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

proapoptotic action of TGF-β. 290,291 Viral influenza infections have been linked to lung injury induced by M1 macrophage-associated cytokines, including TNF-α, IFN-γ, and IL-6. Furthermore, these lung lesions might be attenuated in coinfection by Staphylococcus aureus, which is normally present in the airway mucosal microbiota, because of the bacterium's ability to stimulate the expression of M2 macrophages. [292] [293] [294] Conversely, in the pathogenesis of coronavirus and cytomegalovirus infections, the lesions that develop are related to the induction of an inflammatory environment mediated by M2 macrophages, which indicates that viral agents can still benefit from the induction of specific tissue environments related to the Th2 response and, consequently, tissue repair and induction of tissue fibrosis. 287, [295] [296] [297] [298] [299] In mice experimentally infected with Schistosoma japonica, liver fibrosis was associated with the presence of M2 macrophages, which exhibited increased regulation of Notch1/Jagged1 signals, and the blockade of this expression reversed the M2 phenotype and, subsequently, the associated fibrosis. 300 In another study, induction of the M2 phenotype in Schistosoma mansoni infections elicited a low-grade chronic inflammatory response that was associated with insulin resistance in obese patients. 301 Leishmania infection development depends on both the immune response pattern and the Leishmania species. Thus, as described for leprosy, the clinical evolution of leishmaniasis depends on the interaction of the infectious agent and M1 or M2 macrophages, with the M2 subpopulation related to the process of disease progression. 302, 303 Lastly, in rats experimentally infected with Toxoplasma gondii, peritoneal macrophages in the pre-gestational phase were primarily composed of M1 macrophages, whereas in the intra-gestational phase, the M2 phenotype dominated. This is related to the immune response patterns mediated by Th2 lymphocytes, which are predominant during gestation. 304