Regulation of Type 2 Diabetes by Helminth-Induced Th2 Immune Responses

Helminth-induced Th2 cytokines increase the number of regulatory T cells and M2 macrophages, resulting in the modulation of the host immune system. Studying parasite-induced immune regulatory mechanisms might contribute to the development of novel therapies for the treatment of inflammatory diseases, including Type 2 diabetes mellitus (T2DM). Previous studies have suggested the progression of obesity-associated metabolic abnormalities is under the pathophysiological control of CD4⁺ T cells. Furthermore, glucose absorption through intestinal epithelium is decreased following infection in a STAT-6-dependent manner. In this study, we investigated whether infection with the gastrointestinal nematode parasite, Heligmosomoides polygyrus, could modulate disease severity in a mouse model of T2DM (KK-Ay/Tajcl). KK-Ay mice were inoculated with infective, third-stage H. polygyrus larvae. Studies were conducted 8 days after infection. Uninfected KK-Ay mice had more elevated serum glucose levels 120 mins after i.p. administration of glucose than mice in the infected group. HOMA-IR, fat accumulation and hepatic FAS gene expression were significantly decreased by H. polygyrus infection. Gene expression of GLUT2 was significantly decreased in infected mice compared with that in uninfected diabetic mice, which is possibly involved in decreased intestinal glucose absorption by parasite infection. In conclusion, helminth-induced Th2 cytokines may reduce T2DM disease severity.