Schistosome and intestinal helminth modulation of macrophage immunometabolism

Macrophages are fundamental to sustain physiological equilibrium and to regulate the pathogenesis of parasitic and metabolic processes. The functional heterogeneity and immune responses of macrophages are shaped by cellular metabolism in response to the host's intrinsic factors, environmental cues and other stimuli during disease. Parasite infections induce a complex cascade of cytokines and metabolites that profoundly remodel the metabolic status of macrophages. In particular, helminths polarize macrophages to an M2 state and induce a metabolic shift towards reliance on oxidative phosphorylation, lipid oxidation and amino acid metabolism. Accumulating data indicate that helminth-induced activation and metabolic reprogramming of macrophages underlie improvement in overall whole-body metabolism, denoted by improved insulin sensitivity, body mass in response to high-fat diet and atherogenic index in mammals. This review aims to highlight the metabolic changes that occur in human and murine-derived macrophages in response to helminth infections and helminth products, with particular interest in schistosomiasis and soil-transmitted helminths.