Perspective Chapter: Macrophages Plasticity and Immune Metabolism

Macrophages are phagocytic cells that reside within body tissues. They can either be derived from circulating monocytes or can arise during the embryonic stage of fetal development. Tissue macrophages are predominantly of embryonic origin. But can result from differentiation of circulating monocytes to become resident macrophages either in pathological or physiological state. Macrophages are classified based on their tissue location and method of activation. Classically activated macrophages are the M1 phenotype while alternatively activated macrophages are M2 phenotype. M1 macrophages are pro-inflammatory since they secrete cytokines that attract inflammatory mediators. They are majorly activated by either interferon-gamma or lipopolysaccharide molecules. M2 macrophages are anti-inflammatory and mediate tissue healing and repair. They are activated by cytokines such as interleukin four, ten, and thirteen. The metabolic profiles of these classes of macrophages are intrinsically different and complex yet intertwined. M1 macrophages depend on aerobic glycolysis for energy production while M2 macrophages rely on aerobic fatty acid oxidation pathways. These metabolic pathways optimize macrophage functioning. Regulation of both activation and metabolism depends on transcriptional factors such as STAT 1 and 6, and IRF. Defects in these pathways lead to development of disorders related to macrophage activation and metabolism.