Análise da atividade de vesículas extracelulares de trypanosoma cruzi na modulação da biogênese de corpúsculos lipídicos e da resposta inflamatória in vitro

Abstract

During infection by the protozoan Trypanosoma cruzi, the immune response plays a crucial role in controlling parasite load and ensuring host survival. However, the parasite has developed sophisticated immune evasion mechanisms that promote its persistence and the progression to the chronic phase of the disease. Among these mechanisms, extracellular vesicles (EVs) from T. cruzi act as intercellular communication mediators, transporting functional molecules that interact with host cells and modulate the immune response in favor of the parasite. EVs are lipid bilayer-enclosed structures released into the extracellular environment, participating in both parasite-parasite and parasite-host interactions. Studies indicate that these nanostructures induce the formation of lipid bodies (LBs) and modulate the host immune response. However, the molecular mechanisms by which EVs regulate lipid metabolism and inflammatory responses remain unclear. In this study, we evaluated the role of EVs derived from trypomastigote forms of the T. cruzi DM28c strain in the activation of C2C12 cells. We analyzed the modulation of lipid metabolism, the production of pro-inflammatory cytokines such as TNF-α, IL-12, and IL-6, as well as the anti-inflammatory cytokine IL-10, and the impact of these EVs on the course of T. cruzi infection. The results indicated that EV stimulation of C2C12 cells promotes an increase in LB formation, an effect that is enhanced in the presence of T. cruzi infection after 24 hours. Furthermore, EVs induced a reduction in the production of pro-inflammatory cytokines (IL-12, TNF-α, and IL-6), an effect intensified when cells were simultaneously exposed to both EVs and the parasite. Conversely, we observed a increase in IL-10 production in the presence of EVs, a phenomenon amplified during infection. These findings suggest that T. cruzi-derived EVs exert an immunomodulatory role, favoring parasite survival by suppressing pro-inflammatory cytokine production and stimulating IL-10 secretion. The immunomodulation induced by EVs, combined with the promotion of LB biogenesis, may contribute to the persistence of T. cruzi in the mammalian host, impacting the pathogenesis of Chagas disease.