Avaliação da ação da IL-17 em macrófagos peritoneais murinos

Abstract

L. (L.) amazonensis is one of the species that cause American tegumentary leishmaniasis. Resistance to Leishmania infection is associated with Th1 lymphocytes, which produce IFN-γ and activate macrophages and promote the death of the parasites. However, during the infection, other T cells subtypes can develop, such as the Th17 subtype, which produce IL-17. The role of IL-17 is known in inflammatory diseases and infections with extracellular pathogens, and its function is associated to the migration and activation of neutrophils. In Leishmania infection, it is not clear whether this cytokine would influence the activation of a phenotype that controls infection. Aim: To assess whether IL-17 interferes with activation of murine macrophages and with their Leishmania amazonensis leishmanicidal. Methods: Thyoglycolate-elicited peritoneal macrophages from BALB/c or C57BL/6 mice were primed with IL-17, IFN-γ or IL-4, activated or not with lipopolysaccharide (LPS) and infected with L. (L.) amazonensis promastigotes. Culture supernatants were harvested 48 h after the stimulus to assess nitric oxide (NO) and IL-12p40 production. The cells were used to determine the phagocytic, leishmanicidal and arginase activity. Results: Macrophages from BALB/c and C57BL/6 mice stimulated with IL-17 and LPS produced IL-10 and increased arginase activity. IL-17 was not able to induce NO production by these cells, but promoted a small increase in IL-12p40 secretion by C57BL/6 mice macrophages. IL-17 favored the proliferation of Leishmania in macrophages from BALB/c mice, but not in C57BL/6 mice. A synergism was observed between IL-17 and IL-4 that increased IL-10 production and arginase activity in macrophages from BALB/c mice. In macrophages from C57BL/6 mice, however, a synergism was observed between IL-17 and IFN-γ in the stimulation of NO production. Conclusion: These results suggest that IL-17 may participate in the activation of macrophages toward either phenotype depending on the mouse strain. The finding that IL-17 impairs the control of L. (L.) amazonensis in BALB/c mice was not observed in C57BL/6 mice. IL-10 production in macrophages stimulated with IL-17 suggests a regulatory role of this last cytokine.