A guide to immunometabolism for immunologists

Key Points Immunometabolism describes the changes that occur in intracellular metabolic pathways in immune cells during activation. Six major pathways have been studied in immune cells in detail: glycolysis, the tricarboxylic acid (TCA) cycle, the pentose phosphate pathway, fatty acid oxidation, fatty acid synthesis and amino acid metabolism. Glycolysis and fatty acid synthesis are key features of lipopolysaccharide (LPS)-activated macrophages; by contrast, interleukin-4 (IL-4)-activated macrophages mainly use oxidative phosphorylation and fatty acid oxidation to generate energy. Effector T cells are highly glycolytic whereas memory T cells have an oxidative metabolism. Metabolites, such as succinate and citrate, and enzymes, such as pyruvate kinase isoenzyme M2 (PKM2), glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and enolase, have roles outside of metabolism that promote specific events during immune cell activation. Small molecules can target metabolic pathways and alter the phenotype of immune cells, raising the possibility of therapeutic intervention Immunometabolism is emerging an important area of immunological research, but for many immunologists the complexity of the field can be daunting. Here, the authors provide an overview of six key metabolic pathways that occur in immune cells and explain what is known (and what is still to be uncovered) concerning their effects on immune cell function. In recent years a substantial number of findings have been made in the area of immunometabolism, by which we mean the changes in intracellular metabolic pathways in immune cells that alter their function. Here, we provide a brief refresher course on six of the major metabolic pathways involved (specifically, glycolysis, the tricarboxylic acid (TCA) cycle, the pentose phosphate pathway, fatty acid oxidation, fatty acid synthesis and amino acid metabolism), giving specific examples of how precise changes in the metabolites of these pathways shape the immune cell response. What is emerging is a complex interplay between metabolic reprogramming and immunity, which is providing an extra dimension to our understanding of the immune system in health and disease.