Extracellular vesicles of Trypanosoma cruzi tissue-culture cell-derived trypomastigotes: Induction of physiological changes in non-parasitized culture cells

Abstract

Extracellular vesicles (EVs) are a diverse group of nanoparticles involved in intercellular communication under physiological and pathological conditions. Trypanosoma cruzi, the protozoan that causes Chagas disease, releases EVs that facilitate parasite invasion of the host cell, immunomodulate the host response, and help the parasite to evade this response. However, little is known about how the host cell is altered. In this work, we confirm that EVs of tissue-culture cell-derived trypomastigotes of the Pan4 strain increase cell parasitism. We also demonstrate that EVs affect cell permeability in Vero cells and cardiomyocytes and raise intracellular Ca2+ levels, altering the actin filaments and arresting the cell cycle at the G0/G1 phases. This work seeks to elucidate the way in which EVs influence certain aspects of the cell physiology that favour the establishment of this parasite inside the host cell. The incubation of cells with EVs of trypomastigotes of the Pan4 strain of T. cruzi induce a number of changes in the host cells that include a change in cell permeability and higher intracellular levels of Ca2+ that can alter the dynamics of the actin cytoskeleton and arrest the cell cycle at G0/G1 prior to the DNA synthesis necessary to complete mitosis. These changes aid the invasion of host cells and augment the percentage of cell parasitization.