Helminth infection modulates number and function of adipose tissue Tregs in high fat diet-induced obesity

Abstract

BackgroundEpidemiological and experimental studies have shown a protective effect of helminth infections in weight gain and against the development of metabolic dysfunctions in the host. However, the mechanisms induced by the parasite that regulate the development of metabolic diseases in the host are unclear. The present study aimed to verify the influence of Heligmosomoides polygyrus infection in early stages of high fat diet-induced obesity. Principal FindingsThe presence of infection was able to prevent exacerbated weight gain in mice fed with high fat diet when compared to non-infected controls. In addition, infected animals displayed improved insulin sensitivity and decreased fat accumulation in the liver. Obesity-associated inflammation was reduced in the presence of infection, demonstrated by higher levels of IL10 and adiponectin, increased infiltration of Th2 and eosinophils in adipose tissue of infected animals. Of note, the parasite infection was associated with increased Treg frequency in adipose tissue which showed higher expression of cell surface markers of function and activation, like LAP and CD134. The infection could also revert the loss of function in Tregs associated with high fat diet. ConclusionThese data suggest that H. polygyrus infection can prevent weight gain and metabolic syndrome in animals fed with high fat diet associated with modulations of adipose tissue Treg cells. Author summaryHelminth infections are known to modulate the immune system being responsible for protecting the host from developing allergic and autoimmune disorders (Hygiene Hypothesis). We hypothesized that the same immunomodulatory effect can have an impact on immunometabolic diseases, such as obesity and its linked diseases such as type 2 diabetes. Weight disorders have reached epidemic levels, nearly tripling since 1975 and being responsible for almost 5 million premature deaths each year. To test our hypothesis C57BL/6 male mice were fed control or high fat diet, for five weeks, in the presence or not of Heligmosomoides polygyrus infection. Weight gain, development of metabolic disorders, inflammation and cellular migration to the adipose tissue were evaluated. In accordance with our hypothesis, we found that the presence of infection prevented the exacerbated weight gain and also improved metabolic parameters in animals fed a high fat diet. This was associated with the infections ability to modulate parameters of a cell responsible for regulatory functions: Tregs. In the light of these findings, helminth infection could be protective against weight gain and metabolic disturbances.