Avaliação do papel do fator de inibição da migração de macrófagos (MIF) na ativação de macrófagos peritoneais e de medula infectados por Toxoplasma gondii

Abstract

Introduction: Macrophages are immune cells with phagocytic activity that exhibit plasticity, acquiring phenotypes and functions depending on the microenvironment where they are found (MOLAWI et al., 2013). Cytokines are small molecules secreted by innumerous cells. Macrophage Migration Inhibitory Factor (MIF) is a cytokine initially described due to its function of inhibiting the random migration of macrophages. Currently, new functions have been described for MIF, such as stimulating inflammatory functions in response to infections by microorganisms, including Toxoplasma gondii. However, the primary function of MIF related to macrophages has been little addressed. Objective: Evaluate the possible participation of MIF in the differentiation processes of peritoneal and marrow macrophages from C57BL/6 WT and C57BL/6 MIF-/- male and female animals in response to T. gondii infection. Materials and Methods: Peritoneal macrophages were found from male and female C57BL/6 WT and MIF-/- mice after recruitment with thioglycolate. Bone marrow cells were collected for differentiation into macrophages. Peritoneal macrophages were treated with 4-Iodine-6-phenylpyrimidine (4-IPP) and infected or not with T.gondii for 24h. Then, the culture supernatant was collected for analysis of cytokines, urea and nitric oxide. Furthermore, macrophages were evaluated for phagocytic activity and rates of invasion and control of T. gondii. Results: The sex of C57BL6 mice influences the parasitism of peritoneal and marrow macrophages, as the parasite invades and proliferates more in macrophages derived from female mice. T.gondii infection triggered an increase in MIF production in the WT group, as well as an increase in the duo of IL-10, TNF, IFN-ƴ, IL-6 and IL-17 in WT and MIF-/- macrophages. Regarding the comparison between groups, it was detected that MIF-/- macrophages secreted more IL-10 compared to WT, on the other hand, WT macrophages produced greater amounts of TNF, IFN-ƴ, IL-6 and IL- 17. Urea production was more evident in MIF-/- macrophages while nitric oxide production was greater in WT macrophages. T. gondii showed greater spectrum capacity in MIF-/- macrophages, these cells also showed increased phagocytic activity. Conclusion: T. gondii infection induces the activation of macrophages derived from female mice, stimulating the production of cytokines. In the presence of MIF, T. gondii-infected macrophages produce pro-inflammatory cytokines compatible with the M1 activation profile. The absence of MIF caused a significant reduction in pro-inflammatory cytokines that are balanced by increased levels of urea and anti-inflammatory cytokines. These macrophages had increased phagocytic capacity and activation of features shared with the M2 profile.