Functional aspects, phenotypic heterogeneity, and tissue immune response of macrophages in infectious diseases

de Sousa, Jorge Rodrigues; Da Costa Vasconcelos, Pedro Fernando; Quaresma, Juarez Antonio Simões

Among the phenotypes of M2 macrophages, M2a, M2b, and M2c macrophages are characterized by the presence of arginase (Arg). [47] [48] [49] These subpopulations express a cell-surface scavenger receptor that recognizes haptoglobin-hemoglobin complexes used to identify M2 macrophages and is labeled with CD163. Moreover, a previously unrecognized subpopulation of M2 macrophages, M2d, has been described, but the molecules responsible for the differentiation of M0 macrophages into M2d macrophages remain unknown. However, this population participates in the angiogenesis response, producing interleukin (IL)-10 and vascular endothelial growth factor (Table 1) . [50] [51] [52] Macrophages are capable of differentiating into six additional subpopulations: regulatory (Mreg), hematophage-associated (Mha), oxidative (Mox), M3, M4, and M17 macrophages (Table 1) . [53] [54] [55] [56] Mreg macrophages respond to the stimulation of Treg cells and are responsible for inducing the repair response and inhibiting triggering of mechanisms that produce pro-inflammatory cytokines in tissue lesions. [57] [58] [59] Mox macrophages differ from the other cell types in expressing oxidized 1palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine and producing HO-1 and sulfiredoxin-1. [60] [61] [62] Mox macrophages are also associated with triggering of oxidative responses (Table 1) . [60] [61] [62] Table 1 Macrophage phenotypes, stimulating factors, genes, primary markers, and functions described in the scientific literature Pro-inflammatory