Sex-specific Schistosomiasis induced metabolic modulation of the myeloid lineage

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 previously found that Schistosoma 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. We sought in the present study to determine the broad effects of S. mansoni exposure on the myeloid lineage using the ApoE-/- HFD model. We uncovered that macrophages derived from the bone marrow of S. mansoni infected male mice have dramatically increased oxygen consumption and mitochondrial mass compared to those from uninfected mice. 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 the metabolic phenotype of bone marrow derived macrophages from infected females are the opposite of those from infected males. Overall, these data present the first evidence that S. mansoni systemically modulates the myeloid compartment in a sex-dependent manner. Overall design: mRNAseq of BMDM from 4 uninfected male ApoE-/- mice on HFD, 5 schistosoma mansoni infected male ApoE-/- mice on HFD, 4 uninfected female ApoE-/- mice on HFD, 5 Schistosoma mansoni infected. All samples are from 10 week post infection/mock infection ApoE-/- mice on HFD