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J Immunol. 2009 Aug 1;183(3):1577-86. doi: 10.4049/jimmunol.0803803. Epub 2009 Jul 8.

Infection with a helminth parasite attenuates autoimmunity through TGF-beta-mediated suppression of Th17 and Th1 responses.

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Immune Regulation Research Group, School of Biochemistry and Immunology, Trinity College, Dublin, Ireland.


The lower incidence of allergy and autoimmune diseases in developing countries has been associated with a high prevalence of parasitic infections. Here we provide direct experimental evidence that parasites can exert bystander immunosuppression of pathogenic T cells that mediate autoimmune diseases. Infection of mice with Fasciola hepatica resulted in recruitment of dendritic cells, macrophages, eosinophils, neutrophils, and CD4(+) T cells into the peritoneal cavity. The dendritic cells and macrophages in infected mice expressed IL-10 and latency-associated peptide, and they had low surface expression of costimulatory molecules and/or MHC class II. Furthermore, most CD4(+) T cells in the peritoneal cavity of infected mice secreted IL-10, but not IFN-gamma or IL-4. There was a less significant expansion of CD4(+)Foxp3(+) T cells. F. hepatica-specific Tr1-type clones generated from infected mice suppressed proliferation and IFN-gamma production by Th1 cells. Infection was associated with suppression of parasite-specific Th1 and Th2 responses, which was reversed in IL-10-defective mice. Infection with F. hepatica also exerted bystander suppression of immune responses to autoantigens and attenuated the clinical signs of experimental autoimmune encephalomyelitis. Protection was associated with suppression of autoantigen-specific IFN-gamma and IL-17 production. The suppression of Th1 and Th17 responses and attenuation of experimental autoimmune encephalomyelitis by F. hepatica was maintained in IL-10(-/-) mice but was reversed by neutralization of TGF-beta in vivo. Our study provides evidence that F. hepatica-induced IL-10 subverts parasite-specific Th1 and Th2 responses, but that F. hepatica-induced TGF-beta plays a critical role in bystander suppression of autoantigen-specific Th1 and Th17 responses that mediate autoimmune diseases.

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