Immunometabolism: From basic mechanisms to translation

Abstract

Immunometabolism has emerged as a major mechanism central to adaptive and innate immune regulation. From early observations that inflammatory cytokines were induced in obese adipose tissue and that these cytokines contributed to metabolic disease, it was clear that metabolism and the immunological state are inextricably linked. With a second research wave arising from studies in cancer metabolism to also study the intrinsic metabolic pathways of immune cells themselves and how those pathways influence cell fate and function, immunometabolism is a rapidly maturing area of research. Several key themes and goals drive the field. There is abundant evidence that metabolic pathways are closely tied to cell signaling and differentiation which leads different subsets of immune cells to adopt unique metabolic programs specific to their state and environment. In this way, metabolic signaling drives cell fate. It is also apparent that microenvironment greatly influences cell metabolism.Immune cells adopt programs specific for the tissues where they infiltrate and reside.Ultimately, a central goal of the field is to apply immunometabolism findings to the discovery of novel therapeutic strategies in a wide range of diseases, including cancer, autoimmunity, and metabolic syndrome. This review summarizes these facets of immunometabolism and highlights opportunities for clinical translation. K E Y W O R D S autoimmunity, immune-mediated diseases, infectious diseases, metThis article introduces a series of reviews covering Immunometabolism: From Basic Mechanisms to Translation appearing in Volume 295 of Immunological Reviews.

Mitochondrial phenotypes in purified human immune cell subtypes and cell mixtures

“…There has been emerging interest in determining what dictates the natural variability of immune cell subtype distributions, which are in large part driven by intrinsic genetic, environmental, and behavioral factors in humans 13 . In relation to the metabolic properties of specific immune cells subtypes, most data is derived from rodents or from human leukocytes often activated in vitro , which clearly demonstrates that immune cells exhibit specific metabolic requirements depending on their state 3, 54, 55 . Our analysis first confirmed the influence of sex and age on the proportions of circulating innate and adaptive cells, likely reflecting the effect of genetic and environmental factors throughout life.…”

The Effects of Type 2 Diabetes Mellitus on Organ Metabolism and the Immune System

“…Studies on immunometabolism have indicated that the metabolic states and immunological processes are inherently interconnected ( 6 ). In this scenario, metabolites derived from the host or microbiota regulate immunological responses during health and disease ( 6 ).…”

“…Studies on immunometabolism have indicated that the metabolic states and immunological processes are inherently interconnected ( 6 ). In this scenario, metabolites derived from the host or microbiota regulate immunological responses during health and disease ( 6 ). Accordingly, in obese individuals, expanded adipose tissue at different locations, by initiating and perpetuating the inflammation, induces a chronic low-level inflammatory state that promotes IR ( 4 ).…”

Enhanced lipid biosynthesis in human tumor-induced macrophages contributes to their protumoral characteristics

“…In the last decade, the field of immunometabolism has provided data on the metabolic profile of immune cells and on the mechanisms through which cellular metabolism shapes the immune cells' activation state and function. 15 For example, in vitro classically activated M1 macrophages, use anaerobic glycolysis, protein and fatty acid (FA) synthesis metabolic pathways, 16 whereas alternatively activated M2 macrophages are mainly using oxidative phosphorylation (OXPHOS) for energy metabolism. 17 However, little is known about the programming and the specific metabolic phenotype of human macrophages in the context of cancer.…”