Molecular and cellular mechanisms involved in the trypanosoma cruzi/host cell interplay

Abstract

SummaryThe protozoan parasite Trypanosoma cruzi has a complex bi-ological cycle that involves vertebrate and invertebrate hosts. In mammals, the infective trypomastigote form of this parasite can invade several cell types by exploiting phagocytic-like or non-phagocytic mechanisms depending on the class of cell involved. Morphological studies showed that when trypomastigotes contact macrophages, they induce the formation of plasma membrane protrusions that differ from the canonical phagocytosis that occurs in the case of noninfective epimastigotes. In contrast, when trypomastigotes infect epithelial or muscle cells, the cell surface is minimally modified, suggesting the induction of a different class of process. Lysosomal-dependent or -independent T. cruzi invasion of host cells are two different models that describe the molecular and cellular events activated during parasite entry into nonphagocytic cells. In this context, we have previously shown that induction of autophagy in host cells before infection favors T. cruzi invasion. Furthermore, we demonstrate that autophagosomes and the autophagosomal protein LC3 are recruited to the T. cruzi entry sites and that the newly formed T. cruzi parasitophorous vacuole has characteristics of an autophagolysosome. This review summarizes the current knowledge of the molecular and cellular mechanisms of T. cruzi invasion in nonphagocytic cells. Based on our findings, we propose a new model in which T. cruzi takes advantage of the up-regulation of autophagy during starvation to increase its successful colonization of host cells.

SolubleN-ethylmaleimide-sensitive factor attachment protein receptors required duringTrypanosoma cruziparasitophorous vacuole development

“…According to the SNARE model, it is expected that SNAREs involved in TcPV formation would be displayed on its limiting membrane as a result of fusion events (Bombardier & Munson, 2015). For this reason, we investigated the presence of three different v-SNAREs based on their role in trafficking pathways previously related with T. cruzi host cell entry (Romano et al, 2012).…”

“…Studies of the mechanism that allows trypomastigotes (Try), the infective stage of T. cruzi, reaching host cell lysosomes in nonprofessional phagocytic cells have disclosed different strategies (Romano et al, 2012). The first involves lysosomes exocytosis at the site of parasite attachment (Tardieux et al, 1992), suggesting that lysosomes provide the membrane required for TcPV formation.…”

Recently differentiated epimastigotes from Trypanosoma cruzi are infective to the mammalian host

“…Epimastigote and amastigote are the replicative stages of the insect vector and mammalian host (De Souza, 2002), respectively. Since its discovery by Carlos Chagas, more than a century ago, it has been assumed that epimastigotes are not infective to the mammalian host (Chagas, 1909;Romano et al, 2012). This paradigm is corroborated by the widely acknowledged fact that only the epimastigote stage is susceptible to the mammalian innate immunity system and can be killed by the complement system (Nogueira et al, 1975;Iida et al, 1989;Cestari et al, 2009;Cestari and Ramirez, 2010).…”

How Does the Main Infective Stage ofT. cruziEnter and Avoid Degradation in Host Cells? A Description of the Pathways and Organelles Involved on These Processes

“…This transport is dependent on the KIF 5 protein (a kinesin) [76]. More recently, Romano et al [77] have shown that an autophagic protein, LC3, would also be present in the PV membrane, also demonstrating that the induction of autophagy in the host cell (pharmacological or physiological) interferes with the mechanism of trypomastigote invasion. Autophagy mechanism also plays a protective role against T. cruzi infection in mice by activation of a host immune response [78].…”