Credit: NPG

Helminths—parasitic worms that infect millions of individuals worldwide—might have beneficial metabolic effects by inducing type 2 immune responses and reducing chronic low-grade inflammation in obesity. In a new study, diet-induced obese mice infected with a blood-borne helminth, Schistosoma mansoni, had improved insulin sensitivity and increased numbers of M2 macrophages in white adipose tissue (WAT).

The investigators fed mice with either a high-fat diet (HFD) or a low-fat diet (LFD) for 6 weeks, before infecting both groups with S. mansoni or a sham infection and monitoring the mice for a further 12 weeks. HFD-fed mice gained less weight when infected with S. mansoni compared with the sham control mice, which was attributed to lower body-fat mass but not a change in lean body mass. Food intake and energy expenditure were unaffected. S. mansoni infection also improved insulin sensitivity and glucose uptake in the HFD-fed mice, which was impaired in control mice receiving a sham infection. Interestingly, S. mansoni infection did not affect body weight, fat mass or any metabolic parameters in LFD-fed mice, which suggests that the metabolic improvement observed in HFD-fed mice is independent of any helminth-induced pathology.

As the balance between M1 and M2 macrophages can influence insulin sensitivity in adipocytes, the investigators determined if S. mansoni-associated type 2 immune responses might influence the macrophage composition of WAT. S. mansoni infection increased the ratio of M2 to M1 macrophages in WAT from both LFD and HFD-fed mice.

Finally, to determine if these effects were specific to S. mansoni or simply the result of parasitic infection, the investigators used soluble antigens derived from S. mansoni eggs. Notably, macrophage changes observed in WAT with whole parasite infection were recapitulated with only the antigens, with an increased number of M2 compared with M1 macrophages, an increase in gene expression of type 2 cytokines and improved insulin sensitivity in obese mice. The investigators believe that helminth-derived molecules might be useful therapeutic agents that target the immune system to treat metabolic disorders.