PL4 - Plenary lecture 4

Extracellular Vesicles shed from Trypanosoma cruzi modulate immune response and host interaction

Torrecilhas, Ana Claudia ¹ - Schenkman, Sergio ²

1) Universidade Federal de São Paulo (UNIFESP); Instituto de Ciências Ambientais, Químicas e Farmacêuticas
2) Departamento de Microbiologia, Imunologia e Parasitologia, UNIFESP, São Paulo, Brazil
Contacto: ana.torrecilhas@unifesp.br

Trypanosoma cruzi, the protozoan parasite that causes Chagas disease, spontaneously releases extracellular vesicles (EVs) that are required for communication with both vertebrate and invertebrate hosts. EVs significantly improve the activation of the host immune system via TLR2-dependent signaling, promote parasite-host cell interactions, and increase cellular parasite invasion. In animal model infection, EVs increased parasitemia and parasite load in tissues.

Proteomic analysis identified gp85/trans-sialidase (TS) superfamily proteins, many of which are GPI-anchored and may play roles in receptor activation, cell attachment, and increased infection. Our results also indicate the presence of two unique particle types released by the parasite, implying functional heterogeneity among the EVs. Utilizing CRISPR-Cas9 technology (ESCRT Family), we observed that knockout parasites demonstrate a significant decrease in EV shedding from the parasite, suggesting that particle genes are essential for vesicle synthesis or secretion. Moreover, the virulent T. cruzi strain demonstrated efficacy in increasing tissue parasitism and immunological activation than the non-virulent strain. In conclusion, the particles are an essential function of T. cruzi and affect host-pathogen interactions, and highlight their potential as targets for therapeutic or diagnostic strategies in Chagas disease.