Regulation of type 2 diabetes by helminth-induced Th2 immune response

Abstract

Helminth-induced type 2 cytokines increase the number of regulatory T cells and alternatively activated macrophages, resulting in modulation of the host–immune system. Studies on these parasite-induced immunoregulatory mechanisms might contribute to the development of new therapies for inflammatory diseases, including type 2 diabetes (T2D). Previous studies have suggested that progression of obesity-associated metabolic abnormalities is under pathophysiological control of CD4+ T cells. Glucose absorption through the intestinal epithelium reduced after infection in a STAT-6-dependent manner. In this study, we investigated whether infection with the gastrointestinal nematode parasite Heligmosomoides polygyrus (Hp) can modulate T2D-associated pathology in a mouse model (KK-Ay/TaJcl). KK-Ay/TaJcl mice were inoculated with infective third-stage Hp larvae and studied at Day 8 following infection. Uninfected KK-Ay/TaJcl mice showed high blood glucose levels even 120 min after administration of glucose by IP injection. However, it was significantly improved in the infected group. HOMA-IR, fat accumulation and FAS gene expression in the liver were significantly decreased by Hp infection. GLUT2 gene expression in this group was significantly lower than that in the uninfected diabetic mice, which might be related to the decrease in glucose absorption in the parasite-infected intestine. In conclusion, helminth-induced type 2 immune responses might contribute to T2D disease control.

Association of urogenital and intestinal parasitic infections with type 2 diabetes individuals: a comparative study

“…However, the exact mechanisms are not fully understood, this was explained by the anti-inflammatory effect of helminths since helminthiasis lower the circulatory pro-inflammatory cytokines and increase the anti-inflammatory cytokines [ 30 , 31 ]. Helminths also lead to depletion of body energy sources resulting in weight loss and improved metabolic outcomes [ 27 – 29 ] as well as manipulate the gut microbiome that plays an essential role in blood glucose homeostasis [ 30 , 32 ]. The current study findings showed that the proportion of parasitosis was much higher in diabetic individuals and the odds of testing positive for either urogenital schistosomiasis or intestinal parasitic diseases were more than two times higher in T2DM compared to control individuals.…”

“…The mechanisms of both suggest they influence each other. Previous studies showed that some helminths infection or its derived antigens reduce blood glucose and improve insulin sensitivity [27][28][29][30][31]. However, the exact mechanisms are not fully understood, this was explained by the anti-inflammatory effect of helminths since helminthiasis lower the circulatory proinflammatory cytokines and increase the antiinflammatory cytokines [30,31].…”

Gross Ways to Live Long: Parasitic Worms as an Anti-Inflammaging Therapy?

“…Several epidemiological studies have reported an inverse relationship between the incidence of helminth infection and type 2 diabetes (Aravindhan et al, 2010;Chen et al, 2013;Hays et al, 2015), and also serum levels of the pro-inflammatory cytokines IL-6 and GM-CSF (Aravindhan et al, 2010); these studies controlled for age and BMI (and/or income). And again, experimental helminth infections protected mice from type 2 diabetes-associated states such as hyperglycemia and insulin resistance (Wu et al, 2011;Morimoto et al, 2016;Pace et al, 2018), while anthelmintic treatment elevated blood glucagon and insulin resistance, and several circulating pro-inflammatory cytokines (Tahapary et al, 2017;Rajamanickam et al, 2019Rajamanickam et al, , 2020. Regarding atherosclerosis, the burden of Opisthorchis felineus (cat liver fluke) in cadavers was found to be negatively correlated with the severity of aortic atherosclerosis (Magen et al, 2013).…”

The Gastrointestinal Helminth Heligmosomoides bakeri Suppresses Inflammation in a Model of Contact Hypersensitivity

“…Various epidemiological studies have drawn a link between the incidence of helminth infection and reduction in allergic and inflammatory diseases (1)(2)(3)(4). In seeking mechanisms by which this might occur, experimental models have linked helminth-induced regulatory T and B cells (Tregs and Bregs, respectively), to the dampening of responses to allergens (5,6) such as HDM (7,8), ovalbumin (OVA) (9,10) and peanut (11), and to the amelioration of inflammation in a number of disease models including colitis (12)(13)(14), experimental autoimmune encephalitis (15), and diabetes (16,17).…”