Macrophage Polarization in Inflammatory Diseases

Liu, Yan-Cun; Zou, Xian-Biao; Chai, Yan-Fen; Yao, Yong-Ming

Both M1 and M2 phenotype macrophages are involved in parasite infestation, depending on the subtype and duration of parasite infestation models. In general, macrophages undergo a dynamic switch toward M2 phenotype. For instance, during the early stage of Taenia crassiceps infestation, it is characterized by responses of Th1-driven M1 phenotype macrophages, however, as infection goes to a late stage, Th2-driven IL-4-mediated M2 phenotype would become dominant with a decreased parasite burden [22] . In addition, different subtypes of parasite show different macrophage phenotypes during infection. Toxoplasma gondii has been shown to have three distinct clonal lineages, type I, type II, and type III, and they differ in virulence. Type I and III infected macrophages are alternatively activated through activation of STAT6 by Toxoplasma rhoptry kinase ROP16, but type II infected macrophages are classically activated through activation of NF-κB by Toxoplasma dense granule protein GRA15 [35] . Moreover, it is not a terminal differentiation for M2 phenotype in parasite infestation. In a recent study, utilizing a murine model of filarial infection demonstrated that macrophages which are exposed to Th2 cytokines and anti-inflammatory signals in vivo for a long time could still develop a classically activated phenotype in response to LPS or IFN-γ, and become antimicrobial through producing NO [36] .