The spectrum of macrophage activation by immunometabolism

Abstract

Macrophages are heterogeneous and plastic, and play several diverse functions in immune responses. Emerging data provide evidence of multiple roles for metabolic pathways in the control of macrophage effector functions. The diverse functions of macrophages are categorized into two main subsets: classical activated macrophages (M1) and alternative activated macrophages (M2). M1 macrophages secrete pro-inflammatory cytokines and reactive oxygen species and migrate into inflamed sites as a part of host defenses. On the other hand, M2 macrophages are involved in immune homeostasis by producing anti-inflammatory cytokines and phagocytosing apoptotic cells. Metabolic reprogramming of environmental or cellular nutrients such as glucose, lipids and amino acids supports this diversity. Mechanistically, the mammalian target of rapamycin (mTOR) network plays important roles in the effector functions of macrophages by modulating cellular metabolism and regulating gene expression at the transcriptional and translational levels. In this review, we outline immunometabolism and provide insights into metabolic regulation by mTOR in macrophages.