Extracellular Vesicles Released by Trypanosoma cruzi: Roles in Host Interaction and Pathogenesis

Trypanosoma cruzi, the etiological agent of Chagas disease shedding extracellular vesicles (EVs) and modulate the parasite-host communication. These EV contain a diverse cargo of proteins, lipids, glycoconjugates, and nucleic acids that modulate host cell signaling pathways, immune responses, tissue tropism, and parasite persistence. Recent studies have demonstrated that EVs contribute to the establishment of infection by promoting parasite invasion, modulating inflammatory responses, and facilitating immune evasion. Furthermore, differences in EV composition among parasite populations with distinct virulence phenotypes suggest that these vesicles play a central role in disease progression and chronicity. Our research focuses on understanding the molecular mechanisms by which T. cruzi EVs influence hostpathogen interactions and contribute to pathogenesis. Through proteomic, transcriptomic, and functional analyses, we investigate how EV cargo affects host cell translation, cellular stress responses, inflammation, and tissue remodeling. Particular attention is given to the role of EV-associated nucleic acids in regulating gene expression in recipient cells and shaping the outcome of infection.In parallel, we showed that molecular pathways involved in EV biogenesis and function and CRISPRCas9 genome editing to generate targeted knockouts of genes associated with virulence, protein trafficking, ubiquitin-proteasome system components, and vesicle formation pathways. These genetically modified parasites enable the identification of key regulators controlling EV cargo selection, secretion, and biological activity. Combined with in vitro cellular models, organoid systems, and in vivo infection studies, these approaches provide unprecedented insights into the contribution of EVs to parasite adaptation, persistence, and host immune modulation.In conclusion, we are working in biology of T. cruzi EV and their role in Chagas disease pathogenesis, while identifying novel molecular targets for therapeutic intervention and biomarker discovery. 

This work was supported by Conselho Nac. Des. Cient. Tecnologico (CNPq 44/2024403388/2025-2-) and FAPESP (2020/07870-4).