Complexity of macrophage metabolism in infection

Macrophages are the prominent innate immune cells to combat infection and then restore tissue homeostasis after clearance of pathogens. Intracellular metabolic reprogramming is required for macrophage activation and function, as such adaptations confer macrophages with sufficient energy and metabolites to support biosynthesis and diverse functions. During the last 10 years, knowledge in this field has been greatly extended by outstanding advances demonstrating that several metabolic intermediates possess the ability to directly control macrophage activation and effector functions by various mechanisms. Of note, citrate and succinate contribute to the inflammatory activation of macrophages while tricarboxylic acid cycle-derived metabolite itaconate has a variety of immunomodulatory effects. Such progress not only encourages a further exploration into the emerging new area immunometabolism, but also provides potential therapeutic targets to control unwanted inflammation due to infection.