-center, retrospective chart review conducted between July 2005 and July 2016. Sixty-nine consecutive AML patients who underwent transplant with fludarabine- and busulfan-based conditioning were included in the study. Patients in Group 1 received 15 mg/kg body weight rATG-F to 2013 (n = 46), and Group 2 received 30 mg/kg of rATG-F dose begining in 2013 to reduce to cGVHD (n = 23). Cyclosporine and methotrexate were used to treat acute GVHD (aGVHD) prophylaxis. Outcome parameters were compared between the groups. Although the recommended dose r-ATG-F had led to a decrease in the cumulative incidence of cGVHD (27 [58.7%] vs. 8 [34.8%]; p = .03), it also increased the infection rate at 1 year (3 [6.5%] vs. 4 [17.4%]; p = .02). The two groups were similar in terms of engraftment time, aGVHD, relapse, nonrelapse mortality, and rATG-F-related toxicity. A Cox regression model revealed that aGVHD III-IV was associated with increased nonrelapse mortality at 1 year (hazard ratio = 18.2; 95% confidence interval, 1.667-199.255; p = <.02). No patients developed rATG-F-related severe adverse events (Common Terminology Criteria grade 4 or 5). Dose difference of

Reduction of fatal graft-versus-host disease by 3H--thymidine suicide of donor cells cultured with host cells

International Nuclear Information System (INIS)

Cheever, M.A.; Einstein, A.B. Jr.; Kempf, R.A.; Fefer, A.

1977-01-01

The effect of the tritiated thymidine ( 3 H-TdR) suicide technique on the ability of donor cells to induce fatal graft-versus-host disease (GVHD) was studied. C57BL/6 (H-2/sup b/) spleen cells were stimulated in vitro with irradiated BALB/c (H-2/sup d/) Moloney lymphoma cells in mixed culture and 3 H-TdR of high-specific activity added to eliminate proliferating cells. The ability of such cells to induce fatal GVHD was assayed by injecting them i.v. into adult BALB/c mice immunosuppressed with cyclophosphamide (180 mg/kg). These cells induced fatal GVHD in fewer mice (52 percent) than did C57BL/6 cells cultured with BALB/c lymphoma cells but without 3 H-TdR (87 percent) and C57BL/6 cells cultured with irradiated C57BL/6 cells with (95 percent) or without 3 H-TdR (86 percent). Thus, the 3 H-TdR suicide technique greatly diminished the ability of cells to induce lethal GVHD

Ultraviolet irradiation modulates MHC-alloreactive cytotoxic T-cell precursors involved in the onset of graft-versus-host disease

International Nuclear Information System (INIS)

Prooijen, H.C. Van; Aarts-Riemens, M.I.; Weelden, H. Van; Grijzenhout, M.A.

1992-01-01

Ultraviolet B (UVB) irradiation of cellular blood components has been proposed as a new technology to prevent HLA sensitization in recipients. Earlier studies have shown that a dose of 2 J/cm 2 abrogates the ability of lymphocytes to serve as stimulators in mixed lymphocyte cultures (MLC). In this study the authors evaluate the effect of UV energy on T-lymphocytes for the prevention of transfusion-associated graft-versus-host disease (TA-GvHD). The response of cytotoxic T-lymphocyte precursors against host alloantigens was almost undetectable at a dose of 0.5 J/cm 2 . T-cell proliferation in MLC or in response to phytohaemagglutinin was inhibited by more than 95% at doses of 1 J/cm 2 or higher. The data suggest that UV irradiation can be used to prevent both HLA sensitization and TA-GvHD in recipients. (Author)

The contribution of different prion protein types and host polymorphisms to clinicopathological variations in Creutzfeldt-Jakob disease.

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Head, Mark W; Ironside, James W

2012-07-01

Creutzfeldt-Jakob disease is a fatal neurodegenerative disease that primarily affects the central nervous system. In this respect, it can be considered alongside the more frequently occurring neurodegenerative diseases, such as Alzheimer's disease. Creutzfeldt-Jakob disease is perhaps the paradigmatic protein misfolding disorder, so comparisons between the mechanisms involved in Creutzfeldt-Jakob disease and other neurodegenerative diseases associated with protein misfolding (such as the tauopathies and synucleinopathies) may also be informative. Like many of these diseases, Creutzfeldt-Jakob disease occurs sporadically or can, more rarely, be associated with mutations. However, Creutzfeldt-Jakob disease can also be acquired and is experimentally transmissible. These properties have had profound public health implications and made the disease of interest to virologists, in addition to those interested in protein misfolding disorders and neurodegeneration. The possible causes for the pronounced phenotypic variation among different forms of Creutzfeldt-Jakob disease are beginning to become understood, and these appear to depend in large measure on the genetics of the host (specifically the sequence of the prion protein gene, PRNP) and the epigenetic aspects of the agent (thought to be a misfolded and aggregated form of the PRNP gene product, termed a prion). This review will examine whether this model in its present form has sufficient complexity and subtlety to account for the clinicopathological variation evident in Creutzfeldt-Jakob disease and will outline the ways in which a more complete and informative molecular definition of human prions are currently being sought. Copyright © 2012 John Wiley & Sons, Ltd.

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

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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.

Reversal of CD8 T-Cell–Mediated Mucocutaneous Graft-Versus-Host-Like Disease by the JAK Inhibitor Tofacitinib

Science.gov (United States)

Okiyama, Naoko; Furumoto, Yasuko; Villarroel, Vadim A; Linton, Jay T; Tsai, Wanxia L; Gutermuth, Jan; Ghoreschi, Kamran; Gadina, Massimo; O'Shea, John J; Katz, Stephen I

2014-01-01

The utility of allogeneic hematopoietic stem cell transplantation is limited by graft-versus-host disease (GVHD), a significant cause of morbidity and mortality. Patients with GVHD exhibit cutaneous manifestations with histological features of interface dermatitis followed by scleroderma-like changes. JAK inhibitors represent a class of immunomodulatory drugs that inhibit signaling by multiple cytokines. Herein we report the effects of tofacitinib in a murine model of GVHD. Oral administration of tofacitinib prevented GVHD-like disease manifested by weight loss and mucocutaneous lesions. More importantly, tofacitinib was also effective in reversing established disease. Tofacitinib diminished the expansion and activation of murine CD8 T cells in this model, and had similar effects on IL-2-stimulated human CD8 T cells. Tofacitinib also inhibited the expression of IFN-γ-inducible chemoattractants by keratinocytes, and IFN-γ-inducible cell death of keratinocytes. Tofacitinib may be an effective drug for treatment against CD8 T-cell–mediated mucocutaneous diseases in patients with GVHD. PMID:24213371

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.

The role of gut microbiota in health and disease: In vitro modeling of host-microbe interactions at the aerobe-anaerobe interphase of the human gut.

Science.gov (United States)

von Martels, Julius Z H; Sadaghian Sadabad, Mehdi; Bourgonje, Arno R; Blokzijl, Tjasso; Dijkstra, Gerard; Faber, Klaas Nico; Harmsen, Hermie J M

2017-04-01

The microbiota of the gut has many crucial functions in human health. Dysbiosis of the microbiota has been correlated to a large and still increasing number of diseases. Recent studies have mostly focused on analyzing the associations between disease and an aberrant microbiota composition. Functional studies using (in vitro) gut models are required to investigate the precise interactions that occur between specific bacteria (or bacterial mixtures) and gut epithelial cells. As most gut bacteria are obligate or facultative anaerobes, studying their effect on oxygen-requiring human gut epithelial cells is technically challenging. Still, several (anaerobic) bacterial-epithelial co-culture systems have recently been developed that mimic host-microbe interactions occurring in the human gut, including 1) the Transwell "apical anaerobic model of the intestinal epithelial barrier", 2) the Host-Microbiota Interaction (HMI) module, 3) the "Human oxygen-Bacteria anaerobic" (HoxBan) system, 4) the human gut-on-a-chip and 5) the HuMiX model. This review discusses the role of gut microbiota in health and disease and gives an overview of the characteristics and applications of these novel host-microbe co-culture systems. Copyright © 2017 Elsevier Ltd. All rights reserved.

Host Defence to Pulmonary Mycosis

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Christopher H Mody

1999-01-01

Full Text Available OBJECTIVE: To provide a basic understanding of the mechanisms of host defense to pathogenic fungi. This will help physicians understand why some patients are predisposed to fungal infections and update basic scientists on how microbial immunology applies to fungal disease.

Vision-Related Quality of Life in Patients with Ocular Graft-versus-Host Disease.

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Saboo, Ujwala S; Amparo, Francisco; Abud, Tulio B; Schaumberg, Debra A; Dana, Reza

2015-08-01

To assess the vision-related quality of life (QOL) in a cohort of patients with ocular graft-versus-host disease (GVHD). Prospective study. Eighty-four patients diagnosed with chronic ocular GVHD. We assessed the vision-related QOL with the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25). The symptoms of ocular GVHD were assessed using the Ocular Surface Disease Index (OSDI) and Symptom Assessment in Dry Eye (SANDE) questionnaires. We assessed vision-related QOL with the NEI-VFQ-25 and compared the scores obtained from patients with ocular GVHD with those from a healthy population. In the ocular GVHD population, we also evaluated the associations between the NEI-VFQ-25 and the dry eye symptoms measured by the OSDI and SANDE questionnaires, age, duration of disease, best-corrected visual acuity (BCVA), corneal fluorescein staining (CFS), tear break-up time, and Schirmer test. The mean composite NEI-VFQ-25 score in patients with ocular GVHD was 76.5±17. Compared with healthy subjects, patients with ocular GVHD reported reduced scores on all NEI-VFQ-25 subscales (each P vision (P = 0.11). The NEI-VFQ-25 composite scores significantly correlated with OSDI (R = -0.81, P vision-related QOL. This study highlights the impact of ocular GVHD on the vision-related QOL, and thus the importance of comprehensive diagnosis and treatment of this condition. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Crimean-Congo Hemorrhagic Fever: Tick-Host-Virus Interactions

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Anna Papa

2017-05-01

Full Text Available Crimean-Congo hemorrhagic fever virus (CCHFV is transmitted to humans by bite of infected ticks or by direct contact with blood or tissues of viremic patients or animals. It causes to humans a severe disease with fatality up to 30%. The current knowledge about the vector-host-CCHFV interactions is very limited due to the high-level containment required for CCHFV studies. Among ticks, Hyalomma spp. are considered the most competent virus vectors. CCHFV evades the tick immune response, and following its replication in the lining of the tick's midgut, it is disseminated by the hemolymph in the salivary glands and reproductive organs. The introduction of salivary gland secretions into the host cells is the major route via which CCHFV enters the host. Following an initial amplification at the site of inoculation, the virus is spread to the target organs. Apoptosis is induced via both intrinsic and extrinsic pathways. Genetic factors and immune status of the host may affect the release of cytokines which play a major role in disease progression and outcome. It is expected that the use of new technology of metabolomics, transcriptomics and proteomics will lead to improved understanding of CCHFV-host interactions and identify potential targets for blocking the CCHFV transmission.

Host heterogeneity influences the impact of a non-native disease invasion on populations of a foundation tree species

Science.gov (United States)

Jules, Erik S.; Carroll, Allyson L.; Garcia, Andrea M.; Steenbock, Christopher M.; Kauffman, Matthew J.

2014-01-01

 P. lateralis causes profound impacts to population structure and the invasion outcome will be governed by the heterogeneity found in host size and location. Models of disease invasion will require an understanding of how heterogeneity influences spread dynamics to adequately predict the outcome for host populations.

Upfront haploidentical transplant for acquired severe aplastic anemia: registry-based comparison with matched related transplant.

Science.gov (United States)

Xu, Lan-Ping; Jin, Song; Wang, Shun-Qing; Xia, Ling-Hui; Bai, Hai; Gao, Su-Jun; Liu, Qi-Fa; Wang, Jian-Min; Wang, Xin; Jiang, Ming; Zhang, Xi; Wu, De-Pei; Huang, Xiao-Jun

2017-01-21

Haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT) is an alternative treatment method for severe aplastic anemia (SAA) patients lacking suitable identical donors and those who are refractory to immunosuppressive therapy (IST). The current study evaluated the feasibility of upfront haploidentical HSCT in SAA patients. We conducted a multicenter study based on a registry database. One hundred fifty-eight SAA patients who underwent upfront transplantation between June 2012 and September 2015 were enrolled. Eighty-nine patients had haploidentical donors (HIDs), and 69 had matched related donors (MRDs) for HSCT. The median times for myeloid engraftment in the HID and MRD cohorts were 12 (range, 9-20) and 11 (range, 8-19) days, with a cumulative incidence of 97.8 and 97.1% (P = 0.528), respectively. HID recipients had an increased cumulative incidence of grades II-IV acute graft-versus-host disease (aGVHD) (30.3 vs. 1.5%, P < 0.001), grades III-IV aGVHD (10.1 vs. 1.5%, P = 0.026), and chronic GVHD (cGVHD) (30.6 vs. 4.4%, P < 0.001) at 1 year but similar extensive cGVHD (3.4 vs. 0%, P = 0.426). The three-year estimated overall survival (OS) rates were 86.1 and 91.3% (P = 0.358), while the three-year estimated failure-free survival (FFS) rates were 85.0 and 89.8% (P = 0.413) in the HID and MRD cohorts, respectively. In multivariate analysis, survival outcome for the entire population was significantly adversely associated with increased transfusions and poor performance status pre-SCT. We did not observe differences in primary engraftment and survival outcomes by donor type. Haploidentical SCT as upfront therapy was an effective and safe option for SAA patients, with favorable outcomes in experienced centers.

[Mesenchymal stromal cells in the treatment of graft-versus-host disease: where do we stand?].

Science.gov (United States)

Schüle, Silke; Berger, André

2015-11-01

Medicinal products based on mesenchymal stromal cells (MSC) are expected to have a therapeutic benefit in a variety of conditions and, accordingly, are being tested in many clinical studies. The treatment and prevention of graft-versus-host disease (GVHD) is one of the world's most widely studied MSC therapy concepts. So far, one MSC medicinal product has been approved for the treatment of GvHD. This article gives an overview of the particular features related to the production of MSC-based medicinal products, the state of non-clinical research, and the clinical development status of MSCs and the associated challenges, especially in the context of GvHD.

Identification of host response signatures of infection.

Energy Technology Data Exchange (ETDEWEB)

Branda, Steven S.; Sinha, Anupama; Bent, Zachary

2013-02-01

Biological weapons of mass destruction and emerging infectious diseases represent a serious and growing threat to our national security. Effective response to a bioattack or disease outbreak critically depends upon efficient and reliable distinguishing between infected vs healthy individuals, to enable rational use of scarce, invasive, and/or costly countermeasures (diagnostics, therapies, quarantine). Screening based on direct detection of the causative pathogen can be problematic, because culture- and probe-based assays are confounded by unanticipated pathogens (e.g., deeply diverged, engineered), and readily-accessible specimens (e.g., blood) often contain little or no pathogen, particularly at pre-symptomatic stages of disease. Thus, in addition to the pathogen itself, one would like to detect infection-specific host response signatures in the specimen, preferably ones comprised of nucleic acids (NA), which can be recovered and amplified from tiny specimens (e.g., fingerstick draws). Proof-of-concept studies have not been definitive, however, largely due to use of sub-optimal sample preparation and detection technologies. For purposes of pathogen detection, Sandia has developed novel molecular biology methods that enable selective isolation of NA unique to, or shared between, complex samples, followed by identification and quantitation via Second Generation Sequencing (SGS). The central hypothesis of the current study is that variations on this approach will support efficient identification and verification of NA-based host response signatures of infectious disease. To test this hypothesis, we re-engineered Sandia's sophisticated sample preparation pipelines, and developed new SGS data analysis tools and strategies, in order to pioneer use of SGS for identification of host NA correlating with infection. Proof-of-concept studies were carried out using specimens drawn from pathogen-infected non-human primates (NHP). This work provides a strong foundation for

IL-17 Genetic and Immunophenotypic Evaluation in Chronic Graft-versus-Host Disease

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Renata Gonçalves Resende

2014-01-01

Full Text Available Although interleukin-17 (IL-17 is a recently discovered cytokine associated with several autoimmune diseases, its role in the pathogenesis of chronic graft-versus-host disease (cGVHD was not established yet. The objective of this study was to investigate the association of IL17A and IL17F genes polymorphisms and IL-17A and IL-17F levels with cGVHD. IL-17A expression was also investigated in CD4+ T cells of patients with systemic cGVHD. For Part I of the study, fifty-eight allo-HSCT recipients and donors were prospectively studied. Blood samples were obtained to determine IL17A and IL17F genes polymorphisms. Cytokines levels in blood and saliva were assessed by ELISA at days +35 and +100 after HSCT. In Part II, for the immunophenotypic evaluation, eight patients with systemic cGVHD were selected and the expression of IL-17A was evaluated. We found association between recipient AA genotype with systemic cGVHD. No association was observed between IL-17A levels and cGVHD. Lower IL-17A levels in the blood were associated with AA genotype. In flow cytometry analysis, decreased expression of IL-17A was observed in patients with cGVHD after stimulation. In conclusion, IL-17A may have an important role in the development of systemic cGVHD.

Emergency rabies control in a community of two high-density hosts

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Singer Alexander

2012-06-01

Full Text Available Abstract Background Rabies is a fatal viral disease that potentially can affect all mammals. Terrestrial rabies is not present in the United Kingdom and has been eliminated from Western Europe. Nevertheless the possibility remains that rabies could be introduced to England, where it would find two potentially suitable hosts, red foxes and badgers. With the aim to analyse the spread and emergency control of rabies in this two species host community, a simulation model was constructed. Different control strategies involving anti-rabies vaccination and population culling were developed, considering control application rates, spatial extent and timing. These strategies were evaluated for efficacy and feasibility to control rabies in hypothetical rural areas in the South of England immediately after a disease outbreak. Results The model confirmed that both fox and badger populations, separately, were competent hosts for the spread of rabies. Realistic vaccination levels were not sufficient to control rabies in high-density badger populations. The combined species community was a very strong rabies host. However, disease spread within species appeared to be more important than cross-species infection. Thus, the drivers of epidemiology depend on the potential of separate host species to sustain the disease. To control a rabies outbreak in the two species, both species had to be targeted. Realistic and robust control strategies involved vaccination of foxes and badgers, but also required badger culling. Although fox and badger populations in the UK are exceptionally dense, an outbreak of rabies can be controlled with a higher than 90% chance, if control response is quick and follows a strict regime. This requires surveillance and forceful and repeated control campaigns. In contrast, an uncontrolled rabies outbreak in the South of England would quickly develop into a strong epizootic involving tens of thousands of rabid foxes and badgers. Conclusions If

New Insight for the Diagnosis of Gastrointestinal Acute Graft-versus-Host Disease

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Florent Malard

2014-01-01

Full Text Available Allogeneic stem cell transplantation (allo-SCT is a curative therapy for different life-threatening malignant and nonmalignant hematologic disorders. Graft-versus-host disease (GVHD remains a major source of morbidity and mortality following allo-SCT, which limits the use of this treatment in a broader spectrum of patients. Early diagnostic of GVHD is essential to initiate treatment as soon as possible. Unfortunately, the diagnosis of GVHD may be difficult to establish, because of the nonspecific nature of the associated symptoms and of the numerous differential diagnosis. This is particularly true regarding gastrointestinal (GI acute GVHD. In the recent years many progress has been made in medical imaging test and endoscopic techniques. The interest of these different techniques in the diagnosis of GI acute GVHD has been evaluated in several studies. With this background we review the contributions, limitations, and future prospect of these techniques in the diagnosis of GI acute GVHD.

Dual analysis of the murine cytomegalovirus and host cell transcriptomes reveal new aspects of the virus-host cell interface.

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Vanda Juranic Lisnic

Full Text Available Major gaps in our knowledge of pathogen genes and how these gene products interact with host gene products to cause disease represent a major obstacle to progress in vaccine and antiviral drug development for the herpesviruses. To begin to bridge these gaps, we conducted a dual analysis of Murine Cytomegalovirus (MCMV and host cell transcriptomes during lytic infection. We analyzed the MCMV transcriptome during lytic infection using both classical cDNA cloning and sequencing of viral transcripts and next generation sequencing of transcripts (RNA-Seq. We also investigated the host transcriptome using RNA-Seq combined with differential gene expression analysis, biological pathway analysis, and gene ontology analysis. We identify numerous novel spliced and unspliced transcripts of MCMV. Unexpectedly, the most abundantly transcribed viral genes are of unknown function. We found that the most abundant viral transcript, recently identified as a noncoding RNA regulating cellular microRNAs, also codes for a novel protein. To our knowledge, this is the first viral transcript that functions both as a noncoding RNA and an mRNA. We also report that lytic infection elicits a profound cellular response in fibroblasts. Highly upregulated and induced host genes included those involved in inflammation and immunity, but also many unexpected transcription factors and host genes related to development and differentiation. Many top downregulated and repressed genes are associated with functions whose roles in infection are obscure, including host long intergenic noncoding RNAs, antisense RNAs or small nucleolar RNAs. Correspondingly, many differentially expressed genes cluster in biological pathways that may shed new light on cytomegalovirus pathogenesis. Together, these findings provide new insights into the molecular warfare at the virus-host interface and suggest new areas of research to advance the understanding and treatment of cytomegalovirus

Photobiomodulation therapy alleviates tissue fibroses associated with chronic Graft-Versus-Host Disease : Two case reports and putative anti-fibrotic roles of TGF-β

NARCIS (Netherlands)

Epstein, J.B.; Raber-Durlacher, J.E.; Huysmans, M.C.; Schoordijk, M.C.E.; Cheng, J.E.; Bensadoun, R.J.; Arany, P.R.

2018-01-01

Objective: Patients who receive allogeneic hematopoietic stem cell transplantation may experience oral complications due to chronic graft-versus-host disease (cGVHD). The manifestations may include progressive sclerosis-like changes that may involve various body sites, including the oropharynx.

Effects of land use on zoonotic host communities: a global correlative analysis

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Rory Gibb, MRes

2018-05-01

Full Text Available Background: Environmental trade-offs associated with land use—for example, between food security and biodiversity conservation—are crucial dimensions of planetary health. Land use-driven biodiversity change might predictably affect disease risk if reservoir host species are consistently more likely to persist under human disturbance (ie, if ecological communities in modified habitats generally have a higher zoonotic potential than those in unmodified habitats. Such a phenomenon has been observed in specific disease systems, but with substantial change in global land use projected for this century, assessing its global and taxonomic generality would shed light on an important hypothesised driver of environmental synergies or trade-offs between conservation and public health. Methods: We collated data on hosts of human parasites and pathogens from the published literature, and combined these with the Projecting Responses of Ecological Diversity in Changing Terrestrial Systems (PREDICTS global database of local ecological communities and associated land use data. We analysed the effects of land use on host richness and abundance across 7330 sites globally, controlling for disease-related research effort and differences in survey methods. Findings: Ecological communities in anthropogenic land uses (managed and urban ecosystems contained a consistently higher richness and abundance of host species than did communities in nearby primary (undisturbed sites. However, among mammal hosts of zoonotic pathogens, we found considerable taxonomic variation in host responses to land use, with abundances of rodents and bats generally increasing and those of primates and carnivores generally declining in modified landscapes. Interpretation: Our results suggest that future change in global land use has the potential to drive overall increasing contact between people and ecological communities with increased shared pathogen potential (ie, more potential hosts

Models of marine molluscan diseases: Trends and challenges.

Science.gov (United States)

Powell, Eric N; Hofmann, Eileen E

2015-10-01

Disease effects on host population dynamics and the transmission of pathogens between hosts are two important challenges for understanding how epizootics wax and wane and how disease influences host population dynamics. For the management of marine shellfish resources, marine diseases pose additional challenges in early intervention after the appearance of disease, management of the diseased population to limit a decline in host abundance, and application of measures to restrain that decline once it occurs. Mathematical models provide one approach for quantifying these effects and addressing the competing goals of managing the diseased population versus managing the disease. The majority of models for molluscan diseases fall into three categories distinguished by these competing goals. (1) Models that consider disease effects on the host population tend to focus on pathogen proliferation within the host. Many of the well-known molluscan diseases are pandemic, in that they routinely reach high prevalence rapidly over large geographic expanses, are characterized by transmission that does not depend upon a local source, and exert a significant influence on host population dynamics. Models focused on disease proliferation examine the influence of environmental change on host population metrics and provide a basis to better manage diseased stocks. Such models are readily adapted to questions of fishery management and habitat restoration. (2) Transmission models are designed to understand the mechanisms triggering epizootics, identify factors impeding epizootic development, and evaluate controls on the rate of disease spread over the host's range. Transmission models have been used extensively to study terrestrial diseases, yet little attention has been given to their potential for understanding the epidemiology of marine molluscan diseases. For management of diseases of wild stocks, transmission models open up a range of options, including the application of area

Investigating intra-host and intra-herd sequence diversity of foot-and-mouth disease virus.

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King, David J; Freimanis, Graham L; Orton, Richard J; Waters, Ryan A; Haydon, Daniel T; King, Donald P

2016-10-01

Due to the poor-fidelity of the enzymes involved in RNA genome replication, foot-and-mouth disease (FMD) virus samples comprise of unique polymorphic populations. In this study, deep sequencing was utilised to characterise the diversity of FMD virus (FMDV) populations in 6 infected cattle present on a single farm during the series of outbreaks in the UK in 2007. A novel RT-PCR method was developed to amplify a 7.6kb nucleotide fragment encompassing the polyprotein coding region of the FMDV genome. Illumina sequencing of each sample identified the fine polymorphic structures at each nucleotide position, from consensus level changes to variants present at a 0.24% frequency. These data were used to investigate population dynamics of FMDV at both herd and host levels, evaluate the impact of host on the viral swarm structure and to identify transmission links with viruses recovered from other farms in the same series of outbreaks. In 7 samples, from 6 different animals, a total of 5 consensus level variants were identified, in addition to 104 sub-consensus variants of which 22 were shared between 2 or more animals. Further analysis revealed differences in swarm structures from samples derived from the same animal suggesting the presence of distinct viral populations evolving independently at different lesion sites within the same infected animal. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Application of nuclear techniques in study of host parasite relationship and immunological control of parasite diseases of livestock in India- an overview

International Nuclear Information System (INIS)

Sharma, R.L.

1996-01-01

The objective of this review article was to make a realistic appraisal of scientific achievements in understanding host parasite relationship and in development of safe effective diagnosis of diseases caused by parasites. The article also enlists future prospects and areas of future study. 99 refs., 4 tabs

Pharmacogenetics of steroid-responsive acute graft-versus-host disease.

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Arora, Mukta; Weisdorf, Daniel J; Shanley, Ryan M; Thyagarajan, Bharat

2017-05-01

Glucocorticoids are central to effective therapy of acute graft-versus-host disease (GVHD). However, only about half of the patients respond to steroids in initial therapy. Based on postulated mechanisms for anti-inflammatory effectiveness, we explored genetic variations in glucocorticoid receptor, co-chaperone proteins, membrane transporters, inflammatory mediators, and variants in the T-cell receptor complex in hematopoietic cell transplant recipients with acute GVHD requiring treatment with steroids and their donors toward response at day 28 after initiation of therapy. A total of 300 recipient and donor samples were analyzed. Twenty-three SNPs in 17 genes affecting glucocorticoid pathways were included in the analysis. In multiple regression analysis, donor SNP rs3192177 in the ZAP70 gene (O.R. 2.8, 95% CI: 1.3-6.0, P=.008) and donor SNP rs34471628 in the DUSPI gene (O.R. 0.3, 95% CI: 0.1-1.0, P=.048) were significantly associated with complete or partial response. However, after adjustment for multiple testing, these SNPs did not remain statistically significant. Our results, on this small, exploratory, hypothesis generating analysis suggest that common genetic variation in glucocorticoid pathways may help identify subjects with differential response to glucocorticoids. This needs further assessment in larger datasets and if validated could help identify subjects for alternative treatments and design targeted treatments to overcome steroid resistance. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Simultaneous transcriptional profiling of bacteria and their host cells.

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Michael S Humphrys

Full Text Available We developed an RNA-Seq-based method to simultaneously capture prokaryotic and eukaryotic expression profiles of cells infected with intracellular bacteria. As proof of principle, this method was applied to Chlamydia trachomatis-infected epithelial cell monolayers in vitro, successfully obtaining transcriptomes of both C. trachomatis and the host cells at 1 and 24 hours post-infection. Chlamydiae are obligate intracellular bacterial pathogens that cause a range of mammalian diseases. In humans chlamydiae are responsible for the most common sexually transmitted bacterial infections and trachoma (infectious blindness. Disease arises by adverse host inflammatory reactions that induce tissue damage & scarring. However, little is known about the mechanisms underlying these outcomes. Chlamydia are genetically intractable as replication outside of the host cell is not yet possible and there are no practical tools for routine genetic manipulation, making genome-scale approaches critical. The early timeframe of infection is poorly understood and the host transcriptional response to chlamydial infection is not well defined. Our simultaneous RNA-Seq method was applied to a simplified in vitro model of chlamydial infection. We discovered a possible chlamydial strategy for early iron acquisition, putative immune dampening effects of chlamydial infection on the host cell, and present a hypothesis for Chlamydia-induced fibrotic scarring through runaway positive feedback loops. In general, simultaneous RNA-Seq helps to reveal the complex interplay between invading bacterial pathogens and their host mammalian cells and is immediately applicable to any bacteria/host cell interaction.

Graft versus host disease in the bone marrow, liver and thymus humanized mouse model.

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Matthew B Greenblatt

Full Text Available Mice bearing a "humanized" immune system are valuable tools to experimentally manipulate human cells in vivo and facilitate disease models not normally possible in laboratory animals. Here we describe a form of GVHD that develops in NOD/SCID mice reconstituted with human fetal bone marrow, liver and thymus (NS BLT mice. The skin, lungs, gastrointestinal tract and parotid glands are affected with progressive inflammation and sclerosis. Although all mice showed involvement of at least one organ site, the incidence of overt clinical disease was approximately 35% by 22 weeks after reconstitution. The use of hosts lacking the IL2 common gamma chain (NOD/SCID/γc(-/- delayed the onset of disease, but ultimately did not affect incidence. Genetic analysis revealed that particular donor HLA class I alleles influenced the risk for the development of GVHD. At a cellular level, GVHD is associated with the infiltration of human CD4+ T cells into the skin and a shift towards Th1 cytokine production. GVHD also induced a mixed M1/M2 polarization phenotype in a dermal murine CD11b+, MHC class II+ macrophage population. The presence of xenogenic GVHD in BLT mice both presents a major obstacle in the use of humanized mice and an opportunity to conduct preclinical studies on GVHD in a humanized model.

Interplay of host genetics and gut microbiota underlying the onset and clinical presentation of inflammatory bowel disease.

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Imhann, Floris; Vich Vila, Arnau; Bonder, Marc Jan; Fu, Jingyuan; Gevers, Dirk; Visschedijk, Marijn C; Spekhorst, Lieke M; Alberts, Rudi; Franke, Lude; van Dullemen, Hendrik M; Ter Steege, Rinze W F; Huttenhower, Curtis; Dijkstra, Gerard; Xavier, Ramnik J; Festen, Eleonora A M; Wijmenga, Cisca; Zhernakova, Alexandra; Weersma, Rinse K

2018-01-01

Patients with IBD display substantial heterogeneity in clinical characteristics. We hypothesise that individual differences in the complex interaction of the host genome and the gut microbiota can explain the onset and the heterogeneous presentation of IBD. Therefore, we performed a case-control analysis of the gut microbiota, the host genome and the clinical phenotypes of IBD. Stool samples, peripheral blood and extensive phenotype data were collected from 313 patients with IBD and 582 truly healthy controls, selected from a population cohort. The gut microbiota composition was assessed by tag-sequencing the 16S rRNA gene. All participants were genotyped. We composed genetic risk scores from 11 functional genetic variants proven to be associated with IBD in genes that are directly involved in the bacterial handling in the gut: NOD2 , CARD9 , ATG16L1 , IRGM and FUT2 . Strikingly, we observed significant alterations of the gut microbiota of healthy individuals with a high genetic risk for IBD: the IBD genetic risk score was significantly associated with a decrease in the genus Roseburia in healthy controls (false discovery rate 0.017). Moreover, disease location was a major determinant of the gut microbiota: the gut microbiota of patients with colonic Crohn's disease (CD) is different from that of patients with ileal CD, with a decrease in alpha diversity associated to ileal disease (p=3.28×10 -13 ). We show for the first time that genetic risk variants associated with IBD influence the gut microbiota in healthy individuals. Roseburia spp are acetate-to-butyrate converters, and a decrease has already been observed in patients with IBD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Hosts and vectors of Trypanosoma cruzi discrete typing units in the Chagas disease endemic region of the Paraguayan Chaco

OpenAIRE

ACOSTA, NIDIA; L?PEZ, ELSA; LEWIS, MICHAEL D.; LLEWELLYN, MARTIN S.; G?MEZ, ANA; ROM?N, FABIOLA; MILES, MICHAEL A.; YEO, MATTHEW

2017-01-01

SUMMARY Active Trypanosoma cruzi transmission persists in the Gran Chaco region, which is considered hyperendemic for Chagas disease. Understanding domestic and sylvatic transmission cycles and therefore the relationship between vectors and mammalian hosts is crucial to designing and implementing improved effective control strategies. Here we describe the species of triatomine vectors and the sylvatic mammal reservoirs of T. cruzi, in different localities of the Paraguayan and Bolivian Chaco....

Escaping deleterious immune response in their hosts: lessons from trypanosomatids

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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.

Friends or Foes? Host defense (antimicrobial) peptides and proteins in human skin diseases.

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Niyonsaba, François; Kiatsurayanon, Chanisa; Chieosilapatham, Panjit; Ogawa, Hideoki

2017-11-01

Host defense peptides/proteins (HDPs), also known as antimicrobial peptides/proteins (AMPs), are key molecules in the cutaneous innate immune system. AMPs/HDPs historically exhibit broad-spectrum killing activity against bacteria, enveloped viruses, fungi and several parasites. Recently, AMPs/HDPs were shown to have important biological functions, including inducing cell proliferation, migration and differentiation; regulating inflammatory responses; controlling the production of various cytokines/chemokines; promoting wound healing; and improving skin barrier function. Despite the fact that AMPs/HDPs protect our body, several studies have hypothesized that these molecules actively contribute to the pathogenesis of various skin diseases. For example, AMPs/HDPs play crucial roles in the pathological processes of psoriasis, atopic dermatitis, rosacea, acne vulgaris, systemic lupus erythematosus and systemic sclerosis. Thus, AMPs/HDPs may be a double-edged sword, promoting cutaneous immunity while simultaneously initiating the pathogenesis of some skin disorders. This review will describe the most common skin-derived AMPs/HDPs (defensins, cathelicidins, S100 proteins, ribonucleases and dermcidin) and discuss the biology and both the positive and negative aspects of these AMPs/HDPs in skin inflammatory/infectious diseases. Understanding the regulation, functions and mechanisms of AMPs/HDPs may offer new therapeutic opportunities in the treatment of various skin disorders. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Molecular pathological epidemiology of epigenetics: emerging integrative science to analyze environment, host, and disease.

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Ogino, Shuji; Lochhead, Paul; Chan, Andrew T; Nishihara, Reiko; Cho, Eunyoung; Wolpin, Brian M; Meyerhardt, Jeffrey A; Meissner, Alexander; Schernhammer, Eva S; Fuchs, Charles S; Giovannucci, Edward

2013-04-01

phenotype, LINE-1 (long interspersed nucleotide element-1; also called long interspersed nuclear element-1; long interspersed element-1; L1) hypomethylation, etc), and host-disease interactions. In this article, we illustrate increasing contribution of modern pathology to broader public health sciences, which attests pivotal roles of pathologists in the new integrated MPE science towards our ultimate goal of personalized medicine and prevention.

Host-parasite genotypic interactions in the honey bee: the dynamics of diversity.

Science.gov (United States)

Evison, Sophie E F; Fazio, Geraldine; Chappell, Paula; Foley, Kirsten; Jensen, Annette B; Hughes, William O H

2013-07-01

Parasites are thought to be a major driving force shaping genetic variation in their host, and are suggested to be a significant reason for the maintenance of sexual reproduction. A leading hypothesis for the occurrence of multiple mating (polyandry) in social insects is that the genetic diversity generated within-colonies through this behavior promotes disease resistance. This benefit is likely to be particularly significant when colonies are exposed to multiple species and strains of parasites, but host-parasite genotypic interactions in social insects are little known. We investigated this using honey bees, which are naturally polyandrous and consequently produce genetically diverse colonies containing multiple genotypes (patrilines), and which are also known to host multiple strains of various parasite species. We found that host genotypes differed significantly in their resistance to different strains of the obligate fungal parasite that causes chalkbrood disease, while genotypic variation in resistance to the facultative fungal parasite that causes stonebrood disease was less pronounced. Our results show that genetic variation in disease resistance depends in part on the parasite genotype, as well as species, with the latter most likely relating to differences in parasite life history and host-parasite coevolution. Our results suggest that the selection pressure from genetically diverse parasites might be an important driving force in the evolution of polyandry, a mechanism that generates significant genetic diversity in social insects.

HostPhinder: A Phage Host Prediction Tool

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Julia Villarroel

2016-05-01

Full Text Available The current dramatic increase of antibiotic resistant bacteria has revitalised the interest in bacteriophages as alternative antibacterial treatment. Meanwhile, the development of bioinformatics methods for analysing genomic data places high-throughput approaches for phage characterization within reach. Here, we present HostPhinder, a tool aimed at predicting the bacterial host of phages by examining the phage genome sequence. Using a reference database of 2196 phages with known hosts, HostPhinder predicts the host species of a query phage as the host of the most genomically similar reference phages. As a measure of genomic similarity the number of co-occurring k-mers (DNA sequences of length k is used. Using an independent evaluation set, HostPhinder was able to correctly predict host genus and species for 81% and 74% of the phages respectively, giving predictions for more phages than BLAST and significantly outperforming BLAST on phages for which both had predictions. HostPhinder predictions on phage draft genomes from the INTESTI phage cocktail corresponded well with the advertised targets of the cocktail. Our study indicates that for most phages genomic similarity correlates well with related bacterial hosts. HostPhinder is available as an interactive web service [1] and as a stand alone download from the Docker registry [2].

Mechanisms of Disease: Host-Pathogen Interactions between Burkholderia Species and Lung Epithelial Cells

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David, Jonathan; Bell, Rachel E.; Clark, Graeme C.

2015-01-01

Members of the Burkholderia species can cause a range of severe, often fatal, respiratory diseases. A variety of in vitro models of infection have been developed in an attempt to elucidate the mechanism by which Burkholderia spp. gain entry to and interact with the body. The majority of studies have tended to focus on the interaction of bacteria with phagocytic cells with a paucity of information available with regard to the lung epithelium. However, the lung epithelium is becoming more widely recognized as an important player in innate immunity and the early response to infections. Here we review the complex relationship between Burkholderia species and epithelial cells with an emphasis on the most pathogenic species, Burkholderia pseudomallei and Burkholderia mallei. The current gaps in knowledge in our understanding are highlighted along with the epithelial host-pathogen interactions that offer potential opportunities for therapeutic intervention. PMID:26636042

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.

Characterization of Regulatory Dendritic Cells That Mitigate Acute Graft-versus-Host Disease in Older Mice Following Allogeneic Bone Marrow Transplantation

OpenAIRE

Scroggins, Sabrina M.; Olivier, Alicia K.; Meyerholz, David K.; Schlueter, Annette J.

2013-01-01

Despite improvements in human leukocyte antigen matching and pharmacologic prophylaxis, acute graft-versus-host disease (GVHD) is often a fatal complication following hematopoietic stem cell transplant (HSCT). Older HSCT recipients experience significantly increased morbidity and mortality compared to young recipients. Prophylaxis with syngeneic regulatory dendritic cells (DCreg) in young bone marrow transplanted (BMT) mice has been shown to decrease GVHD-associated mortality. To evaluate thi...

A synthetic eicosanoid LX-mimetic unravels host-donor interactions in allogeneic BMT-induced GvHD to reveal an early protective role for host neutrophils.

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Devchand, Pallavi R; Schmidt, Birgitta A; Primo, Valeria C; Zhang, Qing-yin; Arnaout, M Amin; Serhan, Charles N; Nikolic, Boris

2005-02-01

Lipoxin A(4) (LXA(4)) and aspirin-triggered 15-epi-LXA(4) are potent endogenous lipid mediators thought to define the inflammatory set-point. We used single prophylactic administrations of a synthetic aspirin-triggered lipoxin A(4) signal mimetic, ATLa, to probe dynamics of early host-donor interactions in a mouse model for the inflammation-associated multifactorial disease of allogeneic bone marrow transplant (BMT) -induced graft-vs.-host disease (GvHD). We first demonstrated that both host and donor are responsive to the ATLa signals. The simple and restricted regimen of a single prophylactic administration of ATLa [100 ng/mL to donor cells or 1 microg (approximately 50 microg/kg) i.v. to host] was sufficient to delay death. Clinical indicators of weight, skin lesions, diarrhea and eye inflammation were monitored. Histological analyses on day 45 post-BMT showed that the degree of cellular trafficking, particularly neutrophil infiltrate, and protection of end-organ target pathology are different, depending on whether the host or donor was treated with ATLa. Taken together, these results chart some ATLa protective effects on GvHD cellular dynamics over time and identify a previously unrecognized effect of host neutrophils in the early phase post-BMT as important determinants in the dynamics of GvHD onset and progression.-Devchand, P. R., Schmidt, B. A., Primo, V. C., Zhang, Q.-y., Arnaout, M. A., Serhan, C. N., Nikolic, B. A synthetic eicosanoid LX-mimetic unravels host-donor interactions in allogeneic BMT-induced GvHD to reveal an early protective role for host neutrophils.

Predation scars may influence host susceptibility to pathogens: evaluating the role of corallivores as vectors of coral disease.

Science.gov (United States)

Nicolet, K J; Chong-Seng, K M; Pratchett, M S; Willis, B L; Hoogenboom, M O

2018-03-27

Infectious diseases not regulated by host density, such as vector-borne diseases, have the potential to drive population declines and extinctions. Here we test the vector potential of the snail Drupella sp. and butterflyfish Chaetodon plebeius for two coral diseases, black band (BBD) and brown band (BrB) disease. Drupella transmitted BrB to healthy corals in 40% of cases immediately following feeding on infected corals, and even in 12% of cases 12 and 24 hours following feeding. However, Drupella was unable to transmit BBD in either transmission treatment. In a field experiment testing the vector potential of naturally-occurring fish assemblages, equivalent numbers of caged and uncaged coral fragments became infected with either BrB, BBD or skeletal eroding band, indicating that corallivorous fish were unlikely to have caused transmission. In aquaria, C. plebeius did not transmit either BBD or BrB, even following extended feeding on both infected and healthy nubbins. A literature review confirmed only four known coral disease vectors, all invertebrates, corroborating our conclusion that polyp-feeding fishes are unlikely to be vectors of coral diseases. This potentially because polyp-feeding fishes produce shallow lesions, not allowing pathogens to invade coral tissues. In contrast, corallivorous invertebrates that create deeper feeding scars increase pathogens transmission.

Mechanisms of host seeking by parasitic nematodes.

Science.gov (United States)

Gang, Spencer S; Hallem, Elissa A

2016-07-01

The phylum Nematoda comprises a diverse group of roundworms that includes parasites of vertebrates, invertebrates, and plants. Human-parasitic nematodes infect more than one billion people worldwide and cause some of the most common neglected tropical diseases, particularly in low-resource countries [1]. Parasitic nematodes of livestock and crops result in billions of dollars in losses each year [1]. Many nematode infections are treatable with low-cost anthelmintic drugs, but repeated infections are common in endemic areas and drug resistance is a growing concern with increasing therapeutic and agricultural administration [1]. Many parasitic nematodes have an environmental infective larval stage that engages in host seeking, a process whereby the infective larvae use sensory cues to search for hosts. Host seeking is a complex behavior that involves multiple sensory modalities, including olfaction, gustation, thermosensation, and humidity sensation. As the initial step of the parasite-host interaction, host seeking could be a powerful target for preventative intervention. However, host-seeking behavior remains poorly understood. Here we review what is currently known about the host-seeking behaviors of different parasitic nematodes, including insect-parasitic nematodes, mammalian-parasitic nematodes, and plant-parasitic nematodes. We also discuss the neural bases of these behaviors. Copyright © 2016 Elsevier B.V. All rights reserved.

Host modulation therapeutics in periodontics: role as an adjunctive periodontal therapy.

Science.gov (United States)

Shinwari, Muhammad Saad; Tanwir, Farzeen; Hyder, Pakiza Raza; Bin Saeed, Muhammad Humza

2014-09-01

Host Modulation Therapy (HMT) is a treatment concept that reduces tissue destruction and stabilizes or even regenerates inflammatory tissue by modifying host response factors. It has been used for treating osteoporosis and arthritis for several decades. However, its use in dentistry has only been recently reported. The objective of this article is to present a review of the various literatures available on HMT and also its role as adjunct therapy in periodontics. For identifying studies for this review, a PUBMED search was carried out in 2013 for all articles published till December 2012. The search was restricted to English language publications only. Longitudinal prospective and retrospective studies were included in the search. The key words used were: Host Modulation Therapy; Sub antimicrobial dose doxycycline and Non-Surgical Periodontal Therapy. The main outcomes sought were host modulation therapeutics in periodontics. Exclusion criteria included cross sectional studies, short case series as well as studies with short follow-up periods. There is a paucity of literature on HMT in periodontics although the only drug approved by United States Food and Drug Administration (FDA) is a subantimicrobial dose of doxycycline (SDD) with highly predictable results as a host modulating agent in periodontal diseases and also an effective adjunctive therapy in various diseases of periodontium. However, more randomized controlled trials are needed to obtain clinical guidelines on the usage of other host modulating agents as adjunct as well as definite therapy for periodontal diseases. SDD is an effective adjunct therapy when used in dosage of 20mg twice daily for minimum 3 months duration in various periodontal diseases with predictable clinical outcomes. It is also recommended that future clinical research on anti cytokine drugs, chemically modified tetracycline and other HMT agents should be conducted so that new drugs are available with highly predictable results.

Scaling up complexity in host-pathogens interaction models. Comment on "Coupled disease-behavior dynamics on complex networks: A review" by Z. Wang et al.

Science.gov (United States)

Aguiar, Maíra

2015-12-01

Caused by micro-organisms that are pathogenic to the host, infectious diseases have caused debilitation and premature death to large portions of the human population, leading to serious social-economic concerns. The persistence and increase in the occurrence of infectious diseases as well the emergence or resurgence of vector-borne diseases are closely related with demographic factors such as the uncontrolled urbanization and remarkable population growth, political, social and economical changes, deforestation, development of resistance to insecticides and drugs and increased human travel. In recent years, mathematical modeling became an important tool for the understanding of infectious disease epidemiology and dynamics, addressing ideas about the components of host-pathogen interactions. Acting as a possible tool to understand, predict the spread of infectious diseases these models are also used to evaluate the introduction of intervention strategies like vector control and vaccination. Many scientific papers have been published recently on these topics, and most of the models developed try to incorporate factors focusing on several different aspects of the disease (and eventually biological aspects of the vector), which can imply rich dynamic behavior even in the most basic dynamical models. As one example to be cited, there is a minimalistic dengue model that has shown rich dynamic structures, with bifurcations (Hopf, pitchfork, torus and tangent bifurcations) up to chaotic attractors in unexpected parameter regions [1,2], which was able to describe the large fluctuations observed in empirical outbreak data [3,4].

Therapeutic effects of hydrogen on chronic graft-versus-host disease.

Science.gov (United States)

Qian, Liren; Liu, Xiaopeng; Shen, Jianliang; Zhao, Defeng; Yin, Wenjie

2017-10-01

The incidence of chronic graft-versus-host disease (cGVHD) is rising recent years, which has been the leading cause of non-transplantation mortality post allogenetic hematopoietic stem cell transplantation (HSCT). Imbalance of inflammatory cytokines and fibrosis plays critical roles in the pathogenesis of cGVHD. Recent studies showed that molecular hydrogen has anti-inflammatory, antioxidant, anti-fibrosis effects. Therefore, we hypothesized that molecular hydrogen may have therapeutic effects on cGVHD. To determine whether hydrogen could protect mice from cGVHD in an MHC-incompatible murine bone marrow transplantation (BMT) model, survival rates of mice were calculated, and skin lesions were also evaluated after BMT. This article demonstrated that administration of hydrogen-rich saline increased survival rate of cGVHD mice. Administration of hydrogen-rich saline after transplantation also reduced skin lesions of cGVHD mice. Previously, we reported the therapeutic effects of hydrogen on acute GVHD. However, there was no report on the therapeutic effects of hydrogen on cGVHD mice. It is suggested that hydrogen has a potential as an effective and safe therapeutic agent on cGVHD. This study will provide new ideas on the treatment of cGVHD and has important theoretical values. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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.

Emulating Host-Microbiome Ecosystem of Human Gastrointestinal Tract in Vitro.

Science.gov (United States)

Park, Gun-Seok; Park, Min Hee; Shin, Woojung; Zhao, Connie; Sheikh, Sameer; Oh, So Jung; Kim, Hyun Jung

2017-06-01

The human gut microbiome performs prodigious physiological functions such as production of microbial metabolites, modulation of nutrient digestion and drug metabolism, control of immune system, and prevention of infection. Paradoxically, gut microbiome can also negatively orchestrate the host responses in diseases or chronic disorders, suggesting that the regulated and balanced host-gut microbiome crosstalk is a salient prerequisite in gastrointestinal physiology. To understand the pathophysiological role of host-microbiome crosstalk, it is critical to recreate in vivo relevant models of the host-gut microbiome ecosystem in human. However, controlling the multi-species microbial communities and their uncontrolled growth has remained a notable technical challenge. Furthermore, conventional two-dimensional (2D) or 3D culture systems do not recapitulate multicellular microarchitectures, mechanical dynamics, and tissue-specific functions. Here, we review recent advances and current pitfalls of in vitro and ex vivo models that display human GI functions. We also discuss how the disruptive technologies such as 3D organoids or a human organ-on-a-chip microphysiological system can contribute to better emulate host-gut microbiome crosstalks in health and disease. Finally, the medical and pharmaceutical significance of the gut microbiome-based personalized interventions is underlined as a future perspective.

Fungal invasion of normally non-phagocytic host cells.

Directory of Open Access Journals (Sweden)

Scott G Filler

2006-12-01

Full Text Available Many fungi that cause invasive disease invade host epithelial cells during mucosal and respiratory infection, and subsequently invade endothelial cells during hematogenous infection. Most fungi invade these normally non-phagocytic host cells by inducing their own uptake. Candida albicans hyphae interact with endothelial cells in vitro by binding to N-cadherin on the endothelial cell surface. This binding induces rearrangement of endothelial cell microfilaments, which results in the endocytosis of the organism. The capsule of Cryptococcus neoformans is composed of glucuronoxylomannan, which binds specifically to brain endothelial cells, and appears to mediate both adherence and induction of endocytosis. The mechanisms by which other fungal pathogens induce their own uptake are largely unknown. Some angioinvasive fungi, such as Aspergillus species and the Zygomycetes, invade endothelial cells from the abluminal surface during the initiation of invasive disease, and subsequently invade the luminal surface of endothelial cells during hematogenous dissemination. Invasion of normally non-phagocytic host cells has different consequences, depending on the type of invading fungus. Aspergillus fumigatus blocks apoptosis of pulmonary epithelial cells, whereas Paracoccidioides brasiliensis induces apoptosis of epithelial cells. This review summarizes the mechanisms by which diverse fungal pathogens invade normally non-phagocytic host cells and discusses gaps in our knowledge that provide opportunities for future research.

Virus-host interaction in feline immunodeficiency virus (FIV) infection.

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Taniwaki, Sueli Akemi; Figueiredo, Andreza Soriano; Araujo, João Pessoa

2013-12-01

Feline immunodeficiency virus (FIV) infection has been the focus of several studies because this virus exhibits genetic and pathogenic characteristics that are similar to those of the human immunodeficiency virus (HIV). FIV causes acquired immunodeficiency syndrome (AIDS) in cats, nevertheless, a large fraction of infected cats remain asymptomatic throughout life despite of persistent chronic infection. This slow disease progression may be due to the presence of factors that are involved in the natural resistance to infection and the immune response that is mounted by the animals, as well as due to the adaptation of the virus to the host. Therefore, the study of virus-host interaction is essential to the understanding of the different patterns of disease course and the virus persistence in the host, and to help with the development of effective vaccines and perhaps the cure of FIV and HIV infections. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Ocular graft-versus-host disease: An often misdiagnosed etiology of dry eye syndrome].

Science.gov (United States)

Moyal, L; Adam, R; Akesbi, J; Rodallec, F T; Nordmann, J-P

2017-02-01

To report a case of severe ocular graft-versus-host disease (GVHD) after cataract surgery. Observational case report. We describe the case of a 59-year-old man with postoperative corneal ulcer on his only functional eye. His past history reported allogenic bone marrow transplant. His visual acuity (VA) was limited to hand motions. Slit lamp examination revealed diffuse conjunctival hyperemia, severe blepharitis, Meibomian dysfunction, total corneal opacification with epithelial and stromal keratitis and neovascular invasion. Because of the severe dry eye symptoms and history of allogenic hematological stem cell transplantation, ocular GVHD was diagnosed. Functional and anatomical improvement occurred rapidly with topical cyclosporine 2%, with improved VA after treatment. With any severe dry eye syndrome in the context of allogenic bone marrow transplant, ocular GVHD must be considered. For planned ocular surgery, we recommend adding cyclosporine 0.1% treatment before and after surgery to prevent severe ocular GVHD. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Dexamethasone palmitate ameliorates macrophages-rich graft-versus-host disease by inhibiting macrophage functions.

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Nishiwaki, Satoshi; Nakayama, Takayuki; Murata, Makoto; Nishida, Tetsuya; Terakura, Seitaro; Saito, Shigeki; Kato, Tomonori; Mizuno, Hiroki; Imahashi, Nobuhiko; Seto, Aika; Ozawa, Yukiyasu; Miyamura, Koichi; Ito, Masafumi; Takeshita, Kyosuke; Kato, Hidefumi; Toyokuni, Shinya; Nagao, Keisuke; Ueda, Ryuzo; Naoe, Tomoki

2014-01-01

Macrophage infiltration of skin GVHD lesions correlates directly with disease severity, but the mechanisms underlying this relationship remain unclear and GVHD with many macrophages is a therapeutic challenge. Here, we characterize the macrophages involved in GVHD and report that dexamethasone palmitate (DP), a liposteroid, can ameliorate such GVHD by inhibiting macrophage functions. We found that host-derived macrophages could exacerbate GVHD in a mouse model through expression of higher levels of pro-inflammatory TNF-α and IFN-γ, and lower levels of anti-inflammatory IL-10 than resident macrophages in mice without GVHD. DP significantly decreased the viability and migration capacity of primary mouse macrophages compared to conventional dexamethasone in vitro. DP treatment on day 7 and day 14 decreased macrophage number, and attenuated GVHD score and subsequent mortality in a murine model. This is the first study to provide evidence that therapy for GVHD should be changed on the basis of infiltrating cell type.

A generic model for a single strain mosquito-transmitted disease with memory on the host and the vector.

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Sardar, Tridip; Rana, Sourav; Bhattacharya, Sabyasachi; Al-Khaled, Kamel; Chattopadhyay, Joydev

2015-05-01

In the present investigation, three mathematical models on a common single strain mosquito-transmitted diseases are considered. The first one is based on ordinary differential equations, and other two models are based on fractional order differential equations. The proposed models are validated using published monthly dengue incidence data from two provinces of Venezuela during the period 1999-2002. We estimate several parameters of these models like the order of the fractional derivatives (in case of two fractional order systems), the biting rate of mosquito, two probabilities of infection, mosquito recruitment and mortality rates, etc., from the data. The basic reproduction number, R0, for the ODE system is estimated using the data. For two fractional order systems, an upper bound for, R0, is derived and its value is obtained using the published data. The force of infection, and the effective reproduction number, R(t), for the three models are estimated using the data. Sensitivity analysis of the mosquito memory parameter with some important responses is worked out. We use Akaike Information Criterion (AIC) to identify the best model among the three proposed models. It is observed that the model with memory in both the host, and the vector population provides a better agreement with epidemic data. Finally, we provide a control strategy for the vector-borne disease, dengue, using the memory of the host, and the vector. Copyright © 2015 Elsevier Inc. All rights reserved.

Serum Vitamin A Levels May Affect the Severity of Ocular Graft-versus-Host Disease.

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Tong, Jiefeng; Hu, Renjian; Zhao, Yingying; Xu, Yang; Zhao, Xiaoying; Jin, Xiuming

2017-01-01

Allogeneic hematopoietic stem cell transplantation (HSCT) is a well-established therapeutic option for a range of inherited and acquired hematological disorders. However, graft-versus-host disease (GVHD) remains the leading cause of non-relapse mortality in allogeneic HSCT recipients. Ocular involvement occurs in up to 80% of chronic GVHD patients. In our cases, the diagnosis of vitamin A deficiency was suspected for GVHD patients. Serum vitamin A measurements were conducted to confirm clinical suspicions. Our study revealed significant decrease in serum levels of vitamin A in chronic liver GVHD patients. Although there have been many studies evaluating ocular manifestations in patients with GVHD, the present study is, to our knowledge, the first to study the relationship between vitamin A and ocular manifestations of GVHD in humans. Our data suggest that vitamin A deficiency affects the severity of ocular GVHD in adults.

Implicating roles of animal reservoir hosts in the resurgence of ...

African Journals Online (AJOL)

Gambian trypanosomosis (Sleeping Sickness) is a complex and debilitating disease of man. For many years the disease has been ravaging in several parts of sub-saharan Africa despite decades of therapeutic control. Although animal reservoir hosts are believed to be associated with the disease, not much evidences have ...

Impact of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia

DEFF Research Database (Denmark)

Baron, F; Labopin, M; Niederwieser, D

2012-01-01

This report investigated the impact of graft-versus-host disease (GVHD) on transplantation outcomes in 1859 acute myeloid leukemia patients given allogeneic peripheral blood stem cells after reduced-intensity conditioning (RIC allo-SCT). Grade I acute GVHD was associated with a lower risk...... of relapse (hazards ratio (HR)=0.7, P=0.02) translating into a trend for better overall survival (OS; HR=1.3; P=0.07). Grade II acute GVHD had no net impact on OS, while grade III-IV acute GVHD was associated with a worse OS (HR=0.4, P...

Clinical laboratory markers of inflammation as determinants of chronic graft-versus-host disease activity and NIH global severity.

Science.gov (United States)

Grkovic, L; Baird, K; Steinberg, S M; Williams, K M; Pulanic, D; Cowen, E W; Mitchell, S A; Hakim, F T; Martires, K J; Avila, D N; Taylor, T N; Salit, R B; Rowley, S D; Zhang, D; Fowler, D H; Bishop, M R; Gress, R E; Pavletic, S Z

2012-04-01

Chronic graft-versus-host disease (cGVHD) remains a major cause of non-relapse morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Currently there are no accepted measures of cGVHD activity to aid in clinical management and disease staging. We analyzed clinical markers of inflammation in the sera of patients with established cGVHD and correlated those with definitions of disease activity. In all, 189 adults with cGVHD (33% moderate and 66% severe according to National Institutes of Health (NIH) global scoring) were consecutively enrolled onto a cross-sectional prospective cGVHD natural history study. At the time of evaluation, 80% were receiving systemic immunosuppression and failed a median of four prior systemic therapies (PST) for their cGVHD. Lower albumin (P<0.0001), higher C-reactive protein (P = 0.043), higher platelets (P = 0.030) and higher number of PST (P<0.0001) were associated with active disease defined as clinician's intention to intensify or alter systemic therapy due to the lack of response. Higher platelet count (P = 0.021) and higher number of PST (P<0.0001) were associated with more severe diseased defined by NIH global score. This study identified common laboratory indicators of inflammation that can serve as markers of cGVHD activity and severity.

Clinical implications of oral candidiasis: host tissue damage and disseminated bacterial disease.

Science.gov (United States)

Kong, Eric F; Kucharíková, Sona; Van Dijck, Patrick; Peters, Brian M; Shirtliff, Mark E; Jabra-Rizk, Mary Ann

2015-02-01

The clinical significance of polymicrobial interactions, particularly those between commensal species with high pathogenic potential, remains largely understudied. Although the dimorphic fungal species Candida albicans and the bacterium Staphylococcus aureus are common cocolonizers of humans, they are considered leading opportunistic pathogens. Oral candidiasis specifically, characterized by hyphal invasion of oral mucosal tissue, is the most common opportunistic infection in HIV(+) and immunocompromised individuals. In this study, building on our previous findings, a mouse model was developed to investigate whether the onset of oral candidiasis predisposes the host to secondary staphylococcal infection. The findings demonstrated that in mice with oral candidiasis, subsequent exposure to S. aureus resulted in systemic bacterial infection with high morbidity and mortality. Histopathology and scanning electron microscopy of tongue tissue from moribund animals revealed massive C. albicans hyphal invasion coupled with S. aureus deep tissue infiltration. The crucial role of hyphae in the process was demonstrated using a non-hypha-producing and a noninvasive hypha-producing mutant strains of C. albicans. Further, in contrast to previous findings, S. aureus dissemination was aided but not contingent upon the presence of the Als3p hypha-specific adhesion. Importantly, impeding development of mucosal C. albicans infection by administering antifungal fluconazole therapy protected the animals from systemic bacterial disease. The combined findings from this study demonstrate that oral candidiasis may constitute a risk factor for disseminated bacterial disease warranting awareness in terms of therapeutic management of immunocompromised individuals. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Lumbricidae as transitory hosts in Metastrongylus infection in swine

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Pavlović Ivan

2005-01-01

Full Text Available Metastrongylidosis or lungworm disease in swine is a disease caused by several types of nematodes of the genus Metastrongylus. Metastrongylidae are biohelminths whose causes use transitory hosts for their development and maintaining their biological cycle, and in this case they are numerous species of Lumbricidae (earthworms. Depending on the geographic environment, numerous representatives of Lumbricidae persist as transitory hosts. In our environment, these are dominant earthworm species of the genus Eisenia spp, Dandreobena spp, Allopbophora spp, Lubricus spp, Octoiasium spp, Bimastus spp, and rarely those from the genus Heledrillus spp. Swine are infected perorally with Metastrongylidae when they ingest infected earthworms.

Vulvar and vaginal graft versus host disease: A healthcare clinic initiative

Directory of Open Access Journals (Sweden)

Naomi Van Dam

2017-01-01

Full Text Available Objective: In patients receiving bone marrow transplantation (BMT, their mucosa becomes altered and sclerotic changes in the female external genital organs occur. Although a few studies have specifically addressed vulvar and vaginal graft versus host disease (VVGvHD and its repercussions on the sexual health and quality of life of patients, VVGvHD can be overlooked by health practitioners. The objective of the study is to describe the initiation of a health care clinic specializing in VVGvHD in a general tertiary hospital. Methods: A VVGvHD clinic was founded as a part of BMT daycare in a joint initiative of the nursing staff and the medical director of the department and a gynecologist specializing in vulva and vaginal disease. Patients were assessed for vulvovaginal symptoms, such as dryness, burning, itching, pain to touch, pain during intercourse, and dysuria. These patients might be subsequently referred to the VVGvHD clinic according to their needs assessed by daycare nurses. Treatment guidelines were developed by the specialist gynecologist. Results: A total of 81 women aged 2–66 years (median age = 38 years visited the clinic from 2009 to 2015. Of these women, 70 received an allogeneic transplant and 11 underwent autologous transplantation before consultation in our clinic. VVGvHD was detected in 54% of the patients. Conclusions: The VVGvHD clinic was developed to fulfill the specific needs of female patients who underwent BMT. The pioneer clinic was founded as a joint effort of the multidisciplinary team. Evidence supporting the optimum treatment for this condition is insufficient. This was the main reason for performing this study to explore the clinic that was newly based in Israel. VVGvHD may be a fluctuating condition with frequent deterioration and improvement. Therefore, regular clinical examinations are necessary.

Differential Colonization Dynamics of Cucurbit Hosts by Erwinia tracheiphila.

Science.gov (United States)

Vrisman, Cláudio M; Deblais, Loïc; Rajashekara, Gireesh; Miller, Sally A

2016-07-01

Bacterial wilt is one of the most destructive diseases of cucurbits in the Midwestern and Northeastern United States. Although the disease has been studied since 1900, host colonization dynamics remain unclear. Cucumis- and Cucurbita-derived strains exhibit host preference for the cucurbit genus from which they were isolated. We constructed a bioluminescent strain of Erwinia tracheiphila (TedCu10-BL#9) and colonization of different cucurbit hosts was monitored. At the second-true-leaf stage, Cucumis melo plants were inoculated with TedCu10-BL#9 via wounded leaves, stems, and roots. Daily monitoring of colonization showed bioluminescent bacteria in the inoculated leaf and petiole beginning 1 day postinoculation (DPI). The bacteria spread to roots via the stem by 2 DPI, reached the plant extremities 4 DPI, and the plant wilted 6 DPI. However, Cucurbita plants inoculated with TedCu10-BL#9 did not wilt, even at 35 DPI. Bioluminescent bacteria were detected 6 DPI in the main stem of squash and pumpkin plants, which harbored approximately 10(4) and 10(1) CFU/g, respectively, of TedCu10-BL#9 without symptoms. Although significantly less systemic plant colonization was observed in nonpreferred host Cucurbita plants compared with preferred hosts, the mechanism of tolerance of Cucurbita plants to E. tracheiphila strains from Cucumis remains unknown.

Mosquito-host interactions during and after an outbreak of equine viral encephalitis in Eastern Panama.

Directory of Open Access Journals (Sweden)

Wayra G Navia-Gine

Full Text Available Mosquito blood meals provide information about the feeding habits and host preference of potential arthropod-borne disease vectors. Although mosquito-borne diseases are ubiquitous in the Neotropics, few studies in this region have assessed patterns of mosquito-host interactions, especially during actual disease outbreaks. Based on collections made during and after an outbreak of equine viral encephalitis, we identified the source of 338 blood meals from 10 species of mosquitoes from Aruza Abajo, a location in Darien province in eastern Panama. A PCR based method targeting three distinct mitochondrial targets and subsequent DNA sequencing was used in an effort to delineate vector-host relationships. At Aruza Abajo, large domesticated mammals dominated the assemblage of mosquito blood meals while wild bird and mammal species represented only a small portion of the blood meal pool. Most mosquito species fed on a variety of hosts; foraging index analysis indicates that eight of nine mosquito species utilize hosts at similar proportions while a stochastic model suggests dietary overlap among species was greater than would be expected by chance. The results from our null-model analysis of mosquito diet overlap are consistent with the hypothesis that in landscapes where large domestic animals dominate the local biomass, many mosquito species show little host specificity, and feed upon hosts in proportion to their biomass, which may have implications for the role of livestocking patterns in vector-borne disease ecology.

Bartonella entry mechanisms into mammalian host cells.

Science.gov (United States)

Eicher, Simone C; Dehio, Christoph

2012-08-01

The Gram-negative genus Bartonella comprises arthropod-borne pathogens that typically infect mammals in a host-specific manner. Bartonella bacilliformis and Bartonella quintana are human-specific pathogens, while several zoonotic bartonellae specific for diverse animal hosts infect humans as an incidental host. Clinical manifestations of Bartonella infections range from mild symptoms to life-threatening disease. Following transmission by blood-sucking arthropods or traumatic contact with infected animals, bartonellae display sequential tropisms towards endothelial and possibly other nucleated cells and erythrocytes, the latter in a host-specific manner. Attachment to the extracellular matrix (ECM) and to nucleated cells is mediated by surface-exposed bacterial adhesins, in particular trimeric autotransporter adhesins (TAAs). The subsequent engulfment of the pathogen into a vacuolar structure follows a unique series of events whereby the pathogen avoids the endolysosomal compartments. For Bartonella henselae and assumingly most other species, the infection process is aided at different steps by Bartonella effector proteins (Beps). They are injected into host cells through the type IV secretion system (T4SS) VirB/D4 and subvert host cellular functions to favour pathogen uptake. Bacterial binding to erythrocytes is mediated by Trw, another T4SS, in a strictly host-specific manner, followed by pathogen-forced uptake involving the IalB invasin and subsequent replication and persistence within a membrane-bound intra-erythrocytic compartment. © 2012 Blackwell Publishing Ltd.

Host nutrition alters the variance in parasite transmission potential.

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Vale, Pedro F; Choisy, Marc; Little, Tom J

2013-04-23

The environmental conditions experienced by hosts are known to affect their mean parasite transmission potential. How different conditions may affect the variance of transmission potential has received less attention, but is an important question for disease management, especially if specific ecological contexts are more likely to foster a few extremely infectious hosts. Using the obligate-killing bacterium Pasteuria ramosa and its crustacean host Daphnia magna, we analysed how host nutrition affected the variance of individual parasite loads, and, therefore, transmission potential. Under low food, individual parasite loads showed similar mean and variance, following a Poisson distribution. By contrast, among well-nourished hosts, parasite loads were right-skewed and overdispersed, following a negative binomial distribution. Abundant food may, therefore, yield individuals causing potentially more transmission than the population average. Measuring both the mean and variance of individual parasite loads in controlled experimental infections may offer a useful way of revealing risk factors for potential highly infectious hosts.

Human borna disease virus infection impacts host proteome and histone lysine acetylation in human oligodendroglia cells

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Liu, Xia [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Department of Neurology, The Fifth People' s Hospital of Shanghai, School of Medicine, Fudan University, Shanghai, 200240 (China); Zhao, Libo [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Department of Neurology, The Third People' s Hospital of Chongqing, 400014 (China); Yang, Yongtao [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, 400016 (China); Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016 (China); Bode, Liv [Bornavirus Research Group affiliated to the Free University of Berlin, Berlin (Germany); Huang, Hua [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, 400016 (China); Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016 (China); Liu, Chengyu [Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, 400016 (China); Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016 (China); Huang, Rongzhong [Department of Rehabilitative Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010 (China); Zhang, Liang [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, 400016 (China); Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016 (China); and others

2014-09-15

Background: Borna disease virus (BDV) replicates in the nucleus and establishes persistent infections in mammalian hosts. A human BDV strain was used to address the first time, how BDV infection impacts the proteome and histone lysine acetylation (Kac) of human oligodendroglial (OL) cells, thus allowing a better understanding of infection-driven pathophysiology in vitro. Methods: Proteome and histone lysine acetylation were profiled through stable isotope labeling for cell culture (SILAC)-based quantitative proteomics. The quantifiable proteome was annotated using bioinformatics. Histone acetylation changes were validated by biochemistry assays. Results: Post BDV infection, 4383 quantifiable differential proteins were identified and functionally annotated to metabolism pathways, immune response, DNA replication, DNA repair, and transcriptional regulation. Sixteen of the thirty identified Kac sites in core histones presented altered acetylation levels post infection. Conclusions: BDV infection using a human strain impacted the whole proteome and histone lysine acetylation in OL cells. - Highlights: • A human strain of BDV (BDV Hu-H1) was used to infect human oligodendroglial cells (OL cells). • This study is the first to reveal the host proteomic and histone Kac profiles in BDV-infected OL cells. • BDV infection affected the expression of many transcription factors and several HATs and HDACs.

Sporadic Creutzfeldt-Jakob Disease: Prion Pathology in Medulla Oblongata-Possible Routes of Infection and Host Susceptibility.

Science.gov (United States)

Iacono, Diego; Ferrari, Sergio; Gelati, Matteo; Zanusso, Gianluigi; Mariotto, Sara; Monaco, Salvatore

2015-01-01

Sporadic Creutzfeldt-Jakob disease (sCJD), the most frequent human prion disorder, is characterized by remarkable phenotypic variability, which is influenced by the conformation of the pathologic prion protein and the methionine/valine polymorphic codon 129 of the prion protein gene. While the etiology of sCJD remains unknown, it has been hypothesized that environmental exposure to prions might occur through conjunctival/mucosal contact, oral ingestion, inhalation, or simultaneous involvement of the olfactory and enteric systems. We studied 21 subjects with definite sCJD to assess neuropathological involvement of the dorsal motor nucleus of the vagus and other medullary nuclei and to evaluate possible associations with codon 129 genotype and prion protein conformation. The present data show that prion protein deposition was detected in medullary nuclei of distinct sCJD subtypes, either valine homozygous or heterozygous at codon 129. These findings suggest that an "environmental exposure" might occur, supporting the hypothesis that external sources of contamination could contribute to sCJD in susceptible hosts. Furthermore, these novel data could shed the light on possible causes of sCJD through a "triple match" hypothesis that identify environmental exposure, host genotype, and direct exposure of specific anatomical regions as possible pathogenetic factors.

Human borna disease virus infection impacts host proteome and histone lysine acetylation in human oligodendroglia cells

International Nuclear Information System (INIS)

Liu, Xia; Zhao, Libo; Yang, Yongtao; Bode, Liv; Huang, Hua; Liu, Chengyu; Huang, Rongzhong; Zhang, Liang

2014-01-01

Background: Borna disease virus (BDV) replicates in the nucleus and establishes persistent infections in mammalian hosts. A human BDV strain was used to address the first time, how BDV infection impacts the proteome and histone lysine acetylation (Kac) of human oligodendroglial (OL) cells, thus allowing a better understanding of infection-driven pathophysiology in vitro. Methods: Proteome and histone lysine acetylation were profiled through stable isotope labeling for cell culture (SILAC)-based quantitative proteomics. The quantifiable proteome was annotated using bioinformatics. Histone acetylation changes were validated by biochemistry assays. Results: Post BDV infection, 4383 quantifiable differential proteins were identified and functionally annotated to metabolism pathways, immune response, DNA replication, DNA repair, and transcriptional regulation. Sixteen of the thirty identified Kac sites in core histones presented altered acetylation levels post infection. Conclusions: BDV infection using a human strain impacted the whole proteome and histone lysine acetylation in OL cells. - Highlights: • A human strain of BDV (BDV Hu-H1) was used to infect human oligodendroglial cells (OL cells). • This study is the first to reveal the host proteomic and histone Kac profiles in BDV-infected OL cells. • BDV infection affected the expression of many transcription factors and several HATs and HDACs

The prevalence and prognostic value of concomitant eosinophilia in chronic graft-versus-host disease after allogeneic stem cell transplantation

DEFF Research Database (Denmark)

Mortensen, Katrine Brandt; Gerds, Thomas Alexander; Bjerrum, Ole Weis

2014-01-01

The prognostic significance of eosinophilia after myeloablative allogeneic stem cell transplantation (ASCT) remains to be established. Patients, whom developed chronic graft-versus-host disease (cGVHD) after ASCT, were included (n = 142). Eosinophil count was analyzed at cGVHD onset. We observed...... no significant association between EO and the grade of cGVHD, thrombocytopenia, nor extensive skin involvement. Importantly, we observed no significant association between cGVHD with concomitant eosinophilia and long-term clinical outcomes, and subgroup analyses revealed a considerable confounding effect...

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

The Green Tea Catechin Epigallocatechin Gallate Ameliorates Graft-versus-Host Disease.

Directory of Open Access Journals (Sweden)

Sabine Westphal

Full Text Available Allogeneic hematopoetic stem cell transplantation (allo-HSCT is a standard treatment for leukemia and other hematologic malignancies. The major complication of allo-HSCT is graft-versus-host-disease (GVHD, a progressive inflammatory illness characterized by donor immune cells attacking the organs of the recipient. Current GVHD prevention and treatment strategies use immune suppressive drugs and/or anti-T cell reagents these can lead to increased risk of infections and tumor relapse. Recent research demonstrated that epigallocatechin gallate (EGCG, a component found in green tea leaves at a level of 25-35% at dry weight, may be useful in the inhibition of GVHD due to its immune modulatory, anti-oxidative and anti-angiogenic capacities. In murine allo-HSCT recipients treated with EGCG, we found significantly reduced GVHD scores, reduced target organ GVHD and improved survival. EGCG treated allo-HSCT recipients had significantly higher numbers of regulatory T cells in GVHD target organs and in the blood. Furthermore, EGCG treatment resulted in diminished oxidative stress indicated by significant changes of glutathione blood levels as well as glutathione peroxidase in the colon. In summary, our study provides novel evidence demonstrating that EGCG ameliorates lethal GVHD and reduces GVHD-related target organ damage. Possible mechanisms are increased regulatory T cell numbers and reduced oxidative stress.

Preventing transfusion-associated graft-versus-host disease: state of the art

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Fast LD

2015-01-01

Full Text Available Loren D Fast Division of Hematology/Oncology, Rhode Island Hospital and Warren Alpert School of Medicine at Brown University, Providence, RI, USA Abstract: The transfer of pathogens and the induction of immune responses are deleterious consequences that can result from the transfusion of blood products. Transfusion-associated graft-versus-host disease (TA-GVHD, the most severe immune consequence, occurs when recipient immune responses are incapable of effectively eliminating donor leukocytes, permitting unabated responses of the donor T lymphocytes. Currently, prevention of TA-GVHD is routinely accomplished by exposing blood products to γ-irradiation in order to prevent donor T cell proliferation. Alternative protocols are being developed to meet the challenges associated with the use of γ-irradiation. Use of pathogen reduction protocols, which interfere with nucleic acid replication by modifying nucleic acids, are increasing. Comparison of pathogen reduction protocols with γ-irradiation have found that both protocols are equally effective in preventing T lymphocyte proliferation and GVHD responses when testing in both in vitro and in vivo models. The potential use of pathogen reduction protocols to treat whole blood prior to separation into its components could provide a cost-effective method for preventing TA-GVHD in the future. Keywords: blood transfusion, GVHD, pathogen reduction, irradiation

The Bcl-2 Family in Host-Virus Interactions.

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Kvansakul, Marc; Caria, Sofia; Hinds, Mark G

2017-10-06

Members of the B cell lymphoma-2 (Bcl-2) family are pivotal arbiters of mitochondrially mediated apoptosis, a process of fundamental importance during tissue development, homeostasis, and disease. At the structural and mechanistic level, the mammalian members of the Bcl-2 family are increasingly well understood, with their interplay ultimately deciding the fate of a cell. Dysregulation of Bcl-2-mediated apoptosis underlies a plethora of diseases, and numerous viruses have acquired homologs of Bcl-2 to subvert host cell apoptosis and autophagy to prevent premature death of an infected cell. Here we review the structural biology, interactions, and mechanisms of action of virus-encoded Bcl-2 proteins, and how they impact on host-virus interactions to ultimately enable successful establishment and propagation of viral infections.

Responses of a bacterial pathogen to phosphorus limitation of its aquatic invertebrate host

OpenAIRE

Frost, P. C.; Ebert, D.; Smith, V. H.

2008-01-01

Host nutrition is thought to affect the establishment, persistence, and severity of pathogenic infections. Nutrient-deficient foods possibly benefit pathogens by constraining host immune function or benefit hosts by limiting parasite growth and reproduction. However, the effects of poor elemental food quality on a host's susceptibility to infection and disease have received little study. Here we show that the bacterial microparasite Pasteuria ramosa is affected by the elemental nutrition of i...

The ecology, evolution, impacts and management of host-parasite interactions of marine molluscs.

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Coen, Loren D; Bishop, Melanie J

2015-10-01

Molluscs are economically and ecologically important components of aquatic ecosystems. In addition to supporting valuable aquaculture and wild-harvest industries, their populations determine the structure of benthic communities, cycling of nutrients, serve as prey resources for higher trophic levels and, in some instances, stabilize shorelines and maintain water quality. This paper reviews existing knowledge of the ecology of host-parasite interactions involving marine molluscs, with a focus on gastropods and bivalves. It considers the ecological and evolutionary impacts of molluscan parasites on their hosts and vice versa, and on the communities and ecosystems in which they are a part, as well as disease management and its ecological impacts. An increasing number of case studies show that disease can have important effects on marine molluscs, their ecological interactions and ecosystem services, at spatial scales from centimeters to thousands of kilometers and timescales ranging from hours to years. In some instances the cascading indirect effects arising from parasitic infection of molluscs extend well beyond the temporal and spatial scales at which molluscs are affected by disease. In addition to the direct effects of molluscan disease, there can be large indirect impacts on marine environments resulting from strategies, such as introduction of non-native species and selective breeding for disease resistance, put in place to manage disease. Much of our understanding of impacts of molluscan diseases on the marine environment has been derived from just a handful of intensively studied marine parasite-host systems, namely gastropod-trematode, cockle-trematode, and oyster-protistan interactions. Understanding molluscan host-parasite dynamics is of growing importance because: (1) expanding aquaculture; (2) current and future climate change; (3) movement of non-native species; and (4) coastal development are modifying molluscan disease dynamics, ultimately leading to

Sympatric diversification vs. immigration: deciphering host-plant specialization in a polyphagous insect, the stolbur phytoplasma vector Hyalesthes obsoletus (Cixiidae).

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Imo, Miriam; Maixner, Michael; Johannesen, Jes

2013-04-01

The epidemiology of vector transmitted plant diseases is highly influenced by dispersal and the host-plant range of the vector. Widening the vector's host range may increase transmission potential, whereas specialization may induce specific disease cycles. The process leading to a vector's host shift and its epidemiological outcome is therefore embedded in the frameworks of sympatric evolution vs. immigration of preadapted populations. In this study, we analyse whether a host shift of the stolbur phytoplasma vector, Hyalesthes obsoletus from field bindweed to stinging nettle in its northern distribution range evolved sympatrically or by immigration. The exploitation of stinging nettle has led to outbreaks of the grapevine disease bois noir caused by a stinging nettle-specific phytoplasma strain. Microsatellite data from populations from northern and ancestral ranges provide strong evidence for sympatric host-race evolution in the northern range: Host-plant associated populations were significantly differentiated among syntopic sites (0.054 nettle-specific phytoplasma strain by plant-unspecific vectors. The evolution of host races in the northern range has led to specific vector-based bois noir disease cycles. © 2013 Blackwell Publishing Ltd.

Host and Symbiont Jointly Control Gut Microbiota during Complete Metamorphosis

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Johnston, Paul R.; Rolff, Jens

2015-01-01

Holometabolous insects undergo a radical anatomical re-organisation during metamorphosis. This poses a developmental challenge: the host must replace the larval gut but at the same time retain symbiotic gut microbes and avoid infection by opportunistic pathogens. By manipulating host immunity and bacterial competitive ability, we study how the host Galleria mellonella and the symbiotic bacterium Enterococcus mundtii interact to manage the composition of the microbiota during metamorphosis. Disenabling one or both symbiotic partners alters the composition of the gut microbiota, which incurs fitness costs: adult hosts with a gut microbiota dominated by pathogens such as Serratia and Staphylococcus die early. Our results reveal an interaction that guarantees the safe passage of the symbiont through metamorphosis and benefits the resulting adult host. Host-symbiont “conspiracies” as described here are almost certainly widespread in holometobolous insects including many disease vectors. PMID:26544881

Domestic animal hosts strongly influence human-feeding rates of the Chagas disease vector Triatoma infestans in Argentina.

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Ricardo E Gürtler

Full Text Available The host species composition in a household and their relative availability affect the host-feeding choices of blood-sucking insects and parasite transmission risks. We investigated four hypotheses regarding factors that affect blood-feeding rates, proportion of human-fed bugs (human blood index, and daily human-feeding rates of Triatoma infestans, the main vector of Chagas disease.A cross-sectional survey collected triatomines in human sleeping quarters (domiciles of 49 of 270 rural houses in northwestern Argentina. We developed an improved way of estimating the human-feeding rate of domestic T. infestans populations. We fitted generalized linear mixed-effects models to a global model with six explanatory variables (chicken blood index, dog blood index, bug stage, numbers of human residents, bug abundance, and maximum temperature during the night preceding bug catch and three response variables (daily blood-feeding rate, human blood index, and daily human-feeding rate. Coefficients were estimated via multimodel inference with model averaging.Median blood-feeding intervals per late-stage bug were 4.1 days, with large variations among households. The main bloodmeal sources were humans (68%, chickens (22%, and dogs (9%. Blood-feeding rates decreased with increases in the chicken blood index. Both the human blood index and daily human-feeding rate decreased substantially with increasing proportions of chicken- or dog-fed bugs, or the presence of chickens indoors. Improved calculations estimated the mean daily human-feeding rate per late-stage bug at 0.231 (95% confidence interval, 0.157-0.305.Based on the changing availability of chickens in domiciles during spring-summer and the much larger infectivity of dogs compared with humans, we infer that the net effects of chickens in the presence of transmission-competent hosts may be more adequately described by zoopotentiation than by zooprophylaxis. Domestic animals in domiciles profoundly affect the

Small proteins of plant-pathogenic fungi secreted during host colonization.

NARCIS (Netherlands)

Rep, M.

2005-01-01

Small proteins secreted by plant pathogenic fungi in their hosts have been implicated in disease symptom development as well as in R-gene mediated disease resistance. Characteristically, this class of proteins shows very limited phylogenetic distribution, possibly due to accelerated evolution

Insects and diseases

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John W. Couston

2009-01-01

Insects and diseases are a natural part of forested ecosystems. Their activity is partially regulated by biotic factors, e.g., host abundance, host quality; physical factors, e.g., soil, climate; and disturbances (Berryman 1986). Insects and diseases can influence both forest patterns and forest processes by causing, for example, defoliation and mortality. These...

Temporal dynamics of host molecular responses differentiate symptomatic and asymptomatic influenza a infection.

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Yongsheng Huang

2011-08-01

Full Text Available Exposure to influenza viruses is necessary, but not sufficient, for healthy human hosts to develop symptomatic illness. The host response is an important determinant of disease progression. In order to delineate host molecular responses that differentiate symptomatic and asymptomatic Influenza A infection, we inoculated 17 healthy adults with live influenza (H3N2/Wisconsin and examined changes in host peripheral blood gene expression at 16 timepoints over 132 hours. Here we present distinct transcriptional dynamics of host responses unique to asymptomatic and symptomatic infections. We show that symptomatic hosts invoke, simultaneously, multiple pattern recognition receptors-mediated antiviral and inflammatory responses that may relate to virus-induced oxidative stress. In contrast, asymptomatic subjects tightly regulate these responses and exhibit elevated expression of genes that function in antioxidant responses and cell-mediated responses. We reveal an ab initio molecular signature that strongly correlates to symptomatic clinical disease and biomarkers whose expression patterns best discriminate early from late phases of infection. Our results establish a temporal pattern of host molecular responses that differentiates symptomatic from asymptomatic infections and reveals an asymptomatic host-unique non-passive response signature, suggesting novel putative molecular targets for both prognostic assessment and ameliorative therapeutic intervention in seasonal and pandemic influenza.

Radiation-induced mouse chimeras: a cellular analysis of the major lymphoid compartments, factors affecting lethal graft versus host disease and host-tumor interactions

International Nuclear Information System (INIS)

Almaraz, R.

1981-01-01

The major lymphoid compartments of allogeneic bone marrow chimeras were evaluated for the extent of cell chimerism and distribution of Thy 1 and la bearing cells. These chimeras contained lymphoid cell primarily of donor origin. The bone marrow compartment was a mixture of host and donor origin cells. The distribution of Thy 1 and la bearing cells was similar as in normal mice. The effect of adult thymectomy alone or followed by whole-body irradiation and bone marrow reconstitution on the distribution of the Thy 1 positive cells was also investigated. Thymectomy with or without WBI and bone marrow reconstitution significantly lowered the number of Thy 1 bearing cells in the blood and spleen. The number of la bearing cells did not appear to be affected by thymectomy. The role of circulating lymphoid cells in the incidence of lethal graft versus host disease (GVHD) in radiation induced fully allogeneic mouse chimeras was studied. Mice reconstituted with allogeneic bone marrow from bled donors had a statistically lower incidence of GVHD than those reconstituted with bone marrow from unbled donors. Addition of mature peripheral lymphocytes from blood to the reconstituting bone marrow cells from bled donors reduplicated the high incidence of lethal GVHD. It was demonstrated that the bone marrow of mice not exsanguinated prior to harvesting of bone marrow contained significant numbers of peripheral contaminating cells in the harvested bone marrow. The role of suppressor cell elimination in resisting tumor growth was investigated using radiation induced mouse chimeras. Local effects of irradiation alone at the site of tumor inoculation could account for this lack of growth

A murine model of graft-versus-host disease induced by allogeneic bone marrow transplantation

International Nuclear Information System (INIS)

Hu Jiangwei; Jin Jiangang; Ning Hongmei; Yu Liquan; Feng Kai; Chen Hu; Wang Lisha

2007-01-01

Objective: To establish the model of graft-versus-host disease (GVHD) in mice with allogeneic bone marrow transplantation. Methods: Bone marrow cells were combined with spleen cells of male donor C57BL/6 mice according to different proportions, then were transfused into female postradiation recipient BALB/c mice. General state, life span and histopathology of the recipient mice and detected chimera were observed. Results and Conclusion:The recipient mice groups which accepted above 5 x 10 6 donor spleen cells developed acute GVHD after different peroids of time. The GVHD model in mice after allo-BMT was successfully established. The transfusion of 5 x 10 6 -5 x 10 7 spleen cells may be adequate to establish the murine model of GVHD for the prevention and treatment of GVHD. The number of murine spleen cells can be chosen according to the experimental requirement. (authors)

Serum Vitamin A Levels May Affect the Severity of Ocular Graft-versus-Host Disease

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Jiefeng Tong

2017-06-01

Full Text Available Allogeneic hematopoietic stem cell transplantation (HSCT is a well-established therapeutic option for a range of inherited and acquired hematological disorders. However, graft-versus-host disease (GVHD remains the leading cause of non-relapse mortality in allogeneic HSCT recipients. Ocular involvement occurs in up to 80% of chronic GVHD patients. In our cases, the diagnosis of vitamin A deficiency was suspected for GVHD patients. Serum vitamin A measurements were conducted to confirm clinical suspicions. Our study revealed significant decrease in serum levels of vitamin A in chronic liver GVHD patients. Although there have been many studies evaluating ocular manifestations in patients with GVHD, the present study is, to our knowledge, the first to study the relationship between vitamin A and ocular manifestations of GVHD in humans. Our data suggest that vitamin A deficiency affects the severity of ocular GVHD in adults.

Two-host, two-vector basic reproduction ratio (R(0 for bluetongue.

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Joanne Turner

Full Text Available Mathematical formulations for the basic reproduction ratio (R(0 exist for several vector-borne diseases. Generally, these are based on models of one-host, one-vector systems or two-host, one-vector systems. For many vector borne diseases, however, two or more vector species often co-occur and, therefore, there is a need for more complex formulations. Here we derive a two-host, two-vector formulation for the R(0 of bluetongue, a vector-borne infection of ruminants that can have serious economic consequences; since 1998 for example, it has led to the deaths of well over 1 million sheep in Europe alone. We illustrate our results by considering the situation in South Africa, where there are two major hosts (sheep, cattle and two vector species with differing ecologies and competencies as vectors, for which good data exist. We investigate the effects on R(0 of differences in vector abundance, vector competence and vector host preference between vector species. Our results indicate that R(0 can be underestimated if we assume that there is only one vector transmitting the infection (when there are in fact two or more and/or vector host preferences are overlooked (unless the preferred host is less beneficial or more abundant. The two-host, one-vector formula provides a good approximation when the level of cross-infection between vector species is very small. As this approaches the level of intraspecies infection, a combination of the two-host, one-vector R(0 for each vector species becomes a better estimate. Otherwise, particularly when the level of cross-infection is high, the two-host, two-vector formula is required for accurate estimation of R(0. Our results are equally relevant to Europe, where at least two vector species, which co-occur in parts of the south, have been implicated in the recent epizootic of bluetongue.

Probing Molecular Insights into Zika Virus–Host Interactions

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Ina Lee

2018-05-01

Full Text Available The recent Zika virus (ZIKV outbreak in the Americas surprised all of us because of its rapid spread and association with neurologic disorders including fetal microcephaly, brain and ocular anomalies, and Guillain–Barré syndrome. In response to this global health crisis, unprecedented and world-wide efforts are taking place to study the ZIKV-related human diseases. Much has been learned about this virus in the areas of epidemiology, genetic diversity, protein structures, and clinical manifestations, such as consequences of ZIKV infection on fetal brain development. However, progress on understanding the molecular mechanism underlying ZIKV-associated neurologic disorders remains elusive. To date, we still lack a good understanding of; (1 what virologic factors are involved in the ZIKV-associated human diseases; (2 which ZIKV protein(s contributes to the enhanced viral pathogenicity; and (3 how do the newly adapted and pandemic ZIKV strains alter their interactions with the host cells leading to neurologic defects? The goal of this review is to explore the molecular insights into the ZIKV–host interactions with an emphasis on host cell receptor usage for viral entry, cell innate immunity to ZIKV, and the ability of ZIKV to subvert antiviral responses and to cause cytopathic effects. We hope this literature review will inspire additional molecular studies focusing on ZIKV–host Interactions.

Probing Molecular Insights into Zika Virus–Host Interactions

Science.gov (United States)

Lee, Ina; Li, Ge; Wang, Shusheng; Desprès, Philippe; Zhao, Richard Y.

2018-01-01

The recent Zika virus (ZIKV) outbreak in the Americas surprised all of us because of its rapid spread and association with neurologic disorders including fetal microcephaly, brain and ocular anomalies, and Guillain–Barré syndrome. In response to this global health crisis, unprecedented and world-wide efforts are taking place to study the ZIKV-related human diseases. Much has been learned about this virus in the areas of epidemiology, genetic diversity, protein structures, and clinical manifestations, such as consequences of ZIKV infection on fetal brain development. However, progress on understanding the molecular mechanism underlying ZIKV-associated neurologic disorders remains elusive. To date, we still lack a good understanding of; (1) what virologic factors are involved in the ZIKV-associated human diseases; (2) which ZIKV protein(s) contributes to the enhanced viral pathogenicity; and (3) how do the newly adapted and pandemic ZIKV strains alter their interactions with the host cells leading to neurologic defects? The goal of this review is to explore the molecular insights into the ZIKV–host interactions with an emphasis on host cell receptor usage for viral entry, cell innate immunity to ZIKV, and the ability of ZIKV to subvert antiviral responses and to cause cytopathic effects. We hope this literature review will inspire additional molecular studies focusing on ZIKV–host Interactions. PMID:29724036

Mycobacterium leprae–host-cell interactions and genetic determinants in leprosy: an overview

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Pinheiro, Roberta Olmo; de Souza Salles, Jorgenilce; Sarno, Euzenir Nunes; Sampaio, Elizabeth Pereira

2011-01-01

Leprosy, also known as Hansen’s disease, is a chronic infectious disease caused by Mycobacterium leprae in which susceptibility to the mycobacteria and its clinical manifestations are attributed to the host immune response. Even though leprosy prevalence has decreased dramatically, the high number of new cases indicates active transmission. Owing to its singular features, M. leprae infection is an attractive model for investigating the regulation of human immune responses to pathogen-induced disease. Leprosy is one of the most common causes of nontraumatic peripheral neuropathy worldwide. The proportion of patients with disabilities is affected by the type of leprosy and delay in diagnosis. This article briefly reviews the clinical features as well as the immunopathological mechanisms related to the establishment of the different polar forms of leprosy, the mechanisms related to M. leprae–host cell interactions and prophylaxis and diagnosis of this complex disease. Host genetic factors are summarized and the impact of the development of interventions that prevent, reverse or limit leprosy-related nerve impairments are discussed. PMID:21366421

Mammal decline, linked to invasive Burmese python, shifts host use of vector mosquito towards reservoir hosts of a zoonotic disease.

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Hoyer, Isaiah J; Blosser, Erik M; Acevedo, Carolina; Thompson, Anna Carels; Reeves, Lawrence E; Burkett-Cadena, Nathan D

2017-10-01

Invasive apex predators have profound impacts on natural communities, yet the consequences of these impacts on the transmission of zoonotic pathogens are unexplored. Collapse of large- and medium-sized mammal populations in the Florida Everglades has been linked to the invasive Burmese python, Python bivittatus Kuhl. We used historic and current data to investigate potential impacts of these community effects on contact between the reservoir hosts (certain rodents) and vectors of Everglades virus, a zoonotic mosquito-borne pathogen that circulates in southern Florida. The percentage of blood meals taken from the primary reservoir host, the hispid cotton rat, Sigmodon hispidus Say and Ord, increased dramatically (422.2%) from 1979 (14.7%) to 2016 (76.8%), while blood meals from deer, raccoons and opossums decreased by 98.2%, reflecting precipitous declines in relative abundance of these larger mammals, attributed to python predation. Overall species diversity of hosts detected in Culex cedecei blood meals from the Everglades declined by 40.2% over the same period ( H (1979) = 1.68, H (2016) = 1.01). Predictions based upon the dilution effect theory suggest that increased relative feedings upon reservoir hosts translate into increased abundance of infectious vectors, and a corresponding upsurge of Everglades virus occurrence and risk of human exposure, although this was not tested in the current study. This work constitutes the first indication that an invasive predator can increase contact between vectors and reservoirs of a human pathogen and highlights unrecognized indirect impacts of invasive predators. © 2017 The Author(s).

De novo generation of helper virus-satellite chimera RNAs results in disease attenuation and satellite sequence acquisition in a host-dependent manner.

Science.gov (United States)

Pyle, J D; Scholthof, Karen-Beth G

2018-01-15

Panicum mosaic virus (PMV) is a helper RNA virus for satellite RNAs (satRNAs) and a satellite virus (SPMV). Here, we describe modifications that occur at the 3'-end of a satRNA of PMV, satS. Co-infections of PMV+satS result in attenuation of the disease symptoms induced by PMV alone in Brachypodium distachyon and proso millet. The 375 nt satS acquires ~100-200 nts from the 3'-end of PMV during infection and is associated with decreased abundance of the PMV RNA and capsid protein in millet. PMV-satS chimera RNAs were isolated from native infections of St. Augustinegrass and switchgrass. Phylogenetic analyses revealed that the chimeric RNAs clustered according to the host species from which they were isolated. Additionally, the chimera satRNAs acquired non-viral "linker" sequences in a host-specific manner. These results highlight the dynamic regulation of viral pathogenicity by satellites, and the selective host-dependent, sequence-based pressures for driving satRNA generation and genome compositions. Copyright © 2017 Elsevier Inc. All rights reserved.

Autologous Graft versus Host Disease: An Emerging Complication in Patients with Multiple Myeloma

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Anu Batra

2014-01-01

Full Text Available Autologous graft versus host disease (autoGVHD is a rare transplant complication with significant morbidity and mortality. It has been hypothesized that patients with multiple myeloma might be predisposed to autoGVHD through dysregulation of the immune response resulting from either their disease, the immunomodulatory agents (IMiDs used to treat it, or transplant conditioning regimen. Hematopoietic progenitor cell (HPC products were available from 8 multiple myeloma patients with biopsy-proven autoGVHD, 16 matched multiple myeloma patients who did not develop autoGVHD, and 7 healthy research donors. The data on number of transplants prior to developing autoGVHD, mobilization regimens, exposure to proteasome inhibitors, use of IMiDs, and class I human leukocyte antigen types (HLA A and B were collected. The HPC products were analyzed by flow cytometry for expression of CD3, CD4, CD8, CD25, CD56, and FoxP3. CD3+ cell number was significantly lower in autoGVHD patients compared to unaffected controls (P=0.047. On subset analysis of CD3+ cells, CD8+ cells (but not CD4+ cells were found to be significantly lower in patients with autoGVHD (P=0.038. HLA-B55 expression was significantly associated with development of autoGVHD (P=0.032. Lower percentages of CD3+ and CD8+ T-cells and HLA-B55 expression may be predisposing factors for developing autoGVHD in myeloma.

MR findings in patients with disabling musculocutaneous chronic graft-versus-host disease

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Horger, M.; Boss, A.; Claussen, C.D. [Eberhard-Karls-University, Department of Diagnostic Radiology, Tuebingen (Germany); Bethge, W.; Faul, C.; Vogel, W. [Eberhard-Karls-University, Department of Internal Medicine-Oncology, Tuebingen (Germany); Fierlbeck, G. [Eberhard-Karls-University, Department of Dermatology, Tuebingen (Germany); Bornemann, A. [Eberhard-Karls-University, Insitute for Brain Research, Tuebingen (Germany)

2008-10-15

To describe musculocutaneous MR-findings responsible for disability in chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic cell transplantation (HCT). Between June 2005 and February 2008, we performed whole-body musculoskeletal magnetic resonance imaging (MRI; n = 12) or regional MRI (n = 4) in 16 consecutive patients presenting with disabling sclerodermatous cGVHD (e.g., skin edema, fixed deep dermal sclerosis, joint contractures, painful muscular contractures, or myalgia). In all patients, MRI showed musculocutaneous abnormalities reflecting different degrees of inflammation and collagen tissue involvement of the skin (n = 10), subcutaneous fat tissue (n = 13), muscle fasciae (n = 16), subfascial muscular septae (n = 6), or findings compatible with myositis (n = 3). The most frequently involved muscle fasciae comprised those of the vastus lateralis muscle (n = 12), biceps femoris muscle (n = 11), gastrocnemius medialis muscle (n = 8), serratus anterior muscle, and latissimus dorsi muscle (each, n = 5). Increased signal of involved tissues on STIR-images and fat-saturated postgadolinium T1-weighted images represented the most frequent MR-signal abnormalities. MR imaging of musculocutaneous cGVHD allows accurate evaluation including assessment of deep tissue infiltration and assists in the differential diagnosis. (orig.)

MR findings in patients with disabling musculocutaneous chronic graft-versus-host disease

International Nuclear Information System (INIS)

Horger, M.; Boss, A.; Claussen, C.D.; Bethge, W.; Faul, C.; Vogel, W.; Fierlbeck, G.; Bornemann, A.

2008-01-01

To describe musculocutaneous MR-findings responsible for disability in chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic cell transplantation (HCT). Between June 2005 and February 2008, we performed whole-body musculoskeletal magnetic resonance imaging (MRI; n = 12) or regional MRI (n = 4) in 16 consecutive patients presenting with disabling sclerodermatous cGVHD (e.g., skin edema, fixed deep dermal sclerosis, joint contractures, painful muscular contractures, or myalgia). In all patients, MRI showed musculocutaneous abnormalities reflecting different degrees of inflammation and collagen tissue involvement of the skin (n = 10), subcutaneous fat tissue (n 13), muscle fasciae (n = 16), subfascial muscular septae (n = 6), or findings compatible with myositis (n = 3). The most frequently involved muscle fasciae comprised those of the vastus lateralis muscle (n = 12), biceps femoris muscle (n = 11), gastrocnemius medialis muscle (n = 8), serratus anterior muscle, and latissimus dorsi muscle (each, n = 5). Increased signal of involved tissues on STIR-images and fat-saturated postgadolinium T1-weighted images represented the most frequent MR-signal abnormalities. MR imaging of musculocutaneous cGVHD allows accurate evaluation including assessment of deep tissue infiltration and assists in the differential diagnosis. (orig.)

Plant pathology: monitoring a pathogen-targeted host protein.

Science.gov (United States)

Ellis, Jeff; Dodds, Peter

2003-05-13

A plant protein RIN4 is targeted and modified by bacterial pathogens as part of the disease process. At least two host resistance proteins monitor this pathogen interference and trigger the plant's defence responses.

Mapping host-species abundance of three major exotic forest pests

Science.gov (United States)

Randall S. Morin; Andrew M. Liebhold; Eugene R. Luzader; Andrew J. Lister; Kurt W. Gottschalk; Daniel B. Twardus

2005-01-01

Periodically over the last century, forests of the Eastern United States devastated by invasive pests. We used existing data to predict the geographical extent of future damage from beech bark disease (BBD), hemlock woolly adelgid (HWA), and gypsy moth. The distributions of host species of these alien pests were mapped in 1-km2 cells by interpolating host basal area/ha...

Remote sensing for landscape epidemiology : spatial analysis of plague hosts in Kazakhstan

NARCIS (Netherlands)

Wilschut, L.I.

2015-01-01

The spatial distribution of hosts is a crucial aspect for the understanding of infectious disease dynamics. In Kazakhstan, the great gerbil (Rhombomys opimus) is the main host for plague (Yersinia pestis infection) and poses a public health threat, yet their spatial distribution is unknown. Great

Influence of the host contact sequence on the outcome of competition among aspergillus flavus isolates during host tissue invasion.

Science.gov (United States)

Mehl, H L; Cotty, P J

2011-03-01

Biological control of aflatoxin contamination by Aspergillus flavus is achieved through competitive exclusion of aflatoxin producers by atoxigenic strains. Factors dictating the extent to which competitive displacement occurs during host infection are unknown. The role of initial host contact in competition between pairs of A. flavus isolates coinfecting maize kernels was examined. Isolate success during tissue invasion and reproduction was assessed by quantification of isolate-specific single nucleotide polymorphisms using pyrosequencing. Isolates were inoculated either simultaneously or 1 h apart. Increased success during competition was conferred to the first isolate to contact the host independent of that isolate's innate competitive ability. The first-isolate advantage decreased with the conidial concentration, suggesting capture of limited resources on kernel surfaces contributes to competitive exclusion. Attempts to modify access to putative attachment sites by either coating kernels with dead conidia or washing kernels with solvents did not influence the success of the first isolate, suggesting competition for limited attachment sites on kernel surfaces does not mediate first-isolate advantage. The current study is the first to demonstrate an immediate competitive advantage conferred to A. flavus isolates upon host contact and prior to either germ tube emergence or host colonization. This suggests the timing of host contact is as important to competition during disease cycles as innate competitive ability. Early dispersal to susceptible crop components may allow maintenance within A. flavus populations of genetic types with low competitive ability during host tissue invasion.

Host-to-host variation of ecological interactions in polymicrobial infections

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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.

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.

Host adaptation of bovine Staphylococcus aureus seems associated with bacteriological cure after lactational antimicrobial treatment

NARCIS (Netherlands)

Borne, van den B.H.P.; Nielen, M.; Schaik, van G.; Melchior, M.B.; Lam, T.J.G.M.; Zadoks, R.N.

2010-01-01

Staphylococcus aureus causes a wide range of diseases in multiple species. Some sequence types (ST) are observed in a variety of hosts, whereas other strains are mainly associated with bovine mastitis, suggesting host adaptation. We propose that host adaptation of Staph. aureus may influence

Do parasitic trematode cercariae demonstrate a preference for susceptible host species?

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Brittany F Sears

Full Text Available Many parasites are motile and exhibit behavioural preferences for certain host species. Because hosts can vary in their susceptibility to infections, parasites might benefit from preferentially detecting and infecting the most susceptible host, but this mechanistic hypothesis for host-choice has rarely been tested. We evaluated whether cercariae (larval trematode parasites prefer the most susceptible host species by simultaneously presenting cercariae with four species of tadpole hosts. Cercariae consistently preferred hosts in the following order: Anaxyrus ( = Bufo terrestris (southern toad, Hyla squirella (squirrel tree frog, Lithobates ( = Rana sphenocephala (southern leopard frog, and Osteopilus septentrionalis (Cuban tree frog. These host species varied in susceptibility to cercariae in an order similar to their attractiveness with a correlation that approached significance. Host attractiveness to parasites also varied consistently and significantly among individuals within a host species. If heritable, this individual-level host variation would represent the raw material upon which selection could act, which could promote a Red Queen "arms race" between host cues and parasite detection of those cues. If, in general, motile parasites prefer to infect the most susceptible host species, this phenomenon could explain aggregated distributions of parasites among hosts and contribute to parasite transmission rates and the evolution of virulence. Parasite preferences for hosts belie the common assumption of disease models that parasites seek and infect hosts at random.

The phloem-sap feeding mealybug (Ferrisia virgata carries 'Candidatus Liberibacter asiaticus' populations that do not cause disease in host plants.

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Marco Pitino

Full Text Available 'Candidatus Liberibacter asiaticus' (Las is the primary causal agent of huanglongbing (HLB, the most devastating disease of citrus worldwide. There are three known insect vectors of the HLB-associated bacteria, and all are members of the Hemiptera: Diaphorina citri (Psyllidae, Trioza erytreae (Triozidae, and Cacopsylla (Psylla citrisuga (Psyllidae. In this study, we found that another hemipteran, the striped mealybug Ferrisia virgata (Cockerell (Hemiptera: Pseudococcidae, was able to acquire and retain Las bacteria. The bacterial titers were positively correlated with the feeding acquisition time on Las-infected leaf discs, with a two-weeks feeding period resulting in Ct values ranging from 23.1 to 36.1 (8.24 × 10(7 to 1.07 × 10(4 Las cells per mealybug. We further discovered that the prophage/phage populations of Las in the mealybugs were different from those of Las in psyllids based on Las prophage-specific molecular markers: infected psyllids harbored the Las populations with prophage/phage FP1 and FP2, while infected mealybugs carried the Las populations with the iFP3 being the dominant prophage/phage. As in the psyllids, Las bacteria were shown to move through the insect gut wall to the salivary glands after being ingested by the mealybug based on a time-course quantitative polymerase chain reaction (qPCR assay of the dissected digestive systems. However, Las populations transmitted by the mealybugs did not cause disease in host plants. This is the first evidence of genetic difference among Las populations harbored by different insect vectors and difference among Las populations with respect to whether or not they cause disease in host plants.

Granzyme A Is Required for Regulatory T-Cell Mediated Prevention of Gastrointestinal Graft-versus-Host Disease.

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Sarvari Velaga

Full Text Available In our previous work we could identify defects in human regulatory T cells (Tregs likely favoring the development of graft-versus-host disease (GvHD following allogeneic stem cell transplantation (SCT. Treg transcriptome analyses comparing GvHD and immune tolerant patients uncovered regulated gene transcripts highly relevant for Treg cell function. Moreover, granzyme A (GZMA also showed a significant lower expression at the protein level in Tregs of GvHD patients. GZMA induces cytolysis in a perforin-dependent, FAS-FASL independent manner and represents a cell-contact dependent mechanism for Tregs to control immune responses. We therefore analyzed the functional role of GZMA in a murine standard model for GvHD. For this purpose, adoptively transferred CD4+CD25+ Tregs from gzmA-/- mice were analyzed in comparison to their wild type counterparts for their capability to prevent murine GvHD. GzmA-/- Tregs home efficiently to secondary lymphoid organs and do not show phenotypic alterations with respect to activation and migration properties to inflammatory sites. Whereas gzmA-/- Tregs are highly suppressive in vitro, Tregs require GZMA to rescue hosts from murine GvHD, especially regarding gastrointestinal target organ damage. We herewith identify GZMA as critical effector molecule of human Treg function for gastrointestinal immune response in an experimental GvHD model.

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

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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...

Commensal Homeostasis of Gut Microbiota-Host for the Impact of Obesity

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Pengyi Zhang

2018-01-01

Full Text Available Gut microbiota and their metabolites have been linked to a series of chronic diseases such as obesity and other metabolic dysfunctions. Obesity is an increasingly serious international health issue that may lead to a risk of insulin resistance and other metabolic diseases. The relationship between gut microbiota and the host is both interdependent and relatively independent. In this review, the causality of gut microbiota and its role in the pathogenesis and intervention of obesity is comprehensively presented to include human genotype, enterotypes, interactions of gut microbiota with the host, microbial metabolites, and energy homeostasis all of which may be influenced by dietary nutrition. Diet can enhance, inhibit, or even change the composition and functions of the gut microbiota. The metabolites they produce depend upon the dietary substrates provided, some of which have indispensable functions for the host. Therefore, diet is a key factor that maintains or not a healthy commensal relationship. In addition, the specific genotype of the host may impact the phylogenetic compositions of gut microbiota through the production of host metabolites. The commensal homeostasis of gut microbiota is favored by a balance of microbial composition, metabolites, and energy. Ultimately the desired commensal relationship is one of mutual support. This article analyzes the clues that result in patterns of commensal homeostasis. A deeper understanding of these interactions is beneficial for developing effective prevention, diagnosis, and personalized therapeutic strategies to combat obesity and other metabolic diseases. The idea we discuss is meant to improve human health by shaping or modulating the beneficial gut microbiota.

Lawrence Livermore National Laboratory Workshop Characterization of Pathogenicity, Virulence and Host-Pathogen Interactions

Energy Technology Data Exchange (ETDEWEB)

Krishnan, A

2006-08-30

The threats of bio-terrorism and newly emerging infectious diseases pose serious challenges to the national security infrastructure. Rapid detection and diagnosis of infectious disease in human populations, as well as characterizing pathogen biology, are critical for reducing the morbidity and mortality associated with such threats. One of the key challenges in managing an infectious disease outbreak, whether through natural causes or acts of overt terrorism, is detection early enough to initiate effective countermeasures. Much recent attention has been directed towards the utility of biomarkers or molecular signatures that result from the interaction of the pathogen with the host for improving our ability to diagnose and mitigate the impact of a developing infection during the time window when effective countermeasures can be instituted. Host responses may provide early signals in blood even from localized infections. Multiple innate and adaptive immune molecules, in combination with other biochemical markers, may provide disease-specific information and new targets for countermeasures. The presence of pathogen specific markers and an understanding of the molecular capabilities and adaptations of the pathogen when it interacts with its host may likewise assist in early detection and provide opportunities for targeting countermeasures. An important question that needs to be addressed is whether these molecular-based approaches will prove useful for early diagnosis, complement current methods of direct agent detection, and aid development and use of countermeasures. Lawrence Livermore National Laboratory (LLNL) will host a workshop to explore the utility of host- and pathogen-based molecular diagnostics, prioritize key research issues, and determine the critical steps needed to transition host-pathogen research to tools that can be applied towards a more effective national bio-defense strategy. The workshop will bring together leading researchers/scientists in the

Lethal graft-versus-host disease: modification with allogeneic cultured donor cells

International Nuclear Information System (INIS)

Mauch, P.; Lipton, J.M.; Hamilton, B.; Obbagy, J.; Kudisch, M.; Nathan, D.; Hellman, S.

1984-01-01

The use of the bone marrow culture technique was studied as a means to prepare donor marrow for bone marrow transplantation to avoid lethal graft-versus-host disease (GVHD). Preliminary experiments demonstrated the rapid loss of theta-positive cells in such cultures, so that theta-positive cells were not detected after 6 days. Initial experiments in C3H/HeJ (H-2k, Hbbd) recipients prepared with 900 rad demonstrated improved survival when 3-day cultured C57BL/6 (H-2b, Hbbs) donor cells were used in place of hind limb marrow for transplantation. However, hemoglobin typing of recipient animals revealed only short-term donor engraftment, with competitive repopulation of recipient marrow occurring. Subsequent experiments were done in 1,200-rad prepared recipients, with long-term donor engraftment demonstrated. The majority of 1,200-rad prepared animals receiving cultured allogeneic cells died of GVHD, but animals receiving 28-day cultured cells had an improved 90-day survival and a delay in GVHD development over animals receiving hind limb marrow or marrow from shorter times in culture. In addition, animals receiving anti-theta-treated, 3-day nonadherent cells had an improved survival (44%) over animals receiving anti-theta-treated hind limb marrow (20%). These experiments demonstrate modest benefit for the use of cultured cells in bone marrow transplantation across major H-2 histocompatibility complex differences

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)

Usefulness of blood irradiation before transfusion to avoid transfusion associated graft versus host disease (TA-GVHD)

International Nuclear Information System (INIS)

Takahashi, Koki

1997-01-01

We summarize the pathology of the transfusion associated graft versus host disease (TA-GVHD) and examine the usefulness of the blood irradiation before transfusion as more widely used prophylaxis. The symptom of TA-GVHD was as follows: after (asymptomatic phase) for 1 to 2 weeks after blood transfusion, pyrexia and erythema appeared. Furthermore, hepatic disorder, diarrhea and bloody stool occurred. In no longer time, pancytopenia by aplastic crisis of the bone marrow appeard, and severe granulocytopenia occurred. Finally, by the complication with severe infectious disease such as septicemia, almost all the patients died with in 3 to 4 weeks after blood transfusion. TA-GVHD was found in some patients without immune deficiency syndrome. The cause of the frequent occurrence of the disease in Japan was shown by the probability of the one-way matching analysis. As the countermeasure of TA-GVHD, we examined the effectiveness of the blood irradiation before transfusion under the consideration of the safety and the emergency. After the responder cells were beforehand irradiated with various doses of radiation (X-ray or g-ray), the proliferative response was investigated through the uptake of 3 H-thymidine, and we obtained 15-50 Gy as the optimum dose of the radiation. We discuss the establishment of the countermeasure for the TA-GVHD and the formation of the nationwide support system for TV-GVHD (K.H.). 33 refs

Gut Microbiota Co-microevolution with Selection for Host Humoral Immunity

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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.

[Extracorporeal photopheresis as an alternative therapy for drug-resistant graft versus host disease: three cases].

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D'incan, M; Kanold, J; Halle, P; De Lumley, L; Souteyrand, P; Deméocq, F

2000-02-01

Graft versus host reaction is a life-threatening complication of allogenic bone marrow transplantation. Extracorporeal photopheresis has been used for some years in the treatment of graft versus host reaction. We report on three children treated with extracorporeal photopheresis for a graft versus host reaction resistant to immunosuppresive drugs. Three children with a graft versus host reaction were submitted to 18, 30 and 46 extracorporeal photopheresis courses respectively. In the same time, the other immunosuppressive treatments were tapered or definitively stopped (ciclosporin). A dramatic improvement of cutaneous status and biological data was observed after the first courses. However, the extracorporeal photopheresis treatment did not improve the mucous lesions. No serious adverse effect was encountered. As published elsewhere, extracorporeal photopheresis was effective on the graft versus host reaction lichenoid cutaneous lesions and in case of visceral involvement. In all of our cases, the immunosuppressive drug could have been tapered. No adverse event was observed. Thus, extracorporeal photopheresis should be indicated in case of resistance to immunosuppressive drugs.

Genetic structure and natural variation associated with host of origin in Penicillium expansum strains causing blue mould.

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Sanzani, S M; Montemurro, C; Di Rienzo, V; Solfrizzo, M; Ippolito, A

2013-07-15

Blue mould, caused by Penicillium expansum, is one of the most economically damaging postharvest diseases of pome fruits, although it may affect a wider host range, including sweet cherries and table grapes. Several reports on the role of mycotoxins in plant pathogenesis have been published, but few focussed on the influence of mycotoxins on the variation in host preference amongst producing fungi. In the present study the influence of the host on P. expansum pathogenicity/virulence was investigated, focussing mainly on the relationship with patulin production. Three P. expansum strain groups, originating from apples, sweet cherries, and table grapes (7 strains per host) were grown on their hosts of isolation and on artificial media derived from them. Strains within each P. expansum group proved to be more aggressive and produced more patulin than the other two groups under evaluation when grown on the host from which they originated. Table grape strains were the most aggressive (81% disease incidence) and strongest patulin producers (up to 554μg/g). The difference in aggressiveness amongst strains was appreciable only in the presence of a living host, suggesting that the complex pathogen-host interaction significantly influenced the ability of P. expansum to cause the disease. Incidence/severity of the disease and patulin production proved to be positively correlated, supporting the role of patulin as virulence/pathogenicity factor. The existence of genetic variation amongst isolates was confirmed by the High Resolution Melting method that was set up herein, which permitted discrimination of P. expansum from other species (P. chrysogenum and P. crustosum) and, within the same species, amongst the host of origin. Host effect on toxin production appeared to be exerted at a transcriptional level. Copyright © 2013 Elsevier B.V. All rights reserved.

Ceacam1 separates graft-versus-host-disease from graft-versus-tumor activity after experimental allogeneic bone marrow transplantation.

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Sydney X Lu

Full Text Available Allogeneic bone marrow transplantation (allo-BMT is a potentially curative therapy for a variety of hematologic diseases, but benefits, including graft-versus-tumor (GVT activity are limited by graft-versus-host-disease (GVHD. Carcinoembryonic antigen related cell adhesion molecule 1 (Ceacam1 is a transmembrane glycoprotein found on epithelium, T cells, and many tumors. It regulates a variety of physiologic and pathological processes such as tumor biology, leukocyte activation, and energy homeostasis. Previous studies suggest that Ceacam1 negatively regulates inflammation in inflammatory bowel disease models.We studied Ceacam1 as a regulator of GVHD and GVT after allogeneic bone marrow transplantation (allo-BMT in mouse models. In vivo, Ceacam1(-/- T cells caused increased GVHD mortality and GVHD of the colon, and greater numbers of donor T cells were positive for activation markers (CD25(hi, CD62L(lo. Additionally, Ceacam1(-/- CD8 T cells had greater expression of the gut-trafficking integrin α(4β(7, though both CD4 and CD8 T cells were found increased numbers in the gut post-transplant. Ceacam1(-/- recipients also experienced increased GVHD mortality and GVHD of the colon, and alloreactive T cells displayed increased activation. Additionally, Ceacam1(-/- mice had increased mortality and decreased numbers of regenerating small intestinal crypts upon radiation exposure. Conversely, Ceacam1-overexpressing T cells caused attenuated target-organ and systemic GVHD, which correlated with decreased donor T cell numbers in target tissues, and mortality. Finally, graft-versus-tumor survival in a Ceacam1(+ lymphoma model was improved in animals receiving Ceacam1(-/- vs. control T cells.We conclude that Ceacam1 regulates T cell activation, GVHD target organ damage, and numbers of donor T cells in lymphoid organs and GVHD target tissues. In recipients of allo-BMT, Ceacam1 may also regulate tissue radiosensitivity. Because of its expression on both the

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

Host-microbiota interplay in mediating immune disorders.

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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.

COMPARISON OF IN VITRO-CULTURED AND WILD-TYPE PERKINSUS MARINUS. II: DOSING METHODS AND HOST RESPONSE

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Endoparasites must breach host barriers to establish infection and then must survive host internal defenses to cause disease. Such barriers may frustrate attempts to experimentally transmit parasites by ?natural' methods. In addition, the host's condition may affect a study's out...

Host response to Brucella infection: review and future perspective.

Science.gov (United States)

Elfaki, Mohamed G; Alaidan, Alwaleed Abdullah; Al-Hokail, Abdullah Abdulrahman

2015-07-30

Brucellosis is a zoonotic and contagious infectious disease caused by infection with Brucella species. The infecting brucellae are capable of causing a devastating multi-organ disease in humans with serious health complications. The pathogenesis of Brucella infection is influenced largely by host factors, Brucella species/strain, and the ability of invading brucellae to survive and replicate within mononuclear phagocytic cells, preferentially macrophages (Mf). Consequently, the course of human infection may appear as an acute fatal or progress into chronic debilitating infection with periodical episodes that leads to bacteremia and death. The existence of brucellae inside Mf represents one of the strategies used by Brucella to evade the host immune response and is responsible for treatment failure in certain human populations treated with anti-Brucella drugs. Moreover, the persistence of brucellae inside Mf complicates the diagnosis and may affect the host cell signaling pathways with consequent alterations in both innate and adaptive immune responses. Therefore, there is an urgent need to pursue the development of novel drugs and/or vaccine targets against human brucellosis using high throughput technologies in genomics, proteomics, and immunology.

Prevalence, Genetic Characterization, and 18S Small Subunit Ribosomal RNA Diversity of Trypanosoma rangeli in Triatomine and Mammal Hosts in Endemic Areas for Chagas Disease in Ecuador.

Science.gov (United States)

Ocaña-Mayorga, Sofia; Aguirre-Villacis, Fernanda; Pinto, C Miguel; Vallejo, Gustavo A; Grijalva, Mario J

2015-12-01

Trypanosoma rangeli is a nonpathogenic parasite for humans; however, its medical importance relies in its similarity and overlapping distribution with Trypanosoma cruzi, causal agent of Chagas disease in the Americas. The genetic diversity of T. rangeli and its association with host species (triatomines and mammals) has been identified along Central and the South America; however, it has not included data of isolates from Ecuador. This study reports infection with T. rangeli in 18 genera of mammal hosts and five species of triatomines in three environments (domestic, peridomestic, and sylvatic). Higher infection rates were found in the sylvatic environment, in close association with Rhodnius ecuadoriensis. The results of this study extend the range of hosts infected with this parasite and the geographic range of the T. rangeli genotype KP1(-)/lineage C in South America. It was not possible to detect variation on T. rangeli from the central coastal region and southern Ecuador with the analysis of the small subunit ribosomal RNA (SSU-rRNA) gene, even though these areas are ecologically different and a phenotypic subdivision of R. ecuadoriensis has been found. R. ecuadoriensis is considered one of the most important vectors for Chagas disease transmission in Ecuador due to its wide distribution and adaptability to diverse environments. An extensive knowledge of the trypanosomes circulating in this species of triatomine, and associated mammal hosts, is important for delineating transmission dynamics and preventive measures in the endemic areas of Ecuador and Northern Peru.

Prevalence, Genetic Characterization, and 18S Small Subunit Ribosomal RNA Diversity of Trypanosoma rangeli in Triatomine and Mammal Hosts in Endemic Areas for Chagas Disease in Ecuador

Science.gov (United States)

Ocaña-Mayorga, Sofia; Aguirre-Villacis, Fernanda; Pinto, C. Miguel; Vallejo, Gustavo A.

2015-01-01

Abstract Trypanosoma rangeli is a nonpathogenic parasite for humans; however, its medical importance relies in its similarity and overlapping distribution with Trypanosoma cruzi, causal agent of Chagas disease in the Americas. The genetic diversity of T. rangeli and its association with host species (triatomines and mammals) has been identified along Central and the South America; however, it has not included data of isolates from Ecuador. This study reports infection with T. rangeli in 18 genera of mammal hosts and five species of triatomines in three environments (domestic, peridomestic, and sylvatic). Higher infection rates were found in the sylvatic environment, in close association with Rhodnius ecuadoriensis. The results of this study extend the range of hosts infected with this parasite and the geographic range of the T. rangeli genotype KP1(−)/lineage C in South America. It was not possible to detect variation on T. rangeli from the central coastal region and southern Ecuador with the analysis of the small subunit ribosomal RNA (SSU-rRNA) gene, even though these areas are ecologically different and a phenotypic subdivision of R. ecuadoriensis has been found. R. ecuadoriensis is considered one of the most important vectors for Chagas disease transmission in Ecuador due to its wide distribution and adaptability to diverse environments. An extensive knowledge of the trypanosomes circulating in this species of triatomine, and associated mammal hosts, is important for delineating transmission dynamics and preventive measures in the endemic areas of Ecuador and Northern Peru. PMID:26645579

Patterns of coral disease across the Hawaiian archipelago: relating disease to environment.

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Greta S Aeby

Full Text Available In Hawaii, coral reefs occur across a gradient of biological (host abundance, climatic (sea surface temperature anomalies and anthropogenic conditions from the human-impacted reefs of the main Hawaiian Islands (MHI to the pristine reefs of the northwestern Hawaiian Islands (NWHI. Coral disease surveys were conducted at 142 sites from across the Archipelago and disease patterns examined. Twelve diseases were recorded from three coral genera (Porites, Montipora, Acropora with Porites having the highest prevalence. Porites growth anomalies (PorGAs were significantly more prevalent within and indicative of reefs in the MHI and Porites trematodiasis (PorTrm was significantly more prevalent within and indicative of reefs in the NWHI. Porites tissue loss syndrome (PorTLS was also important in driving regional differences but that relationship was less clear. These results highlight the importance of understanding disease ecology when interpreting patterns of disease occurrence. PorTrm is caused by a parasitic flatworm that utilizes multiple hosts during its life cycle (fish, mollusk and coral. All three hosts must be present for the disease to occur and higher host abundance leads to higher disease prevalence. Thus, a high prevalence of PorTrm on Hawaiian reefs would be an indicator of a healthy coral reef ecosystem. In contrast, the high occurrence of PorGAs within the MHI suggests that PorGAs are related, directly or indirectly, to some environmental co-factor associated with increased human population sizes. Focusing on the three indicator diseases (PorGAs, PorTrm, PorTLS we used statistical modeling to examine the underlying associations between disease prevalence and 14 different predictor variables (biotic and abiotic. All three diseases showed positive associations with host abundance and negative associations with thermal stress. The association with human population density differed among disease states with PorGAs showing a positive and Por

Patterns of coral disease across the Hawaiian Archipelago: Relating disease to environment

Science.gov (United States)

Aeby, G.S.; Williams, G.J.; Franklin, E.C.; Kenyon, J.; Cox, E.F.; Coles, S.; Work, Thierry M.

2011-01-01

In Hawaii, coral reefs occur across a gradient of biological (host abundance), climatic (sea surface temperature anomalies) and anthropogenic conditions from the human-impacted reefs of the main Hawaiian Islands (MHI) to the pristine reefs of the northwestern Hawaiian Islands (NWHI). Coral disease surveys were conducted at 142 sites from across the Archipelago and disease patterns examined. Twelve diseases were recorded from three coral genera (Porites, Montipora, Acropora) with Porites having the highest prevalence. Porites growth anomalies (PorGAs) were significantly more prevalent within and indicative of reefs in the MHI and Porites trematodiasis (PorTrm) was significantly more prevalent within and indicative of reefs in the NWHI. Porites tissue loss syndrome (PorTLS) was also important in driving regional differences but that relationship was less clear. These results highlight the importance of understanding disease ecology when interpreting patterns of disease occurrence. PorTrm is caused by a parasitic flatworm that utilizes multiple hosts during its life cycle (fish, mollusk and coral). All three hosts must be present for the disease to occur and higher host abundance leads to higher disease prevalence. Thus, a high prevalence of PorTrm on Hawaiian reefs would be an indicator of a healthy coral reef ecosystem. In contrast, the high occurrence of PorGAs within the MHI suggests that PorGAs are related, directly or indirectly, to some environmental co-factor associated with increased human population sizes. Focusing on the three indicator diseases (PorGAs, PorTrm, PorTLS) we used statistical modeling to examine the underlying associations between disease prevalence and 14 different predictor variables (biotic and abiotic). All three diseases showed positive associations with host abundance and negative associations with thermal stress. The association with human population density differed among disease states with PorGAs showing a positive and PorTrm showing

Salmonella Intracellular Lifestyles and Their Impact on Host-to-Host Transmission.

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Pucciarelli, M Graciela; García-Del Portillo, Francisco

2017-07-01

More than a century ago, infections by Salmonella were already associated with foodborne enteric diseases with high morbidity in humans and cattle. Intestinal inflammation and diarrhea are hallmarks of infections caused by nontyphoidal Salmonella serovars, and these pathologies facilitate pathogen transmission to the environment. In those early times, physicians and microbiologists also realized that typhoid and paratyphoid fever caused by some Salmonella serovars could be transmitted by "carriers," individuals outwardly healthy or at most suffering from some minor chronic complaint. In his pioneering study of the nontyphoidal serovar Typhimurium in 1967, Takeuchi published the first images of intracellular bacteria enclosed by membrane-bound vacuoles in the initial stages of the intestinal epithelium penetration. These compartments, called Salmonella -containing vacuoles, are highly dynamic phagosomes with differing biogenesis depending on the host cell type. Single-cell studies involving real-time imaging and gene expression profiling, together with new approaches based on genetic reporters sensitive to growth rate, have uncovered unprecedented heterogeneous responses in intracellular bacteria. Subpopulations of intracellular bacteria displaying fast, reduced, or no growth, as well as cytosolic and intravacuolar bacteria, have been reported in both in vitro and in vivo infection models. Recent investigations, most of them focused on the serovar Typhimurium, point to the selection of persisting bacteria inside macrophages or following an autophagy attack in fibroblasts. Here, we discuss these heterogeneous intracellular lifestyles and speculate on how these disparate behaviors may impact host-to-host transmissibility of Salmonella serovars.

Lipid exchange between Borrelia burgdorferi and host cells.

Directory of Open Access Journals (Sweden)

Jameson T Crowley

2013-01-01

Full Text Available Borrelia burgdorferi, the agent of Lyme disease, has cholesterol and cholesterol-glycolipids that are essential for bacterial fitness, are antigenic, and could be important in mediating interactions with cells of the eukaryotic host. We show that the spirochetes can acquire cholesterol from plasma membranes of epithelial cells. In addition, through fluorescent and confocal microscopy combined with biochemical approaches, we demonstrated that B. burgdorferi labeled with the fluorescent cholesterol analog BODIPY-cholesterol or (3H-labeled cholesterol transfer both cholesterol and cholesterol-glycolipids to HeLa cells. The transfer occurs through two different mechanisms, by direct contact between the bacteria and eukaryotic cell and/or through release of outer membrane vesicles. Thus, two-way lipid exchange between spirochetes and host cells can occur. This lipid exchange could be an important process that contributes to the pathogenesis of Lyme disease.

The Ecology of Parasite-Host Interactions at Montezuma Well National Monument, Arizona - Appreciating the Importance of Parasites

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O'Brien, Chris; van Riper, Charles

2009-01-01

Although parasites play important ecological roles through the direct interactions they have with their hosts, historically that fact has been underappreciated. Today, scientists have a growing appreciation of the scope of such impacts. Parasites have been reported to dominate food webs, alter predator-prey relationships, act as ecosystem engineers, and alter community structure. In spite of this growing awareness in the scientific community, parasites are still often neglected in the consideration of the management and conservation of resources and ecosystems. Given that at least half of the organisms on earth are probably parasitic, it should be evident that the ecological functions of parasites warrant greater attention. In this report, we explore different aspects of parasite-host relationships found at a desert spring pond within Montezuma Well National Monument, Arizona. In three separate but related chapters, we explore interactions between a novel amphipod host and two parasites. First, we identify how host behavior responds to this association and how this association affects interactions with both invertebrate non-host predators and a vertebrate host predator. Second, we look at the human dimension, investigating how human recreation can indirectly affect patterns of disease by altering patterns of vertebrate host space use. Finally - because parasites and diseases are of increasing importance in the management of wildlife species, especially those that are imperiled or of management concern - the third chapter argues that research would benefit from increased attention to the statistical analysis of wildlife disease studies. This report also explores issues of statistical parasitology, providing information that may better inform those designing research projects and analyzing data from studies of wildlife disease. In investigating the nature of parasite-host interactions, the role that relationships play in ecological communities, and how human

Host-Directed Therapeutics as a Novel Approach for Tuberculosis Treatment.

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Kim, Ye-Ram; Yang, Chul-Su

2017-09-28

Despite significant efforts to improve the treatment of tuberculosis (TB), it remains a prevalent infectious disease worldwide owing to the limitations of current TB therapeutic regimens. Recent work on novel TB treatment strategies has suggested that directly targeting host factors may be beneficial for TB treatment. Such strategies, termed host-directed therapeutics (HDTs), focus on host-pathogen interactions. HDTs may be more effective than the currently approved TB drugs, which are limited by the long durations of treatment needed and the emergence of drug-resistant strains. Targets of HDTs include host factors such as cytokines, immune checkpoints, immune cell functions, and essential enzyme activities. This review article discusses examples of potentially promising HDTs and introduces novel approaches for their development.

Diversity and environmental relations of cryptic, systemic Botrytis infections in symptomless hosts.

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Michael W. Shaw

2016-05-01

Full Text Available Botrytis species are generally considered to be aggressive, necrotrophic plant pathogens. By contrast to this general perception, however, Botrytis species could frequently be isolated from the interior of multiple tissues in apparently healthy hosts of many species. Infection frequencies reached 50% of samples or more, but were commonly less, and cryptic infections were rare or absent in some plant species. Prevalence varied substantially from year to year and from tissue to tissue, but some host species routinely had high prevalence. The same genotype was found to occur throughout a host, representing mycelial spread. B. cinerea and B. pseudocinerea are the species that most commonly occur as cryptic infections, but phylogenetically distant isolates of Botrytis were also detected, one of which does not correspond to previously described species. Sporulation and visible damage occurred only when infected tissues were stressed, or became mature or senescent. There was no evidence of cryptic infection having a deleterious effect on growth of the host, and prevalence was probably greater in plants grown in high light conditions. Isolates from cryptic infections were often capable of causing disease (to varying extents when spore suspensions were inoculated onto their own host as well as on distinct host species, arguing against co-adaptation between cryptic isolates and their hosts. These data collectively suggest that several Botrytis species, including the most notorious pathogenic species, exist frequently in cryptic form to an extent that has thus far largely been neglected, and do not need to cause disease on healthy hosts in order to complete their life-cycles.

Parasite transmission in social interacting hosts: Monogenean epidemics in guppies

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Johnson, Mirelle B.; Lafferty, Kevin D.; van Oosterhout, Cock; Cable, Joanne

2011-01-01

Background Infection incidence increases with the average number of contacts between susceptible and infected individuals. Contact rates are normally assumed to increase linearly with host density. However, social species seek out each other at low density and saturate their contact rates at high densities. Although predicting epidemic behaviour requires knowing how contact rates scale with host density, few empirical studies have investigated the effect of host density. Also, most theory assumes each host has an equal probability of transmitting parasites, even though individual parasite load and infection duration can vary. To our knowledge, the relative importance of characteristics of the primary infected host vs. the susceptible population has never been tested experimentally. Methodology/Principal Findings Here, we examine epidemics using a common ectoparasite, Gyrodactylus turnbulli infecting its guppy host (Poecilia reticulata). Hosts were maintained at different densities (3, 6, 12 and 24 fish in 40 L aquaria), and we monitored gyrodactylids both at a population and individual host level. Although parasite population size increased with host density, the probability of an epidemic did not. Epidemics were more likely when the primary infected fish had a high mean intensity and duration of infection. Epidemics only occurred if the primary infected host experienced more than 23 worm days. Female guppies contracted infections sooner than males, probably because females have a higher propensity for shoaling. Conclusions/Significance These findings suggest that in social hosts like guppies, the frequency of social contact largely governs disease epidemics independent of host density.

Temporal, geographic, and host distribution of avian paramyxovirus 1 (Newcastle disease virus)

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Dimitrov, Kiril M.; Ramey, Andy M.; Qiu, Xueting; Bahl, Justin; Afonso, Claudio L.

2016-01-01

Newcastle disease is caused by virulent forms of avian paramyxovirus of serotype 1 (APMV-1) and has global economic importance. The disease reached panzootic proportions within two decades after first being identified in 1926 in the United Kingdom and Indonesia and still remains endemic in many countries across the world. Here we review information on the host, temporal, and geographic distribution of APMV-1 genetic diversity based on the evolutionary systematics of the complete coding region of the fusion gene. Strains of APMV-1 are phylogenetically separated into two classes (class I and class II) and further classified into genotypes based on genetic differences. Class I viruses are genetically less diverse, generally present in wild waterfowl, and are of low virulence. Class II viruses are genetically and phenotypically more diverse, frequently isolated from poultry with occasional spillovers into wild birds, and exhibit a wider range of virulence. Waterfowl, cormorants, and pigeons are natural reservoirs of all APMV-1 pathotypes, except viscerotropic velogenic viruses for which natural reservoirs have not been identified. Genotypes I and II within class II include isolates of high and low virulence, the latter often being used as vaccines. Viruses of genotypes III and IX that emerged decades ago are now isolated rarely, but may be found in domestic and wild birds in China. Containing only virulent viruses and responsible for the majority of recent outbreaks in poultry and wild birds, viruses from genotypes V, VI, and VII, are highly mobile and have been isolated on different continents. Conversely, virulent viruses of genotypes XI (Madagascar), XIII (mainly Southwest Asia), XVI (North America) and XIV, XVII and XVIII (Africa) appear to have a more limited geographic distribution and have been isolated predominantly from poultry.

Probing Pseudomonas syringae host interactions using metatranscriptomics

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Transcriptome analyses during the interaction of plants and pathogens can be used to provide insights into molecular mechanisms of plant resistance as well as the mechanisms used by bacteria to adapt to hosts and cause disease. We performed a dual in planta RNA-Seq experiment to profile RNA expressi...

Salmonella Typhimurium metabolism affects virulence in the host – A mini-review

DEFF Research Database (Denmark)

Herrero-fresno, Ana; Olsen, John Elmerdhahl

2018-01-01

Salmonella enterica remains an important food borne pathogen in all regions of the world with S. Typhimurium as one of the most frequent serovars causing food borne disease. Since the majority of human cases are caused by food of animal origin, there has been a high interest in understanding how S....... Typhimurium interacts with the animal host, mostly focusing on factors that allow it to breach host barriers and to manipulate host cells to the benefit of itself. Up to recently, such studies have ignored the metabolic factors that allow the bacteria to multiply in the host, but this is changing rapidly...

OSI-027 modulates acute graft-versus-host disease after liver transplantation in a rat model.

Science.gov (United States)

Zhi, Xiao; Xue, Fei; Chen, Wei; Liang, Chao; Liu, Hao; Ma, Tao; Xia, Xuefeng; Hu, Liqiang; Bai, Xueli; Liang, Tingbo

2017-09-01

Despite its rarity (1%-2%), acute graft-versus-host disease after liver transplantation (LT-aGVHD) has a high mortality rate (85%). A gradual decrease in regulatory T cells (Tregs) correlates with disease progression in a rat LT-GVHD model, and treatments which increase Tregs exert therapeutic effects on LT-aGVHD. In this study, LT-aGVHD model rats were treated with rapamycin (RAPA), OSI-027, or an equal quantity of vehicle. Rats treated with OSI-027 survived longer (>100 days) than those in the RAPA (70 ± 8 days) or control (24 ± 3 days) groups. Flow cytometric analysis showed that the Treg ratios in peripheral blood mononuclear cells in the OSI-027 group were higher than those in the RAPA or control groups. The proportions of donor-derived lymphocytes in the OSI-027 group were lower than those in the RAPA or control groups. Hematoxylin-eosin staining of skin tissue demonstrated less severe lymphocyte infiltration in the OSI-027 group than that in the RAPA or control groups. In vitro, OSI-027 induced differentiation of CD4 + CD25 - T cells into CD4 + CD25 + forkhead box P3 + Tregs. Furthermore, injection of OSI-027-induced donor-derived CD4 + CD25 + T cells into the peripheral blood of LT-aGVHD model rats prevented LT-aGVHD. Thus, OSI-027 is implicated as a novel method for the treatment of LT-aGVHD. Liver Transplantation 23 1186-1198 2017 AASLD. © 2017 by the American Association for the Study of Liver Diseases.

Reciprocal Hosts' Responses to Powdery Mildew Isolates Originating from Domesticated Wheats and Their Wild Progenitor.

Science.gov (United States)

Ben-David, Roi; Dinoor, Amos; Peleg, Zvi; Fahima, Tzion

2018-01-01

The biotroph wheat powdery mildew, Blumeria graminis (DC.) E.O. Speer, f. sp. tritici Em. Marchal ( Bgt ), has undergone long and dynamic co-evolution with its hosts. In the last 10,000 years, processes involved in plant evolution under domestication, altered host-population structure. Recently both virulence and genomic profiling separated Bgt into two groups based on their origin from domestic host and from wild emmer wheat. While most studies focused on the Bgt pathogen, there is significant knowledge gaps in the role of wheat host diversity in this specification. This study aimed to fill this gap by exploring qualitatively and also quantitatively the disease response of diverse host panel to powdery mildew [105 domesticated wheat genotypes ( Triticum turgidum ssp. dicoccum, T. turgidum ssp. durum , and T. aestivum ) and 241 accessions of its direct progenitor, wild emmer wheat ( T. turgidum ssp. dicoccoides )]. A set of eight Bgt isolates, originally collected from domesticated and wild wheat was used for screening this wheat collection. The isolates from domesticated wheat elicited susceptible to moderate plant responses on domesticated wheat lines and high resistance on wild genotypes (51.7% of the tested lines were resistant). Isolates from wild emmer elicited reciprocal disease responses: high resistance of domesticated germplasm and high susceptibility of the wild material (their original host). Analysis of variance of the quantitative phenotypic responses showed a significant Isolates × Host species interaction [ P (F) < 0.0001] and further supported these findings. Furthermore, analysis of the range of disease severity values showed that when the group of host genotypes was inoculated with Bgt isolate from the reciprocal host, coefficient of variation was significantly higher than when inoculated with its own isolates. This trend was attributed to the role of major resistance genes in the latter scenario (high proportion of complete resistance). By

Reciprocal Hosts' Responses to Powdery Mildew Isolates Originating from Domesticated Wheats and Their Wild Progenitor

Directory of Open Access Journals (Sweden)

Roi Ben-David

2018-02-01

Full Text Available The biotroph wheat powdery mildew, Blumeria graminis (DC. E.O. Speer, f. sp. tritici Em. Marchal (Bgt, has undergone long and dynamic co-evolution with its hosts. In the last 10,000 years, processes involved in plant evolution under domestication, altered host-population structure. Recently both virulence and genomic profiling separated Bgt into two groups based on their origin from domestic host and from wild emmer wheat. While most studies focused on the Bgt pathogen, there is significant knowledge gaps in the role of wheat host diversity in this specification. This study aimed to fill this gap by exploring qualitatively and also quantitatively the disease response of diverse host panel to powdery mildew [105 domesticated wheat genotypes (Triticum turgidum ssp. dicoccum, T. turgidum ssp. durum, and T. aestivum and 241 accessions of its direct progenitor, wild emmer wheat (T. turgidum ssp. dicoccoides]. A set of eight Bgt isolates, originally collected from domesticated and wild wheat was used for screening this wheat collection. The isolates from domesticated wheat elicited susceptible to moderate plant responses on domesticated wheat lines and high resistance on wild genotypes (51.7% of the tested lines were resistant. Isolates from wild emmer elicited reciprocal disease responses: high resistance of domesticated germplasm and high susceptibility of the wild material (their original host. Analysis of variance of the quantitative phenotypic responses showed a significant Isolates × Host species interaction [P(F < 0.0001] and further supported these findings. Furthermore, analysis of the range of disease severity values showed that when the group of host genotypes was inoculated with Bgt isolate from the reciprocal host, coefficient of variation was significantly higher than when inoculated with its own isolates. This trend was attributed to the role of major resistance genes in the latter scenario (high proportion of complete resistance. By

Molecular crosstalks in Leishmania-sandfly-host relationships

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Volf P.

2008-09-01

Full Text Available Sandflies (Diptera: Phlebotominae are vectors of Leishmania parasites, causative agents of important human and animal diseases with diverse manifestations. This review summarizes present knowledge about the vectorial part of Leishmania life cycle and parasite transmission to the vertebrate host. Particularly, it focuses on molecules that determine the establishment of parasite infection in sandfly midgut. It describes the concept of specific versus permissive sandfly vectors, explains the epidemiological consequences of broad susceptibility of permissive sandflies and demonstrates that genetic exchange may positively affect Leishmania fitness in the vector. Last but not least, the review describes recent knowledge about circulating antibodies produced by hosts in response to sandfly bites. Studies on specificity and kinetics of antibody response revealed that anti-saliva IgG could be used as a marker of host exposure to sandflies, i.e. as a useful tool for evaluation of vector control.

Susceptibility to Phytophthora ramorum in California bay laurel, a key foliar host of sudden oak death

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Brian L. Anacker; Nathan E. Rank; Daniel Hüberli; Matteo Garbelotto; Sarah Gordon; Rich Whitkus; Tami Harnik; Matthew Meshriy; Lori Miles; Ross K. Meentemeyer

2008-01-01

Sudden oak death, caused by the water mold Phytophthora ramorum, is a plant disease responsible for the death of hundreds of thousands of oak and tanoak trees. Some foliar hosts play a major role in the epidemiology of this disease. Upon infection by P. ramorum, these foliar hosts express non-fatal leaf lesions from which large...

Pseudomonas sax genes overcome aliphatic isothiocyanate-mediated non-host resistance in Arabidopsis

Science.gov (United States)

Jun Fan; Casey Crooks; Gary Creissen; Lionel Hill; Shirley Fairhurst; Peter Doerner; Chris Lamb

2011-01-01

Most plant-microbe interactions do not result in disease; natural products restrict non-host pathogens. We found that sulforaphane (4-methylsulfinylbutyl isothiocyanate), a natural product derived from aliphatic glucosinolates, inhibits growth in Arabidopsis of non-host Pseudomonas bacteria in planta. Multiple sax genes (saxCAB/F/D/G) were identified in Pseudomonas...

Non-Steroidal Anti-inflammatory Drugs As Host-Directed Therapy for Tuberculosis : A Systematic Review

NARCIS (Netherlands)

Kroesen, Vera M.; Gröschel, Matthias I.; Martinson, Neil; Zumla, Alimuddin; Maeurer, Markus; van der Werf, Tjip S.; Vilaplana, Cristina

2017-01-01

Lengthy, antimicrobial therapy targeting the pathogen is the mainstay of conventional tuberculosis treatment, complicated by emerging drug resistances. Host-directed therapies, including non-steroidal anti-inflammatory drugs (NSAIDs), in contrast, target host factors to mitigate disease severity. In

Fatal disease and demographic Allee effect: population persistence and extinction.

Science.gov (United States)

Friedman, Avner; Yakubu, Abdul-Aziz

2012-01-01

If a healthy stable host population at the disease-free equilibrium is subject to the Allee effect, can a small number of infected individuals with a fatal disease cause the host population to go extinct? That is, does the Allee effect matter at high densities? To answer this question, we use a susceptible-infected epidemic model to obtain model parameters that lead to host population persistence (with or without infected individuals) and to host extinction. We prove that the presence of an Allee effect in host demographics matters even at large population densities. We show that a small perturbation to the disease-free equilibrium can eventually lead to host population extinction. In addition, we prove that additional deaths due to a fatal infectious disease effectively increase the Allee threshold of the host population demographics.

Corals hosting symbiotic hydrozoans are less susceptible to predation and disease

KAUST Repository

Montano, Simone; Fattorini, Simone; Parravicini, Valeriano; Berumen, Michael L.; Galli, Paolo; Maggioni, Davide; Arrigoni, Roberto; Seveso, Davide; Strona, Giovanni

2017-01-01

for our understanding of the ecology of coral reefs, and for their conservation in the current scenario of global change, because it suggests that symbiotic hydrozoans may play an active role in protecting their scleractinian hosts from stresses induced

Histophilus somni biofilm formation in cardiopulmonary tissue of the bovine host following respiratory challenge

DEFF Research Database (Denmark)

Sandal, Indra; Shao, Jian Q.; Annadata, Satish

2009-01-01

Biofilms form in a variety of host sites following infection with many bacterial species. However, the study of biofilms in a host is hindered due to the lack of protocols for the proper experimental investigation of biofilms in vivo. Histophilus somni is an agent of respiratory and systemic...... diseases in bovines, and readily forms biofilms in vitro. In the present study the capability of H. somni to form biofilms in cardiopulmonary tissue following experimental respiratory infection in the bovine host was examined by light microscopy, transmission electron microscopy, immunoelectron microscopy...... haemagglutinin (FHA), predicted to be involved in attachment. Thus, this investigation demonstrated that H. somni is capable of forming a biofilm in its natural host, that such a biofilm may be capable of harboring other bovine respiratory disease pathogens, and that the genes responsible for biofilm formation...

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

Host genetic background impacts disease outcome during intrauterine infection with Ureaplasma parvum.

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Maria von Chamier

Full Text Available Ureaplasma parvum, an opportunistic pathogen of the human urogenital tract, has been implicated in contributing to chorioamnionitis, fetal morbidity, and fetal mortality. It has been proposed that the host genetic background is a critical factor in adverse pregnancy outcome as sequela to U. parvum intra-amniotic infection. To test this hypothesis we assessed the impact of intrauterine U. parvum infection in the prototypical TH1/M1 C57BL/6 and TH2/M2 BALB/c mouse strain. Sterile medium or U. parvum was inoculated into each uterine horn and animals were evaluated for intra-amniotic infection, fetal infection, chorioamnionitis and fetal pathology at 72 hours post-inoculation. Disease outcome was assessed by microbial culture, in situ detection of U. parvum in fetal and utero-placental tissues, grading of chorioamnionitis, and placental gene expression of IL-1α, IL-1β, IL-6, TNF-α, S100A8, and S100A9. Placental infection and colonization rates were equivalent in both strains. The in situ distribution of U. parvum in placental tissues was also similar. However, a significantly greater proportion of BALB/c fetuses were infected (P<0.02. C57BL/6 infected animals predominantly exhibited mild to moderate chorioamnionitis (P<0.0001, and a significant reduction in placental expression of IL-1α, IL-1β, IL-6, TNF-α, S100A8, and S100A9 compared to sham controls (P<0.02. Conversely, severe protracted chorioamnionitis with cellular necrosis was the predominant lesion phenotype in BALB/c mice, which also exhibited a significant increase in placental expression of IL-1α, IL-1β, IL-6, TNF-α, S100A8, and S100A9 (P<0.01. Fetal pathology in BALB/c was multi-organ and included brain, lung, heart, liver, and intestine, whereas fetal pathology in C57BL/6 was only detected in the liver and intestines. These results confirm that the host genetic background is a major determinant in ureaplasmal induced chorioamnionitis with fetal infection and fetal inflammatory

Vorinostat plus tacrolimus and mycophenolate to prevent graft-versus-host disease after related-donor reduced-intensity conditioning allogeneic haemopoietic stem-cell transplantation: a phase 1/2 trial

NARCIS (Netherlands)

Choi, S.W.; Braun, T.; Chang, L.; Ferrara, J.L.; Pawarode, A.; Magenau, J.M.; Hou, G.; Beumer, J.H.; Levine, J.E.; Goldstein, S.; Couriel, D.R.; Stockerl-Goldstein, K.; Krijanovski, O.I.; Kitko, C.; Yanik, G.A.; Lehmann, M.H.; Tawara, I.; Sun, Y; Paczesny, S.; Mapara, M.Y.; Dinarello, C.A.; Dipersio, J.F.; Reddy, P.

2014-01-01

BACKGROUND: Acute graft-versus-host disease (GVHD) remains a barrier to more widespread application of allogeneic haemopoietic stem-cell transplantation. Vorinostat is an inhibitor of histone deacetylases and was shown to attenuate GVHD in preclinical models. We aimed to study the safety and

Disentangling the influence of parasite genotype, host genotype and maternal environment on different stages of bacterial infection in Daphnia magna.

Science.gov (United States)

Hall, Matthew D; Ebert, Dieter

2012-08-22

Individuals naturally vary in the severity of infectious disease when exposed to a parasite. Dissecting this variation into genetic and environmental components can reveal whether or not this variation depends on the host genotype, parasite genotype or a range of environmental conditions. Complicating this task, however, is that the symptoms of disease result from the combined effect of a series of events, from the initial encounter between a host and parasite, through to the activation of the host immune system and the exploitation of host resources. Here, we use the crustacean Daphnia magna and its parasite Pasteuria ramosa to show how disentangling genetic and environmental factors at different stages of infection improves our understanding of the processes shaping infectious disease. Using compatible host-parasite combinations, we experimentally exclude variation in the ability of a parasite to penetrate the host, from measures of parasite clearance, the reduction in host fecundity and the proliferation of the parasite. We show how parasite resistance consists of two components that vary in environmental sensitivity, how the maternal environment influences all measured aspects of the within-host infection process and how host-parasite interactions following the penetration of the parasite into the host have a distinct temporal component.

Modulation of Host Learning in Aedes aegypti Mosquitoes.

Science.gov (United States)

Vinauger, Clément; Lahondère, Chloé; Wolff, Gabriella H; Locke, Lauren T; Liaw, Jessica E; Parrish, Jay Z; Akbari, Omar S; Dickinson, Michael H; Riffell, Jeffrey A

2018-02-05

How mosquitoes determine which individuals to bite has important epidemiological consequences. This choice is not random; most mosquitoes specialize in one or a few vertebrate host species, and some individuals in a host population are preferred over others. Mosquitoes will also blood feed from other hosts when their preferred is no longer abundant, but the mechanisms mediating these shifts between hosts, and preferences for certain individuals within a host species, remain unclear. Here, we show that olfactory learning may contribute to Aedes aegypti mosquito biting preferences and host shifts. Training and testing to scents of humans and other host species showed that mosquitoes can aversively learn the scent of specific humans and single odorants and learn to avoid the scent of rats (but not chickens). Using pharmacological interventions, RNAi, and CRISPR gene editing, we found that modification of the dopamine-1 receptor suppressed their learning abilities. We further show through combined electrophysiological and behavioral recordings from tethered flying mosquitoes that these odors evoke changes in both behavior and antennal lobe (AL) neuronal responses and that dopamine strongly modulates odor-evoked responses in AL neurons. Not only do these results provide direct experimental evidence that olfactory learning in mosquitoes can play an epidemiological role, but collectively, they also provide neuroanatomical and functional demonstration of the role of dopamine in mediating this learning-induced plasticity, for the first time in a disease vector insect. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mosquito host choices on livestock amplifiers of Rift Valley fever virus in Kenya

Science.gov (United States)

Animal hosts may vary in their attraction and acceptability as components of the host location process for assessing biting rates of vectors and risk of exposure to pathogens. However, these parameters remain poorly understood for mosquito vectors of the Rift Valley fever (RVF), an arboviral disease...

MicroRNAs in the host response to viral infections of veterinary importance

Directory of Open Access Journals (Sweden)

Mohamed Samir Ahmed

2016-10-01

Full Text Available The discovery of small regulatory non-coding RNAs has been an exciting advance in the field of genomics. MicroRNAs (miRNAs are endogenous RNA molecules, approximately 22 nucleotides in length that regulate gene expression, mostly at the post-transcriptional level. MiRNA profiling technologies have made it possible to identify and quantify novel miRNAs and to study their regulation and potential roles in disease pathogenesis. Although miRNAs have been extensively investigated in viral infections of humans, their implications in viral diseases affecting animals of veterinary importance are much less understood. The number of annotated miRNAs in different animal species is growing continuously, and novel roles in regulating host-pathogen interactions are being discovered, for instance miRNA-mediated augmentation of viral transcription and replication. In this review, we present an overview of synthesis and function of miRNAs and an update on the current state of research on host-encoded miRNAs in the genesis of viral infectious diseases in their natural animal host as well as in selected in vivo and in vitro laboratory models.

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.

Nesting bird "host funnel" increases mosquito-bird contact rate.

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Caillouët, Kevin A; Riggan, Anna E; Bulluck, Lesley P; Carlson, John C; Sabo, Roy T

2013-03-01

Increases in vector-host contact rates can enhance arbovirus transmission intensity. We investigated weekly fluctuations in contact rates between mosquitoes and nesting birds using the recently described Nest Mosquito Trap (NMT). The number of mosquitoes per nestling increased from nesting season. Our evidence suggests the coincidence of the end of the avian nesting season and increasing mosquito abundances may have caused a "host funnel," concentrating host-seeking mosquitoes to the few remaining nestlings. The relative abundance of mosquitoes collected by the NMT suggests that significantly more Aedes albopictus (Skuse) and Culex pipiens (L.) /restuans (Theobald) sought nesting bird bloodmeals than were predicted by their relative abundances in CO2-baited Centers for Disease Control and Prevention light and gravid traps. Culex salinarius (Coquillett) and Culex erraticus Dyar and Knab were collected in NMTs in proportion to their relative abundances in the generic traps. Temporal host funnels and nesting bird host specificity may enhance arbovirus amplification and explain observed West Nile virus and St. Louis encephalitis virus amplification periods.

Associate host in single-layer co-host polymer electrophosphorescent devices

International Nuclear Information System (INIS)

Wang Yuanmin; Teng Feng; Feng Bin; Wang Yongsheng; Xu Xurong

2006-01-01

The definition and role of 'host' in polymer LED materials are studied in the present work. 'Primary host' and 'associate host' have been proposed and the rules of how to select an associate host are reported. Based on our experiments and the analysis of the energy scheme of the devices, we suggest that the values of the lowest unoccupied molecular orbital (LUMO) and highest occupied molecular orbital (HOMO) are critical determinant in selecting a suitable associate host. On one hand, the associate host should be a hole-blocking material. This can confine the excitons in the active layer. On the other hand, the associate host should have a suitable LUMO that is convenient for electrons to transport

Epigenetics of host-pathogen interactions: the road ahead and the road behind.

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Elena Gómez-Díaz

Full Text Available A growing body of evidence points towards epigenetic mechanisms being responsible for a wide range of biological phenomena, from the plasticity of plant growth and development to the nutritional control of caste determination in honeybees and the etiology of human disease (e.g., cancer. With the (partial elucidation of the molecular basis of epigenetic variation and the heritability of certain of these changes, the field of evolutionary epigenetics is flourishing. Despite this, the role of epigenetics in shaping host-pathogen interactions has received comparatively little attention. Yet there is plenty of evidence supporting the implication of epigenetic mechanisms in the modulation of the biological interaction between hosts and pathogens. The phenotypic plasticity of many key parasite life-history traits appears to be under epigenetic control. Moreover, pathogen-induced effects in host phenotype may have transgenerational consequences, and the bases of these changes and their heritability probably have an epigenetic component. The significance of epigenetic modifications may, however, go beyond providing a mechanistic basis for host and pathogen plasticity. Epigenetic epidemiology has recently emerged as a promising area for future research on infectious diseases. In addition, the incorporation of epigenetic inheritance and epigenetic plasticity mechanisms to evolutionary models and empirical studies of host-pathogen interactions will provide new insights into the evolution and coevolution of these associations. Here, we review the evidence available for the role epigenetics on host-pathogen interactions, and the utility and versatility of the epigenetic technologies available that can be cross-applied to host-pathogen studies. We conclude with recommendations and directions for future research on the burgeoning field of epigenetics as applied to host-pathogen interactions.

Host-selective toxins of Pyrenophora tritici-repentis induce common responses associated with host susceptibility.

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Iovanna Pandelova

Full Text Available Pyrenophora tritici-repentis (Ptr, a necrotrophic fungus and the causal agent of tan spot of wheat, produces one or a combination of host-selective toxins (HSTs necessary for disease development. The two most studied toxins produced by Ptr, Ptr ToxA (ToxA and Ptr ToxB (ToxB, are proteins that cause necrotic or chlorotic symptoms respectively. Investigation of host responses induced by HSTs provides better insight into the nature of the host susceptibility. Microarray analysis of ToxA has provided evidence that it can elicit responses similar to those associated with defense. In order to evaluate whether there are consistent host responses associated with susceptibility, a similar analysis of ToxB-induced changes in the same sensitive cultivar was conducted. Comparative analysis of ToxA- and ToxB-induced transcriptional changes showed that similar groups of genes encoding WRKY transcription factors, RLKs, PRs, components of the phenylpropanoid and jasmonic acid pathways are activated. ROS accumulation and photosystem dysfunction proved to be common mechanism-of-action for these toxins. Despite similarities in defense responses, transcriptional and biochemical responses as well as symptom development occur more rapidly for ToxA compared to ToxB, which could be explained by differences in perception as well as by differences in activation of a specific process, for example, ethylene biosynthesis in ToxA treatment. Results of this study suggest that perception of HSTs will result in activation of defense responses as part of a susceptible interaction and further supports the hypothesis that necrotrophic fungi exploit defense responses in order to induce cell death.

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.

The Host-Agent-Environment Concept of Accidents.

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Phillips, Don

Background information is presented to indicate that accidents are an environmental health problem. While accidents are seldom thought to be a disease process, in many ways there are remarkable similarities--not only in terms of causal relationships, but also in preventive aspects. These parallels are described in terms of host-agent-environment…

Deer density and disease prevalence influence transmission of Chronic Wasting Disease in White-tailed Deer

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Samuel, Michael D.; Richards, Bryan J.; Storm, Daniel J.; Rolley, Robert E.; Shelton, Paul; Nicholas S. Keuler,; Timothy R. Van Deelen,

2013-01-01

Host-parasite dynamics and strategies for managing infectious diseases of wildlife depend on the functional relationship between disease transmission rates and host density. However, the disease transmission function is rarely known for free-living wildlife, leading to uncertainty regarding the impacts of diseases on host populations and effective control actions. We evaluated the influence of deer density, landscape features, and soil clay content on transmission of chronic wasting disease (CWD) in young (disease prevalence and density of infected deer, performed better than simple density- and frequency-dependent models. Our results indicate a combination of social structure, non-linear relationships between infectious contact and deer density, and distribution of disease among groups are important factors driving CWD infection in young deer. The landscape covariates % deciduous forest cover and forest edge density also were positively associated with infection rates, but soil clay content had no measurable influences on CWD transmission. Lack of strong density-dependent transmission rates indicates that controlling CWD by reducing deer density will be difficult. The consequences of non-linear disease transmission and aggregation of disease on cervid populations deserves further consideration.

Chronic graft-versus-host disease: long-term results from a randomized trial on graft-versus-host disease prophylaxis with or without anti-T-cell globulin ATG-Fresenius.

Science.gov (United States)

Socié, Gérard; Schmoor, Claudia; Bethge, Wolfgang A; Ottinger, Hellmut D; Stelljes, Matthias; Zander, Axel R; Volin, Liisa; Ruutu, Tapani; Heim, Dominik A; Schwerdtfeger, Rainer; Kolbe, Karin; Mayer, Jiri; Maertens, Johan A; Linkesch, Werner; Holler, Ernst; Koza, Vladimir; Bornhäuser, Martin; Einsele, Hermann; Kolb, Hans-Jochem; Bertz, Hartmut; Egger, Matthias; Grishina, Olga; Finke, Jürgen

2011-06-09

Previous randomized graft-versus-host disease (GVHD)-prophylaxis trials have failed to demonstrate reduced incidence and severity of chronic GVHD (cGVHD). Here we reanalyzed and updated a randomized phase 3 trial comparing standard GVHD prophylaxis with or without pretransplantation ATG-Fresenius (ATG-F) in 201 adult patients receiving myeloablative conditioning before transplantation from unrelated donors. The cumulative incidence of extensive cGVHD after 3 years was 12.2% in the ATG-F group versus 45.0% in the control group (P < .0001). The 3-year cumulative incidence of relapse and of nonrelapse mortality was 32.6% and 19.4% in the ATG-F group and 28.2% and 33.5% in the control group (hazard ratio [HR] = 1.21, P = .47, and HR = 0.68, P = .18), respectively. This nonsignificant reduction in nonrelapse mortality without increased relapse risk led to an overall survival rate after 3 years of 55.2% in the ATG-F group and 43.3% in the control group (HR = 0.84, P = .39, nonsignificant). The HR for receiving immunosuppressive therapy (IST) was 0.31 after ATG-F (P < .0001), and the 3-year probability of survival free of IST was 52.9% and 16.9% in the ATG-F versus control, respectively. The addition of ATG-F to standard cyclosporine, methotrexate GVHD prophylaxis lowers the incidence and severity of cGVHD, and the risk of receiving IST without raising the relapse rate. ATG-F prophylaxis reduces cGVHD morbidity.

Host-detrimental role of Esx-1-mediated inflammasome activation in mycobacterial infection.

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Fredric Carlsson

2010-05-01

Full Text Available The Esx-1 (type VII secretion system is a major virulence determinant of pathogenic mycobacteria, including Mycobacterium marinum. However, the molecular events and host-pathogen interactions underlying Esx-1-mediated virulence in vivo remain unclear. Here we address this problem in a non-lethal mouse model of M. marinum infection that allows detailed quantitative analysis of disease progression. M. marinum established local infection in mouse tails, with Esx-1-dependent formation of caseating granulomas similar to those formed in human tuberculosis, and bone deterioration reminiscent of skeletal tuberculosis. Analysis of tails infected with wild type or Esx-1-deficient bacteria showed that Esx-1 enhanced generation of proinflammatory cytokines, including the secreted form of IL-1beta, suggesting that Esx-1 promotes inflammasome activation in vivo. In vitro experiments indicated that Esx-1-dependent inflammasome activation required the host NLRP3 and ASC proteins. Infection of wild type and ASC-deficient mice demonstrated that Esx-1-dependent inflammasome activation exacerbated disease without restricting bacterial growth, indicating a host-detrimental role of this inflammatory pathway in mycobacterial infection. These findings define an immunoregulatory role for Esx-1 in a specific host-pathogen interaction in vivo, and indicate that the Esx-1 secretion system promotes disease and inflammation through its ability to activate the inflammasome.

Perspectives on the Trypanosoma cruzi–host cell receptor interactions

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Villalta, Fernando; Scharfstein, Julio; Ashton, Anthony W.; Tyler, Kevin M.; Guan, Fangxia; Mukherjee, Shankar; Lima, Maria F.; Alvarez, Sandra; Weiss, Louis M.; Huang, Huan; Machado, Fabiana S.

2009-01-01

Chagas disease is caused by the parasite Trypanosoma cruzi. The critical initial event is the interaction of the trypomastigote form of the parasite with host receptors. This review highlights recent observations concerning these interactions. Some of the key receptors considered are those for thromboxane, bradykinin, and for the nerve growth factor TrKA. Other important receptors such as galectin-3, thrombospondin, and laminin are also discussed. Investigation into the molecular biology and cell biology of host receptors for T. cruzi may provide novel therapeutic targets. PMID:19283409

Spatial heterogeneity, frequency-dependent selection and polymorphism in host-parasite interactions

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Tellier Aurélien

2011-11-01

Full Text Available Abstract Background Genomic and pathology analysis has revealed enormous diversity in genes involved in disease, including those encoding host resistance and parasite effectors (also known in plant pathology as avirulence genes. It has been proposed that such variation may persist when an organism exists in a spatially structured metapopulation, following the geographic mosaic of coevolution. Here, we study gene-for-gene relationships governing the outcome of plant-parasite interactions in a spatially structured system and, in particular, investigate the population genetic processes which maintain balanced polymorphism in both species. Results Following previous theory on the effect of heterogeneous environments on maintenance of polymorphism, we analysed a model with two demes in which the demes have different environments and are coupled by gene flow. Environmental variation is manifested by different coefficients of natural selection, the costs to the host of resistance and to the parasite of virulence, the cost to the host of being diseased and the cost to an avirulent parasite of unsuccessfully attacking a resistant host. We show that migration generates negative direct frequency-dependent selection, a condition for maintenance of stable polymorphism in each deme. Balanced polymorphism occurs preferentially if there is heterogeneity for costs of resistance and virulence alleles among populations and to a lesser extent if there is variation in the cost to the host of being diseased. We show that the four fitness costs control the natural frequency of oscillation of host resistance and parasite avirulence alleles. If demes have different costs, their frequencies of oscillation differ and when coupled by gene flow, there is amplitude death of the oscillations in each deme. Numerical simulations show that for a multiple deme island model, costs of resistance and virulence need not to be present in each deme for stable polymorphism to occur

Salt, chloride, bleach, and innate host defense

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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

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.

Diversity in Betasatellites Associated with Cotton Leaf Curl Disease During Source-To-Sink Movement Through a Resistant Host

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Iftikhar Ali Khan

2016-02-01

Full Text Available Cotton leaf curl is devastating disease of cotton characterized by leaf curling, vein darkening and enations. The disease symptoms are induced by DNA satellite known as Cotton leaf curl Multan betasatellite (CLCuMuB, dominant betasatellite in cotton but another betasatellite known as Chili leaf curl betasatellite (ChLCB is also found associated with the disease. Grafting experiment was performed to determine if host plant resistance is determinant of dominant population of betasatellite in cotton (several distinct strains of CLCuMuB are associated with the disease. Infected scion of Gossypium hirsutum collected from field (the source was grafted on G. arboreum, a diploid cotton species, resistant to the disease. A healthy scion of G. hirsutum (sink was grafted at the top of G. arboreum to determine the movement of virus/betasatellite to upper susceptible scion of G. hirsutum. Symptoms of disease appeared in the upper scion and presence of virus/betasatellite in the upper scion was confirmed via molecular techniques, showing that virus/betasatellite was able to move to upper scion through resistant G. arboreum. However, no symptoms appeared on G. arboreum. Betasatelites were cloned and sequenced from lower scion, upper scion and G. arboreum which show that the lower scion contained both CLCuMuB and ChLCB, however only ChLCB was found in G. arboreum. The upper scion contained CLCuMuB with a deletion of 78 nucleotides (nt in the non-coding region between A-rich sequence and βC1 gene and insertion of 27 nt in the middle of βC1 ORF. This study may help in investigating molecular basis of resistance in G. arboreum.

Host Range Specificity in Verticillium dahliae.

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Bhat, R G; Subbarao, K V

1999-12-01

ABSTRACT Verticillium dahliae isolates from artichoke, bell pepper, cabbage, cauliflower, chili pepper, cotton, eggplant, lettuce, mint, potato, strawberry, tomato, and watermelon and V. albo-atrum from alfalfa were evaluated for their pathogenicity on all 14 hosts. One-month-old seedlings were inoculated with a spore suspension of about 10(7) conidia per ml using a root-dip technique and incubated in the greenhouse. Disease incidence and severity, plant height, and root and shoot dry weights were recorded 6 weeks after inoculation. Bell pepper, cabbage, cauliflower, cotton, eggplant, and mint isolates exhibited host specificity and differential pathogenicity on other hosts, whereas isolates from artichoke, lettuce, potato, strawberry, tomato, and watermelon did not. Bell pepper was resistant to all Verticillium isolates except isolates from bell pepper and eggplant. Thus, host specificity exists in some isolates of V. dahliae. The same isolates were characterized for vegetative compatibility groups (VCGs) through complementation of nitrate nonutilizing (nit) mutants. Cabbage and cauliflower isolates did not produce nit mutants. The isolate from cotton belonged to VCG 1; isolates from bell pepper, eggplant, potato, and tomato, to VCG 4; and the remaining isolates, to VCG 2. These isolates were also analyzed using the random amplified polymorphic DNA (RAPD) method. Forty random primers were screened, and eighteen of them amplified DNA from Verticillium. Based on RAPD banding patterns, cabbage and cauliflower isolates formed a unique group, distinct from other V. dahliae and V. albo-atrum groups. Minor genetic variations were observed among V. dahliae isolates from other hosts, regardless of whether they were host specific or not. There was no correlation among pathogenicity, VCGs, and RAPD banding patterns. Even though the isolates belonged to different VCGs, they shared similar RAPD profiles. These results suggest that management of Verticillium wilt in some crops

Host-Microbe Interactions in Microgravity: Assessment and Implications

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Jamie S. Foster

2014-05-01

Full Text Available Spaceflight imposes several unique stresses on biological life that together can have a profound impact on the homeostasis between eukaryotes and their associated microbes. One such stressor, microgravity, has been shown to alter host-microbe interactions at the genetic and physiological levels. Recent sequencing of the microbiomes associated with plants and animals have shown that these interactions are essential for maintaining host health through the regulation of several metabolic and immune responses. Disruptions to various environmental parameters or community characteristics may impact the resiliency of the microbiome, thus potentially driving host-microbe associations towards disease. In this review, we discuss our current understanding of host-microbe interactions in microgravity and assess the impact of this unique environmental stress on the normal physiological and genetic responses of both pathogenic and mutualistic associations. As humans move beyond our biosphere and undergo longer duration space flights, it will be essential to more fully understand microbial fitness in microgravity conditions in order to maintain a healthy homeostasis between humans, plants and their respective microbiomes.

Host-microbe interactions in microgravity: assessment and implications.

Science.gov (United States)

Foster, Jamie S; Wheeler, Raymond M; Pamphile, Regine

2014-05-26

Spaceflight imposes several unique stresses on biological life that together can have a profound impact on the homeostasis between eukaryotes and their associated microbes. One such stressor, microgravity, has been shown to alter host-microbe interactions at the genetic and physiological levels. Recent sequencing of the microbiomes associated with plants and animals have shown that these interactions are essential for maintaining host health through the regulation of several metabolic and immune responses. Disruptions to various environmental parameters or community characteristics may impact the resiliency of the microbiome, thus potentially driving host-microbe associations towards disease. In this review, we discuss our current understanding of host-microbe interactions in microgravity and assess the impact of this unique environmental stress on the normal physiological and genetic responses of both pathogenic and mutualistic associations. As humans move beyond our biosphere and undergo longer duration space flights, it will be essential to more fully understand microbial fitness in microgravity conditions in order to maintain a healthy homeostasis between humans, plants and their respective microbiomes.

Seven challenges for modelling indirect transmission: Vector-borne diseases, macroparasites and neglected tropical diseases

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T. Déirdre Hollingsworth

2015-03-01

Full Text Available Many of the challenges which face modellers of directly transmitted pathogens also arise when modelling the epidemiology of pathogens with indirect transmission – whether through environmental stages, vectors, intermediate hosts or multiple hosts. In particular, understanding the roles of different hosts, how to measure contact and infection patterns, heterogeneities in contact rates, and the dynamics close to elimination are all relevant challenges, regardless of the mode of transmission. However, there remain a number of challenges that are specific and unique to modelling vector-borne diseases and macroparasites. Moreover, many of the neglected tropical diseases which are currently targeted for control and elimination are vector-borne, macroparasitic, or both, and so this article includes challenges which will assist in accelerating the control of these high-burden diseases. Here, we discuss the challenges of indirect measures of infection in humans, whether through vectors or transmission life stages and in estimating the contribution of different host groups to transmission. We also discuss the issues of “evolution-proof” interventions against vector-borne disease.

Seven challenges for modelling indirect transmission: vector-borne diseases, macroparasites and neglected tropical diseases.

Science.gov (United States)

Hollingsworth, T Déirdre; Pulliam, Juliet R C; Funk, Sebastian; Truscott, James E; Isham, Valerie; Lloyd, Alun L

2015-03-01

Many of the challenges which face modellers of directly transmitted pathogens also arise when modelling the epidemiology of pathogens with indirect transmission--whether through environmental stages, vectors, intermediate hosts or multiple hosts. In particular, understanding the roles of different hosts, how to measure contact and infection patterns, heterogeneities in contact rates, and the dynamics close to elimination are all relevant challenges, regardless of the mode of transmission. However, there remain a number of challenges that are specific and unique to modelling vector-borne diseases and macroparasites. Moreover, many of the neglected tropical diseases which are currently targeted for control and elimination are vector-borne, macroparasitic, or both, and so this article includes challenges which will assist in accelerating the control of these high-burden diseases. Here, we discuss the challenges of indirect measures of infection in humans, whether through vectors or transmission life stages and in estimating the contribution of different host groups to transmission. We also discuss the issues of "evolution-proof" interventions against vector-borne disease. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Staphylococcal Superantigens Spark Host-Mediated Danger Signals

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Terry eKrakauer

2016-02-01

Full Text Available Staphylococcal enterotoxin B (SEB of Staphylococcus aureus, and related superantigenic toxins produced by myriad microbes, are potent stimulators of the immune system causing a variety of human diseases from transient food poisoning to lethal toxic shock. These protein toxins bind directly to specific V regions of T-cell receptors (TCR and major histocompatibility complex (MHC class II on antigen-presenting cells, resulting in hyperactivation of T lymphocytes and monocytes / macrophages. Activated host cells produce excessive amounts of proinflammatory cytokines and chemokines, especially tumor necrosis factor α, interleukin 1 (IL-1, IL-2, interferon γ (IFNγ, and macrophage chemoattractant protein 1 causing clinical symptoms of fever, hypotension, and shock. Because of superantigen-induced T cells skewed towards TH1 helper cells, and the induction of proinflammatory cytokines, superantigens can exacerbate autoimmune diseases. Upon TCR / MHC ligation, pathways induced by superantigens include the mitogen-activated protein kinase cascades and cytokine receptor signaling, resulting in activation of NFκB and the phosphoinositide 3-kinase / mammalian target of rapamycin pathways. Various mouse models exist to study SEB-induced shock including those with potentiating agents, transgenic mice and an SEB-only model. However, therapeutics to treat toxic shock remain elusive as host response genes central to pathogenesis of superantigens have only been identified recently. Gene profiling of a murine model for SEB-induced shock reveals novel molecules upregulated in multiple organs not previously associated with SEB-induced responses. The pivotal genes include intracellular DNA / RNA sensors, apoptosis / DNA damage-related molecules, immunoproteasome components, as well as anti-viral and IFN-stimulated genes. The host-wide induction of these, and other, anti-microbial defense genes provide evidence that SEB elicits danger signals resulting in multi

Host-pathogen interactions in Lyme disease and their application in diagnostics

NARCIS (Netherlands)

Burgel, Nathalie Daniëlle van

2013-01-01

B. burgdorferi has a wide variety of strategies to hide from the host immune system. Complement regulatory binding proteins have been described for almost all complement resistant B. burgdorferi sl, except for the complement resistant B. bavariensis, one of the species that is known to frequently

Defecation of a colon cast as a rare presentation of acute graft-versus-host disease

International Nuclear Information System (INIS)

Al Ashgar, Hamad; Peedikayil, Musthafa; Chaudhri, Naeem; AlGhamdi, Abdulmonem

2009-01-01

Diffuse involvement of the gastrointestinal tract by graft versus host disease (GVHD) is a common complication of allogeneic hematopoietic stem cell transplant (HSCT). Gastrointestinal GVHD usually presents 3 or more weeks after HSCT and is characterized by profuse diarrhea, anorexia, nausea, vomiting, abdominal pain and gastrointestinal bleeding. We report a case of a 23 year old male who had undergone allogeneic HSCT and presented with bloody diarrhea on the 90th day post-HSCT. On the fourth day of admission, the patient passed per rectum a 27-cm long pinkish colored fleshy material recognized as a colon cast. Sigmoidoscopy showed a congested and erythematous rectum with the remaining portion of the colon cast attached to the proximal part of the sigmoid colon. A biopsy from the rectal wall was suggestive of grade 4 GVHD. The patient was treated with methylprednisolone, cyclosporine and mycophenolate mofetil, with a partial response (diarrhea and abdominal pain improved), but then he developed multiple other medical complications and died after 3 months. (author)

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

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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

Dual Action of Myricetin on Porphyromonas gingivalis and the Inflammatory Response of Host Cells: A Promising Therapeutic Molecule for Periodontal Diseases.

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Daniel Grenier

Full Text Available Periodontitis that affects the underlying structures of the periodontium, including the alveolar bone, is a multifactorial disease, whose etiology involves interactions between specific bacterial species of the subgingival biofilm and the host immune components. In the present study, we investigated the effects of myricetin, a flavonol largely distributed in fruits and vegetables, on growth and virulence properties of Porphyromonas gingivalis as well as on the P. gingivalis-induced inflammatory response in host cells. Minimal inhibitory concentration values of myricetin against P. gingivalis were in the range of 62.5 to 125 μg/ml. The iron-chelating activity of myricetin may contribute to the antibacterial activity of this flavonol. Myricetin was found to attenuate the virulence of P. gingivalis by reducing the expression of genes coding for important virulence factors, including proteinases (rgpA, rgpB, and kgp and adhesins (fimA, hagA, and hagB. Myricetin dose-dependently prevented NF-κB activation in a monocyte model. Moreover, it inhibited the secretion of IL-6, IL-8 and MMP-3 by P. gingivalis-stimulated gingival fibroblasts. In conclusion, our study brought clear evidence that the flavonol myricetin exhibits a dual action on the periodontopathogenic bacterium P. gingivalis and the inflammatory response of host cells. Therefore, myricetin holds promise as a therapeutic agent for the treatment/prevention of periodontitis.

Host-Parasite Relationship in Cystic Echinococcosis: An Evolving Story

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Siracusano, Alessandra; Delunardo, Federica; Teggi, Antonella; Ortona, Elena

2012-01-01

The larval stage of Echinococcus granulosus causes cystic echinococcosis, a neglected infectious disease that constitutes a major public health problem in developing countries. Despite being under constant barrage by the immune system, E. granulosus modulates antiparasite immune responses and persists in the human hosts with detectable humoral and cellular responses against the parasite. In vitro and in vivo immunological approaches, together with molecular biology and immunoproteomic technologies, provided us exciting insights into the mechanisms involved in the initiation of E. granulosus infection and the consequent induction and regulation of the immune response. Although the last decade has clarified many aspects of host-parasite relationship in human cystic echinococcosis, establishing the full mechanisms that cause the disease requires more studies. Here, we review some of the recent developments and discuss new avenues in this evolving story of E. granulosus infection in man. PMID:22110535

How do PrPSc Prions Spread between Host Species, and within Hosts?

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Neil A. Mabbott

2017-11-01

Full Text Available Prion diseases are sub-acute neurodegenerative diseases that affect humans and some domestic and free-ranging animals. Infectious prion agents are considered to comprise solely of abnormally folded isoforms of the cellular prion protein known as PrPSc. Pathology during prion disease is restricted to the central nervous system where it causes extensive neurodegeneration and ultimately leads to the death of the host. The first half of this review provides a thorough account of our understanding of the various ways in which PrPSc prions may spread between individuals within a population, both horizontally and vertically. Many natural prion diseases are acquired peripherally, such as by oral exposure, lesions to skin or mucous membranes, and possibly also via the nasal cavity. Following peripheral exposure, some prions accumulate to high levels within the secondary lymphoid organs as they make their journey from the site of infection to the brain, a process termed neuroinvasion. The replication of PrPSc prions within secondary lymphoid organs is important for their efficient spread to the brain. The second half of this review describes the key tissues, cells and molecules which are involved in the propagation of PrPSc prions from peripheral sites of exposure (such as the lumen of the intestine to the brain. This section also considers how additional factors such as inflammation and aging might influence prion disease susceptibility.

Sexually transmitted parasites and host mating behavior in the decorated cricket

OpenAIRE

Lien T. Luong; Harry K. Kaya

2005-01-01

Sexually transmitted diseases play a potentially important role in the ecology and evolution of host mating behavior. Here, we use a sexually transmitted nematode-cricket (Mehdinema alii--Gryllodes sigillatus) system to examine the effects of parasitism on host mating activity and female choice. Previous work has shown that infected male crickets produce a significantly smaller nuptial gift (spermatophylax) than uninfected males. This is expected to result in reduced spermatophylax feeding du...

Host Ecology Rather Than Host Phylogeny Drives Amphibian Skin Microbial Community Structure in the Biodiversity Hotspot of Madagascar

Science.gov (United States)

Bletz, Molly C.; Archer, Holly; Harris, Reid N.; McKenzie, Valerie J.; Rabemananjara, Falitiana C. E.; Rakotoarison, Andolalao; Vences, Miguel

2017-01-01

) was enriched on terrestrial frogs. The presence of shared bacterial OTUs across geographic regions for selected host genera suggests the presence of core microbial communities which in Madagascar, might be driven more strongly by a species’ preference for specific microhabitats than by the physical, physiological or biochemical properties of their skin. These results corroborate that both host and environmental factors are driving community assembly of amphibian cutaneous microbial communities, and provide an improved foundation for elucidating their role in disease resistance. PMID:28861051

Host Ecology Rather Than Host Phylogeny Drives Amphibian Skin Microbial Community Structure in the Biodiversity Hotspot of Madagascar

Directory of Open Access Journals (Sweden)

Molly C. Bletz

2017-08-01

(Rhizobiaceae was enriched on terrestrial frogs. The presence of shared bacterial OTUs across geographic regions for selected host genera suggests the presence of core microbial communities which in Madagascar, might be driven more strongly by a species’ preference for specific microhabitats than by the physical, physiological or biochemical properties of their skin. These results corroborate that both host and environmental factors are driving community assembly of amphibian cutaneous microbial communities, and provide an improved foundation for elucidating their role in disease resistance.

Host Ecology Rather Than Host Phylogeny Drives Amphibian Skin Microbial Community Structure in the Biodiversity Hotspot of Madagascar.

Science.gov (United States)

Bletz, Molly C; Archer, Holly; Harris, Reid N; McKenzie, Valerie J; Rabemananjara, Falitiana C E; Rakotoarison, Andolalao; Vences, Miguel

2017-01-01

) was enriched on terrestrial frogs. The presence of shared bacterial OTUs across geographic regions for selected host genera suggests the presence of core microbial communities which in Madagascar, might be driven more strongly by a species' preference for specific microhabitats than by the physical, physiological or biochemical properties of their skin. These results corroborate that both host and environmental factors are driving community assembly of amphibian cutaneous microbial communities, and provide an improved foundation for elucidating their role in disease resistance.

Population genetic structure of a common host predicts the spread of white-nose syndrome, an emerging infectious disease in bats.

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Wilder, Aryn P; Kunz, Thomas H; Sorenson, Michael D

2015-11-01

Landscape complexity influences patterns of animal dispersal, which in turn may affect both gene flow and the spread of pathogens. White-nose syndrome (WNS) is an introduced fungal disease that has spread rapidly throughout eastern North America, causing massive mortality in bat populations. We tested for a relationship between the population genetic structure of the most common host, the little brown myotis (Myotis lucifugus), and the geographic spread of WNS to date by evaluating logistic regression models of WNS risk among hibernating colonies in eastern North America. We hypothesized that risk of WNS to susceptible host colonies should increase with both geographic proximity and genetic similarity, reflecting historical connectivity, to infected colonies. Consistent with this hypothesis, inclusion of genetic distance between infected and susceptible colonies significantly improved models of disease spread, capturing heterogeneity in the spatial expansion of WNS despite low levels of genetic differentiation among eastern populations. Expanding our genetic analysis to the continental range of little brown myotis reveals strongly contrasting patterns of population structure between eastern and western North America. Genetic structure increases markedly moving westward into the northern Great Plains, beyond the current distribution of WNS. In western North America, genetic differentiation of geographically proximate populations often exceeds levels observed across the entire eastern region, suggesting infrequent and/or locally restricted dispersal, and thus relatively limited opportunities for pathogen introduction in western North America. Taken together, our analyses suggest a possibly slower future rate of spread of the WNS pathogen, at least as mediated by little brown myotis. © 2015 John Wiley & Sons Ltd.

Does reservoir host mortality enhance transmission of West Nile virus?

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Foppa Ivo M

2007-05-01

Full Text Available Abstract Background Since its 1999 emergence in New York City, West Nile virus (WNV has become the most important and widespread cause of mosquito-transmitted disease in North America. Its sweeping spread from the Atlantic to the Pacific coast was accompanied by widespread mortality among wild birds, especially corvids. Only sporadic avian mortality had previously been associated with this infection in the Old World. Here, we examine the possibility that reservoir host mortality may intensify transmission, both by concentrating vector mosquitoes on remaining hosts and by preventing the accumulation of "herd immunity". Results Inspection of the Ross-Macdonald expression of the basic reproductive number (R0 suggests that this quantity may increase with reservoir host mortality. Computer simulation confirms this finding and indicates that the level of virulence is positively associated with the numbers of infectious mosquitoes by the end of the epizootic. The presence of reservoir incompetent hosts in even moderate numbers largely eliminated the transmission-enhancing effect of host mortality. Local host die-off may prevent mosquitoes to "waste" infectious blood meals on immune host and may thus facilitate perpetuation and spread of transmission. Conclusion Under certain conditions, host mortality may enhance transmission of WNV and similarly maintained arboviruses and thus facilitate their emergence and spread. The validity of the assumptions upon which this argument is built need to be empirically examined.

The path to host extinction can lead to loss of generalist parasites.

Science.gov (United States)

Farrell, Maxwell J; Stephens, Patrick R; Berrang-Ford, Lea; Gittleman, John L; Davies, T Jonathan

2015-07-01

Host extinction can alter disease transmission dynamics, influence parasite extinction and ultimately change the nature of host-parasite systems. While theory predicts that single-host parasites are among the parasite species most susceptible to extinction following declines in their hosts, documented parasite extinctions are rare. Using a comparative approach, we investigate how the richness of single-host and multi-host parasites is influenced by extinction risk among ungulate and carnivore hosts. Host-parasite associations for free-living carnivores (order Carnivora) and terrestrial ungulates (orders Perissodactyla + Cetartiodactyla minus cetaceans) were merged with host trait data and IUCN Red List status to explore the distribution of single-host and multi-host parasites among threatened and non-threatened hosts. We find that threatened ungulates harbour a higher proportion of single-host parasites compared to non-threatened ungulates, which is explained by decreases in the richness of multi-host parasites. However, among carnivores threat status is not a significant predictor of the proportion of single-host parasites, or the richness of single-host or multi-host parasites. The loss of multi-host parasites from threatened ungulates may be explained by decreased cross-species contact as hosts decline and habitats become fragmented. Among carnivores, threat status may not be important in predicting patterns of parasite specificity because host decline results in equal losses of both single-host parasites and multi-host parasites through reduction in average population density and frequency of cross-species contact. Our results contrast with current models of parasite coextinction and highlight the need for updated theories that are applicable across host groups and account for both inter- and intraspecific contact. © 2015 The Authors. Journal of Animal Ecology © 2015 British Ecological Society.

Interface Molecules of Angiostrongylus cantonensis: Their Role in Parasite Survival and Modulation of Host Defenses