Chronic low-grade inflammation associated with obesity contributes to insulin resistance and type 2 diabetes. Helminth parasites are the strongest natural inducers of type 2 immune responses, and short-lived infection with rodent nematodes was reported to improve glucose tolerance in obese mice. Here, we investigated the effects of chronic infection (12 weeks) with Schistosoma mansoni, a helminth that infects millions of humans worldwide, on whole-body metabolic homeostasis and white adipose tissue (WAT) immune cell composition in high-fat diet-induced obese C57BL/6 male mice. Our data indicate that chronic helminth infection reduced body weight gain (262%), fat mass gain (289%), and adipocyte size; lowered whole-body insulin resistance (223%) and glucose intolerance (216%); and improved peripheral glucose uptake (+25%) and WAT insulin sensitivity. Analysis of immune cell composition by flow cytometry and quantitative PCR (qPCR) revealed that S. mansoni promoted strong increases in WAT eosinophils and alternatively activated (M2) macrophages. Importantly, injections with S. mansoni-soluble egg antigens (SEA) recapitulated the beneficial effect of parasite infection on whole-body metabolic homeostasis and induced type 2 immune responses in WAT and liver. Taken together, we provide novel data suggesting that chronic helminth infection and helminthderived molecules protect against metabolic disorders by promoting a T helper 2 (Th2) response, eosinophilia, and WAT M2 polarization.-Hussaarts, L., García-Tardón, N., van

Background:The glutamate transporter GLT-1 is regulated by PKC, which promotes its ubiquitination and subsequent endocytosis. Results: Phosphorylation of GLT-1 occurs at Ser-520, whereas ubiquitination is mediated by the ubiquitin ligase Nedd4-2. Conclusion: PKC-promoted endocytosis of GLT-1 requires Nedd4-2-dependent ubiquitination but not its phosphorylation. Significance: Intracellular trafficking of glutamate transporters seems to play a major role in the pathophysiology of the nervous system.