Macrophage Activation and Polarization

Macrophages populate virtually all tissues in the body and have a myriad of functions in host defense and homeostasis. Macrophages are exquisitely tuned to their microenvironment and alter their phenotype and function in response to both cell–cell interactions and soluble signals such as cytokines. This changeability is often called ‘polarization’ or ‘activation.’ On one end of the spectrum, when a macrophage is stimulated with bacterial products and the cytokine interferon-gamma, it increases its antibacterial killing capacity and is often called ‘M1’ or ‘classically activated.’ On the other end of the spectrum are macrophages much reduced in antimicrobial capacity which promote fibrogenic or wound healing responses and are often called ‘M2’ or ‘alternatively activated.’ Generally measures of changes in surface markers, transcripts, or functions are performed to characterize polarization. Although this dichotomy has been enthusiastically accepted by the research community, it is not an accurate measure of the full range of macrophage phenotypes, is challenging to apply to macrophages isolated from tissues, and has been challenging to translate to human studies. Herein we discuss the macrophage heterogeneity and polarization in mice and humans.