Macrophage activation and immunometabolism

Macrophage activation and immunometabolism refers to the intrinsic link between a macrophage's metabolic state and its functional phenotype (O'Neill et al., 2016). Upon activation, macrophages undergo metabolic reprogramming to meet the energetic and biosynthetic demands of their specific immune roles (Kelly & O'Neill, 2015). Pro-inflammatory (M1-like) macrophages generally shift toward aerobic glycolysis and a truncated tricarboxylic acid (TCA) cycle, leading to the accumulation of metabolites like succinate and itaconate that further signal inflammatory responses (Mills et al., 2016). Conversely, anti-inflammatory (M2-like) macrophages rely more heavily on oxidative phosphorylation and fatty acid oxidation to support tissue repair and resolution of inflammation (Geeraerts et al., 2017). Dysregulation of these metabolic programs is a hallmark of many diseases, including cancer, where the tumor microenvironment can polarize macrophages to an immunosuppressive state, and atherosclerosis, where metabolic stress drives chronic inflammation (Viola et al., 2019). While not a single molecular target, the pathways governing macrophage immunometabolism are being explored for therapeutic intervention to re-polarize immune cells in various disease contexts.

Other names

Macrophage polarizationMetabolic reprogramming of macrophagesMyeloid immunometabolism

Modulation of intracellular metabolic pathways, such as glycolysis and the tricarboxylic acid cycle, to shift macrophage functional phenotypes between pro-inflammatory and anti-inflammatory states.