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PLoS One. 2014 Jan 21;9(1):e86289. doi: 10.1371/journal.pone.0086289. eCollection 2014.

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

Author information

1
School of Medical and Molecular Biosciences, University of Technology Sydney, New South Wales, Australia.
2
School of Biological Sciences, Queen's University Belfast, Belfast, Northern Ireland.
3
Institute of Parasitology, McDonald Campus, McGill University, St. Anne de Bellevue, Quebec, Canada.
4
The i3 Institute, University of Technology Sydney, New South Wales, Australia.

Abstract

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.

PMID:
24466007
PMCID:
PMC3897667
DOI:
10.1371/journal.pone.0086289
[Indexed for MEDLINE]
Free PMC Article

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