O papel da IL-32γ no controle e imunopatogênese da doença de Chagas experimental na fase aguda

Abstract

Chagas disease (CD) is an important parasitic disease caused by Trypanosoma cruzi (T. cruzi). The Cardiopathy is the principal pathological process in CD and affects 30% of infected individuals. The initial immune pathways is a determinant factor for disease pathogenesis. Proinflammatory cytokine production direct macrophage microbicidal mechanisms against T. cruzi. Described in 2005, IL-32 may have nine isoforms, which are generated by alternative splicing of IL-32γ mRNA. In general, IL-32 plays a pro-inflammatory role and induces other cytokines with the same profile, as well as polarizing the acquired immune response to a mixed Th1 / Th17 profile. Since then, the role of IL-32 in the control and/or immunopathogenesis of inflammatory and infectious diseases has been demonstrated. Although murine cells respond to this cytokine, there is no IL-32 homologous gene in mice. The objective of this study was to evaluate the influence of IL-32γ on the immune response profile and, consequently, on the pathogenesis of myocarditis in acute experimental Chagas disease. For this, C57Bl / 6 WT and IL-32γTg mice were infected with 1000 forms of the Colombian strain of T. cruzi. Survival and parasitemia were evaluated during the 28 days of infection. In the histopathological analyzes, T. cruzi nests, myocarditis and collagen were quantified in cardiac tissue. Cytokine production was measured in cardiac homogenate and supernatants of conA and AgTc-stimulated splenic cell cultures at 24 and 72h by ELISA. Body and heart weight were also evaluated. For histological analyzes, we observed a lower density of amastigote nest in the animals of the group IL-32γTg. Regarding cytokines in situ, infected WT and IL-32γTg mice showed similar levels of IFN-γ and IL-17, and among IL-32γTg mice IL-32γ production was maintained during this period. However, IL-10 was significantly more expressed in IL-32γTg. In splenic cells IL-17 production was not statistically different between infected groups, however IL-32γTg animals showed higher IL-10 and IFN-γ production. The cytokine profile found in IL-32γTg animals contributed to body weight maintenance, greater parasitemia control and survival. Our results indicate that the presence of IL-32γ in mice infected with the Colombian strain of T. cruzi is important for infection control during the acute phase of Chagas disease.