Schistosome and intestinal helminth modulation of macrophage immunometabolism

Abstract

SummaryMacrophages 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.

Polarization of intestinal tumour-associated macrophages regulates the development of schistosomal colorectal cancer

“…In this study, we found that the number of TAMs and the proportion of M2 TAMs in schistosomal CRC tissues were much higher than that in non-schistosomal CRC tissues; both differences were significant. Cortes-Selva D found that schistosomiasis can induce a strong Th2-biased immune response in the host and polarize macrophages into a broad M2 phenotype, consistent with the results reported here 43 . The number of TAMs continues to rise during tumour development, and the proportion of M2 macrophages increases significantly.…”

Immunometabolism: Towards a Better Understanding the Mechanism of Parasitic Infection and Immunity

“…These studies not only suggest that glucose and lipid metabolic remodeling underpins the capacity of macrophage function, but also indicate that targeting PTEN may prevent the fibrosis induced by Schistosoma sp. Besides, other underlying metabolic events related with the infection of the parasite have been reviewed by Diana and Keke [As reviewed in Reference ( 38 )].…”

Sweet talk: Metabolic conversations between host and microbe during infection

“…They provide an overview of metabolic mechanisms for regulating immune activity and defence against infection, including the influence of cellular metabolism on epigenetic regulation, 7 post‐translational protein modification, 8 immune cell trafficking 9 and intestinal homeostasis 10 . This second part of the series provides specific examples of immunometabolism in action during particular infections, highlighting metabolic regulation in macrophages during helminth infection, 11 in T cells during chronic viral infections (CVIs) 12 and at the interface between innate and adaptive immunity to Mycobacterium tuberculosis infection 13 …”

“…In the first article in this issue, Cortes‐Selva and Fairfax discuss the elegance of macrophage metabolic regulation during helminth infection, with a particular emphasis on their expertise in Schistosoma mansoni infection 11 . Readers who enjoyed the review from Gerós et al in the first part of this series will appreciate Cortes‐Selva and Fairfax’s discussion of the central role of macrophages in iron regulation.…”