Macrophage Polarization in Inflammatory Diseases

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

M2 phenotype macrophages are believed to play pivotal roles in regulating various pathologic features of helminth infestation, including suppression of T cell response, regulation of fibrosis, and formation of multinucleated giant cells in parasite-induced granulomas. Some important molecules are involved in this process. For example, in Leishmania infantum infection, Dectin-1 and mannose receptor, two kinds of C-type lectin receptors (CLRs) expressed on macrophages, respectively activate Sykp47phox and arachidonic acid-NADPH oxidase signaling pathways, and they are crucial for reactive oxygen species (ROS) production and also trigger Syk-coupled signaling for caspase-1 induced IL-1β release. In contrast, specific intercellular adhesion molecule-3-grabbing nonintegrin receptor 3 (SIGNR3), another kind of CLRs, helps parasite resilience through inhibition of the leukotriene (LTB) 4-IL-1β axis. Therefore, CLRs are key modulators for macrophage polarization, and are served as potential targets for prevention as well as treatment of Leishmania infantum infection [37] . Arg1 is not only an important marker of M2 phenotype macrophages but also a regulator of the immune response in parasite infestation. A study using myeloid cell restricted Arg1 deficiency Schistosoma mansoni infection model suggested that Arg1 appeared to be a key mediator for the development of helminth infestation through restraining both unrestricted Th2-mediated fibrotic pathology and intestinal damage associated with increased Th1/Th17 cytokines, nitric oxide synthase (NOS) 2 levels, and endotoxemia [38, 39] . However, it is not a generalized effect in the pathogenesis of parasite infestation. Arg1 blockade or deficiency in hematopoietic and endothelial cell lineages had little effect on response to acute orchronic infection by Trichuris muris [40] .