Análise da infectividade e adaptação à invasão de diferentes tipos celulares por Trypanosoma cruzi

Abstract

Trypanosoma cruzi is the etiologic agent of Chagas disease, which affects more than 6 million people worldwide. T. cruzi, belonging to the Trypanosomatidae family, is an obligate intracellular parasite capable of infecting any nucleated cell of the mammalian host. A striking feature of the T. cruzi genome is the dramatic expansion of multigene families, many of which encode surface proteins expressed by infective trypomastigote forms, such as trans-sialidases, MASPs, and mucins. Although some members of these families have already been implicated in the cellular invasion process, no clear association between a specific profile of surface molecules and the parasite's ability to infect a particular host cell has yet been unraveled. To investigate the possible association between specific molecules of the parasite and the infection of different cells of the mammalian host, trypomastigote forms derived from the same initial population obtained from MEF cells (fibroblast) were used to infect L6 (myoblast) and LLCMK2 cells (epithelial cell) for fifteen sequential passages. We verified a higher infection rate in cells from which they were isolated when compared to the other cell types used, indicating the parasite's ability to optimize its infection to different host cells. To verify whether the sequential passage of the parasite in each of these host cells can select subpopulations of the parasite and/or configure a specific pattern of gene expression that optimizes infection rates, the DNA and RNA of trypomastigotes obtained after the sequential passages were sequenced. It was possible to observe changes in the pattern of aneuploidies and gene expression in the parasites according to the infected cell. Regarding gene expression, there is a difference in the number of positively regulated genes, in the proportion of multigene families that are expressed among isolated parasites of each cell type and in the hypothetical and already annotated genes. Besides that, we also evaluated motifs of multigene families that had high expression levels in each cell type and identified the peptides from these motifs.