Short-term helminth infection inhibits type 1 diabetes independently of the Th2-type response (119.5)

Abstract

Abstract Helminth infection can control a number of autoimmune inflammatory diseases in experimental models including type 1 diabetes (T1D).The molecular mechanisms of heminth mediated control of T1D are not yet determined,but it is generally thought that the associated immunoregulation is caused by the potent and highly polarized Th2-type response driven by IL-4.In these studies, nonobese diabetic (NOD) IL-4-/- mice were infected with a strictly enteric nematode parasite.Remarkably,we showed that the helminth-induced control of T1D remained intact. Elevations in CD4+ T cell STAT6 phosphorylation were inhibited,while suppression of STAT1 phosphorylation was sustained,as were increases in FOXP3-,CD4+T cell IL-10 production.Furthermore, protection still occurred if parasites were expulsed with an anti-helminth Rx after only two weeks infection.Oral antibiotic treatment did not effect helminth-mediated protection indicating that intestinal microbiota did not play a major role.Blockade of IL-10 signaling in NOD-IL-4-/-,but not NOD mice,during this short interval abrogated protective effects resulting in pancreatic β-cell destruction and T1D development.These studies indicate that helminth infection triggers multiple immune regulatory components that are induced and can act independently.Their combined effects help explain the potency of helminth-mediated control of pathologic inflammation and suggest future strategies for helminth-mediated therapeutic treatment of this autoimmune disease.