Polarization and functional plasticity of macrophages in regulating innate immune response

Abstract

Innate immune system is the first line of resistance that protects the host body from invasion of pathogens. During this innate immune response process, macrophages are well known to be the powerful leading players located throughout the body in defecting attacks. Originated from bone marrow, monocyte-macrophage lineage still manifests hallmarks of plasticity and diversity. Toll-like receptor (TLR) or interferon gamma (IFNγ) drives macrophages into M1 (classical) activation while IL-4/IL-13 or IL-10 induces M2 (alternative) activation. Different phenotypes of macrophages have distinct biological functions, transcriptional profiles, signaling pathways and cytokines along with chemokine framework. Classical M1 macrophages show strong pro-inflammatory and antimicrobial abilities while M2 macrophages are skilled at anti-inflammation, wound healing and fibrosis. Researches have shown that under different pathological conditions, macrophages are programmed to be different phenotypic subsets and play disparate immunomodulation. However, under the intricate microenvironment, there might be mixed populations instead of a kind of unique phenotypic macrophages. Evidences also show that macrophages can be converted from one phenotype to another according to microenvironmental signals (cytokines, chemokines, growth factors, and microbial-associated molecule patterns). A better understanding of the mechanisms of plasticity and polarization of macrophages will shine new lights into the mechanisms underlying the innate inflammation diseases and suggest promising therapeutic targets.