Extracelular Vesicles in Chagas Disease: Host-Parasite Interaction In Vivo Model

Extracellular vesicles (EVs) release by Trypanosoma cruzi trypomastigotes modulate  host-parasite interactions and disease outcomes across different stages of the parasite's  life cycle. Our research investigates the immunomodulatory effects of EVs released by  the Y strain of T. cruzi trypomastigotes in a Chagas disease (CD) model. It also  investigates the potential of EVs for developing new CD therapies and compares the  effects of trypomastigotes with distinct virulence profiles. The protozoa parasite can  survive in tissue culture-infected cells, it decreases virulence in mice. In our study, we  successfully restored virulence in mice upon 20 consecutive passages. As a result, we  performed a comparison study, comparing the impact of EVs released by non-virulent  trypomastigotes maintained in vitro (P2) to virulent trypomastigotes maintained in vivo (P20). Our results suggest a new link between T. cruzi virulence and EV release. Infection  with trypomastigotes P20 and P2 revealed higher parasitemia and tissue parasitism in  P20-infected animals. EVs increase parasitism in the heart first, then the bladder,  intestine, and lungs Pretreatment with EVs from the P20 strain exacerbated these effects  compared to pre-treatment with P2 EVs or controls. In parallel, we investigated the  dynamic cellular uptake of PHK26-labeled EVs using ImageStreams system microscopy.  Both P2 and P20 EVs interacted immediately with human monocytes. Concurrently, we  employed qRT-PCR to examine cytokine and chemokine expression in THP-1 cells upon  incubation with P2 and P20 EVs. In conclusion, EVs released by virulent (P20) and non virulent (P2) parasites during their interactions with host cells and assess the impact on  immune response communication, providing a detailed understanding of the complex  interactions between protozoa parasite and host cells. This allows us to understand how  virulence factors influence different stages of Chagas disease.