Schistosoma mansoni infection metabolically reprograms the myeloid lineage in a mouse model of metabolic disease

We studied the effects of helminth infection and cytokine activation in the metabolic signatures of bone marrow derived macrophages using an approach that integrated transcriptomics, metabolomics, and lipidomics in a metabolic disease prone mouse model. We demonstrate that bone marrow derived macrophages (BMDM) from S. mansoni infected male ApoE-/- mice have dramatically increased mitochondrial respiration compared to those from uninfected mice. This change is associated with increased glucose and palmitate shuttling into TCA cycle intermediates, increased accumulation of free fatty acids, and decreased accumulation of cellular cholesterol esters, tri and diglycerides. Systemic injection of IL-4 complexes is unable to recapitulate either reductions in systemic glucose AUC or the re-programing of BMDM mitochondrial respiration seen in infected males. Finally, the metabolic reprogramming of male myeloid cells is transferrable via bone marrow transplantation to an uninfected host, indicating maintenance of reprogramming in the absence of sustained antigen exposure. Conclusions: Our findings identify a transferable and long-lasting reprograming of the metabolic signature of macrophages by helminth infection that is sufficient to improve systemic glucose metabolism thus providing a mechanistic insight into the factors regulating the beneficial roles of infection in metabolic disease RNA-seq of bone marrow derived macrophages from uninfected, S. mansoni infected or IL-4c treated male mice.