Microglia/macrophage polarization: Fantasy or evidence of functional diversity?

Microglia and non-parenchymal macrophages are increasingly recognized to play critical roles in the central nervous system (CNS) health and disease. Accumulating evidence suggests that these mononuclear phagocytes do not constitute stereotypical cell populations, but rather polarize into a variety of phenotypes at different stages of CNS development, stresses, and diseases. This commentary aims to discuss our current consensus and controversy on microglia/macrophage phenotypes. Collective single-cell level evidence validates the concept of microglia/macrophage polarization, while suggests multi-polarity instead of dichotomic polarization. Characterizing the functions of a specific microglia/macrophage phenotype is challenging yet essential to translate our scientific discoveries into clinical application.