Immunometabolism

Immunometabolism is a research fiel that provides new insights into the dynamic cross-talk between the immune system (immunity) and metabolic process of an organism (metabolism). Immunometabolism tries to understand how metabolism controls the function of immune cells. It can be studied at a macroscopic level (e.g. in adipose tissues (see figure 1) or in a tumor microenvironment) and at a microscopic level, the cellular bioenergetics of immune cells (see Figure 2).

The activation, growth and proliferation, fonction and homeostasis of immune cells are intimately linked to dynamic changes in cellular metabolism configurations. The utilization of particular metabolic pathways is controlled by growth factors and nutrient availability (didacted by competition between other interacting cells) and by the balance of internal metabolitesn reactive oxygen species (ROS) and reducing/oxidizing substrates. Major metabolic pathways (see Figure 2) that shape the immune cell response include glycolysis, the tricarboxylic acid (TCA) cycle, the pentose phosphate pathway (PPP), fatty acid oxydation (FAO), fatty acid synthesis (FAS) and amino acid (AA) metabolism (e.g. glutamine, arginine, tryptophan). The various immune cell subsets use distinct metabolic pathways to promote cell survival, lineage generation and function. For example, inflammatory M1 macrophages or rapidly proliferating effector T cells, including T helper 1 (TH1), TH17 and cytotoxic CD8+ T cells, use metabolic pathways that support cell proliferation and production of cytokines, such as glycolysis or fatty acid synthesis. M2 macrophages or immunosuppressive regulatory T (Treg) cells use metabolic pathways which inhibit inflammatory signals and are associated with suppressive functions, such as TCA cycle and fatty acid oxidation. Linking metabolism and inflammation/immunity is an approach to understand and possibly target low-grade-chronic inflammation and its associated pathologies, such as obesity (T2D), cancer, autoimmune and autoinflammatory diseases.