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Secreted proteins from the helminth Fasciola hepatica inhibit the initiation of autoreactive T cell responses and prevent diabetes in the NOD mouse

Lund, Maria E ; O'Brien, Bronwyn A ; Hutchinson, Andrew T ; Robinson, Mark W ; Simpson, Ann M ; Dalton, John P ; Donnelly, Sheila Chatenoud, Lucienne

PloS one, 2014-01, Vol.9 (1), p.e86289-e86289 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Secreted proteins from the helminth Fasciola hepatica inhibit the initiation of autoreactive T cell responses and prevent diabetes in the NOD mouse
Autor: Lund, Maria E ; O'Brien, Bronwyn A ; Hutchinson, Andrew T ; Robinson, Mark W ; Simpson, Ann M ; Dalton, John P ; Donnelly, Sheila
Chatenoud, Lucienne
Assuntos: Animals ; Antigens ; Autoantibodies ; Autoantibodies - immunology ; Autoimmune diseases ; Autoimmunity ; Autoimmunity - immunology ; B cells ; B7-H1 Antigen - immunology ; beta-N-Acetylhexosaminidases - immunology ; Biology ; Cell Differentiation - immunology ; Cytokines ; Diabetes ; Diabetes mellitus ; Diabetes Mellitus, Experimental - immunology ; Diabetes Mellitus, Experimental - parasitology ; Diabetes Mellitus, Type 1 - immunology ; Diabetes Mellitus, Type 1 - parasitology ; Disease ; Environmental law ; Fasciola hepatica ; Fasciola hepatica - immunology ; Female ; Gene expression ; Genetic markers ; Health aspects ; Helminths - immunology ; Immunoglobulin G ; Immunomodulation ; Infections ; Inflammatory diseases ; Insulin ; Insulitis ; Interferon ; Interferon-gamma - immunology ; Lectins - immunology ; Lymph nodes ; Lymph Nodes - immunology ; Lymph Nodes - parasitology ; Lymphocytes ; Lymphocytes T ; Macrophages ; Macrophages, Peritoneal - immunology ; Macrophages, Peritoneal - parasitology ; Mammals ; Medicine ; Mice ; Mice, Inbred NOD ; Pancreas ; Pancreas - immunology ; Parasites ; PD-L1 protein ; Peritoneum ; Prevention ; Proteins ; Rodents ; Schistosoma mansoni ; Splenocytes ; Studies ; T cells ; T-Lymphocytes, Regulatory - immunology ; T-Lymphocytes, Regulatory - parasitology ; Transforming Growth Factor beta - immunology ; Type 1 diabetes ; γ-Interferon
É parte de: PloS one, 2014-01, Vol.9 (1), p.e86289-e86289
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Competing Interests: The authors have declared that no competing interests exist.
Conceived and designed the experiments: MEL BAO JPD SD. Performed the experiments: MEL BAO ATH SD. Analyzed the data: MEL BAO ATH MWR AS JPD SD. Contributed reagents/materials/analysis tools: MWR JPD SD. Wrote the paper: MEL BAO ATH MWR AS JPD SD.
Descrição: Infections with helminth parasites prevent/attenuate auto-inflammatory disease. Here we show that molecules secreted by a helminth parasite could prevent Type 1 Diabetes (T1D) in nonobese diabetic (NOD) mice. When delivered at 4 weeks of age (coincident with the initiation of autoimmunity), the excretory/secretory products of Fasciola hepatica (FhES) prevented the onset of T1D, with 84% of mice remaining normoglycaemic and insulitis-free at 30 weeks of age. Disease protection was associated with suppression of IFN-γ secretion from autoreactive T cells and a switch to the production of a regulatory isotype (from IgG2a to IgG1) of autoantibody. Following FhES injection, peritoneal macrophages converted to a regulatory M2 phenotype, characterised by increased expression levels of Ym1, Arg-1, TGFβ and PD-L1. Expression of these M2 genetic markers increased in the pancreatic lymph nodes and the pancreas of FhES-treated mice. In vitro, FhES-stimulated M2 macrophages induced the differentiation of Tregs from splenocytes isolated from naïve NOD mice. Collectively, our data shows that FhES contains immune-modulatory molecules that mediate protection from autoimmune diabetes via the induction and maintenance of a regulatory immune environment.
Editor: United States: Public Library of Science
Idioma: Inglês

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Secreted proteins from the helminth Fasciola hepatica inhibit the initiation of autoreactive T cell responses and prevent diabetes in the NOD mouse

Lund, Maria E ; O'Brien, Bronwyn A ; Hutchinson, Andrew T ; Robinson, Mark W ; Simpson, Ann M ; Dalton, John P ; Donnelly, Sheila Chatenoud, Lucienne

United States: Public Library of Science

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