Prevention of Type 1 diabetes in NOD mice by helminth infection (131.36)

Abstract

Abstract Parasitic helminth infection has been shown to modulate pathologic inflammation associated with allergy and autoimmune disease. The aim of this study was to examine whether infection with a helminth parasite could down-regulate the onset of type 1 diabetes in NOD mice and to examine the mechanisms involved in this protection. At 5 weeks of age, NOD mice were infected with Heligmosomoides polygyrus(Hp). At 36 weeks of age, these mice were compared with uninfected mice for the onset of type 1 diabetes (T1D). 70% of uninfected NOD mice became diabetic but only 10% of Hp infected mice developed T1D. Moreover, Hp infection also significantly reduced the development of the more aggressive cyclophosphamide-induced T1D in NOD mice with 5% developed in Hp-infected group compared to 78% in uninfected group. Further studies showed that infection with Hp in NOD mice: markedly inhibited insulitis in the pancreas;elevated IL-4 and IL-13 levels in mesenteric and pancreatic lymph nodes as well as in spleens;increased the frequency of CD4+ CD25+ Foxp3+ Tregs in mesenteric and pancreatic lymph nodes;led to a consistent, massive accumulation of mononuclear cells in the regions of pancreatic fat. These findings suggest that infection with Hp significantly inhibits the onset of T1D in NOD mice by influencing lymphocyte trafficking to the β-islet cells in the context of increased Th2 and T regulatory cell populations.