Trypanosoma cruzi interaction with host tissues modulate the composition of large extracellular vesicles

INTRODUCTION: Trypanosoma cruzi is the protozoan that causes Chagas disease (CD), an endemic parasitosis in Latin America that has spread around the globe. The chronic phase of CD may progress to cardiac, digestive or neurological manifestations. The gastrointestinal tract represents an important reservoir for T. cruzi in the chronic phase. The contact between T. cruzi and host cells induces the release of extracellular vesicles (EVs) that modulates the immune system and enhances the infection, but the dynamics of secretion of host and parasite molecules through different tissues is not known. We hypothesized that the parasite differentially interacts with myoblast and intestinal epithelial cells to release EVs and that the content of these EVs could provide evidence of the function of EVs in the pathogenesis of Chagas Disease. METHODS AND MATERIALS: We used two cell lines to simulate the environments found by the parasite in the host: C2C12 cell, myoblast and Caco-2 cell, intestinal epithelium. We isolated large EVs (LEVs) from the interaction of culture-derived trypomastigotes (TCTs) of T. cruzi (CL Brener and Dm28c) in contact with C2C12 and Caco-2 cells for 2 hours and after 24 hours of infection. Peptides of LEV proteins analysed by mass spectrometry and raw data from the LC-MS/MS runs were analysed in the MaxQuant platform. RESULTS AND CONCLUSIONS: Our data showed that at two hours there is a strong cellular response mediated by EVs, both in the number, variety and enrichment/targeting of proteins found in LEVs for diverse functions. Qualitative and quantitative analysis showed that proteins exported in LEVs of C2C12 and Caco-2 have different patterns. We found a predominance of host proteins at early infection. The parasite-host cell interaction induces a switch in the functionality of proteins carried by LEVs and a heterogeneous response depending on the tissues analysed. Protein–protein interaction analysis showed that cytoplasmic and mitochondrial homologues of the same parasite protein, tryparedoxin peroxidase, were differentially packaged in LEVs, also impacting the interacting molecule of this protein in the host. These data provide new evidence that the interaction with T. cruzi leads to a rapid tissue response through the release of LEVs, reflecting the enrichment of some proteins that could modulate the infection environment. FINANCIAL SUPPORT: Capes, CNPQ, Fiocruz.