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

amage. 158 A study focused on the hypoxic granuloma regions in tuberculosis demonstrated that Arg1 expression seems to control M. tuberculosis growth when NOS2 is ineffective. In this case, enzyme expression correlates negatively with the proliferation of T cells. 149 Against leishmaniasis, stimuli presented to the same cells may or may not trigger the microbicidal response. 159, 160 Therefore, what is pertinent to the performance of TNF-α or IL-4 directly influences the formation of the M1/M2 phenotype. In vitro, for example, TNF-α inhibits IL-4induced Arg1 expression in bone marrow-derived macrophages. The consequences of this inactivation directly affect the phosphorylation and translocation of STAT6 to mediate production of Arg1. 161 In vivo Leishmania infections mainly show that in C57BL/6WT, the control of the cellular and microbicidal stress response is regulated by NOS2 and Arg1 with a predominance of NOS2 and NO. In the case of C57BL/6WT TNF −/-BALB/c, this change favors pathogen survival as well as non-phenotype change and a balanced expression of NOS2 and Arg1. 161 In Tie2Cre ± Arg fl/fl mice, the amastigote forms of Leishmania major are destroyed in activated macrophages where the inflammatory response is accentuated. In light of this, we conclude that the expression of TNF-α influences change in the cellular phenotype and potentiates the response of M1 macrophages in situ by Arg1 deletion, histone acetylation, and NOS2 and NO production. Interestingly, deletion of Arg1 can restore control of parasite proliferation in animals that evolved resistance. 161