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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies / immunology
  • Autoimmunity / immunology*
  • B7-H1 Antigen / immunology
  • Cell Differentiation / immunology
  • Diabetes Mellitus, Experimental / immunology
  • Diabetes Mellitus, Experimental / parasitology
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / parasitology
  • Fasciola hepatica / immunology*
  • Female
  • Helminths / immunology*
  • Interferon-gamma / immunology
  • Lectins / immunology
  • Lymph Nodes / immunology
  • Lymph Nodes / parasitology
  • Macrophages, Peritoneal / immunology
  • Macrophages, Peritoneal / parasitology
  • Mice
  • Mice, Inbred NOD
  • Pancreas / immunology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / parasitology*
  • Transforming Growth Factor beta / immunology
  • beta-N-Acetylhexosaminidases / immunology

Substances

  • Autoantibodies
  • B7-H1 Antigen
  • Cd274 protein, mouse
  • Lectins
  • Transforming Growth Factor beta
  • Interferon-gamma
  • Chil3 protein, mouse
  • beta-N-Acetylhexosaminidases