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

• Published in: PloS one Vol. 9; no. 1; p. e86289
• Main Authors: Lund, Maria E, O'Brien, Bronwyn A, Hutchinson, Andrew T, Robinson, Mark W, Simpson, Ann M, Dalton, John P, Donnelly, Sheila
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21.01.2014; Public Library of Science (PLoS)
• Subjects: 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
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0086289

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.