Project description:Trypanosoma cruzi is the protozoan that causes Chagas disease, an endemic parasitosis in Latin America that has spread around the globe. Recently, a series of studies indicate that the gastrointestinal tract represents an important reservoir for T. cruzi in the chronic phase. It is also known that, during contact between T. cruzi and host cells, there is a 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 these EVs is not understood. In this study, 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 T. cruzi culture-derived trypomastigotes (TCTs) belonging to two distinct strains (CL Brener, DTU Tc VI and Dm28c DTU Tc I) in contact with C2C12 and Caco-2 cells to 2 hours and after 24 hours of infection. The interaction of the parasite with the host cell induces a switch in the functionality of proteins carried by LEVs and a varied tissue answer. Protein-protein interaction analysis indicates that LEVs carry key proteins for host-pathogen interaction that could participate in the pathogenesis of Chagas Disease.
Project description:Whole genome sequencing of T. cruzi field isolates reveals extensive genomic variability and complex aneuploidy patterns within TcII DTU
Project description:As Trypanosoma cruzi, the etiological agent of Chagas disease, multiplies in the cytoplasm of nucleated host cells, infection with this parasite is highly likely to affect host cells. We performed an exhaustive transcriptome analysis of T. cruzi-infected HeLa cells using an oligonucleotide microarray containing probes for greater than 47,000 human gene transcripts. In comparison with uninfected cells, those infected with T. cruzi showed greater than threefold up-regulation of 41 genes and greater than threefold down-regulation of 23 genes. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) of selected, differentially expressed genes confirmed the microarray data. Many of these up- and down-regulated genes were related to cellular proliferation, including seven up-regulated genes encoding proliferation inhibitors and three down-regulated genes encoding proliferation promoters, strongly suggesting that T. cruzi infection inhibits host cell proliferation, which may allow more time for T. cruzi to replicate and produce its intracellular nests. These findings provide new insight into the molecular mechanisms by which intracellular T. cruzi infection influences the host cell, leading to pathogenicity. Keywords: infection response