Coinfecção por Trypanosoma cruzi e Leishmania (L.) amazonensis: um estudo da modulação da resposta imune in vivo e in vitro

Abstract

Co-infection with multiple parasites is a complex and under-investigated clinical reality in endemic areas. T. cruzi infection causes Chagas disease, a pathology with high cardiac tropism, while L. (L.) amazonensis causes cutaneous leishmaniasis, and both diseases coexist in several regions. Understanding the immunological interactions between these two pathogens is necessary for disease prognosis but remains largely unknown. Aiming to fill this gap, this study investigated the modulation of the immune response in vitro and in vivo models of co-infection, focusing on the progression of Chagas disease. We demonstrated that co-infection does not manifest as an additive process, but rather as a paradoxical interaction that results in a scenario of immunological dysregulation. In single infections, T. cruzi showed a superior replicative capacity over L. (L.) amazonensis in macrophages, highlighting its intrinsic proliferative capacity. However, the presence of L. (L.) amazonensis suppressed T. cruzi replication in isolated environments, while co-infection promoted a mixed M1/M2 macrophage polarization and a reduction in the expression of necessary inflammatory pathways. Paradoxically, this local modulation facilitates the systemic pathogenesis of T. cruzi, leading to a more severe disease outcome, with greater parasitic dissemination and an exacerbation of chagasic myocarditis. The immune response in the heart is characterized by excessive inflammation, possibly mediated by an increase in IL-6, which is nevertheless ineffective for parasite control due to the inhibition of iNOS expression. It was concluded that the immunological imbalance in co-infection contributes to the worsening of cardiomyopathy, reinforcing the importance of considering co-infections in the diagnosis and management of Chagas disease in co-endemic regions.