Abstract
There is a known inverse correlation between chronic helminth infections and metabolic diseases. Despite strong evidence that prior helminth infection exerts a protective effect against the development of metabolic disease, a major gap exists in understanding the mechanism(s) underlying this protection. We recently published that S. mansoni infection induces dramatic transcriptional alterations in hepatic macrophage metabolism, and that this correlates with protection from high fat diet (HFD) induced atherosclerosis and glucose intolerance in male ApoE−/− mice. Since it has previously been shown that during S. mansoni infection the majority of macrophages are monocyte derived, and that schistosome antigens circulate systemically, we sought in the present study to determine the broad effects of S. mansoni exposure on the myeloid lineage using the ApoE−/− HFD model. Surprisingly, we discovered that macrophages derived from the bone marrow of S. mansoni infected male mice have dramatically increased oxygen consumption and mitochondrial mass. This shift is accompanied by increased glucose shuttling into TCA cycle intermediates and decreased cholesterol esters. When we examined the role of biological sex in schistosome induced modulation. We found that S. mansoni infection does not reliably protect ApoE−/− female mice from HFD induced weight gain or glucose intolerance. The sex-dependent effect of infection extends to myeloid precursors, where bone marrow derived macrophages from infected females display the opposite metabolic phenotype as those from infected males. Overall, these data present the first evidence that S. mansoni systemically modulates the myeloid compartment in a sex-dependent manner.
