Trypanosoma cruzi: Entry into Mammalian Host Cells and Parasitophorous Vacuole Formation

Abstract

Trypanosoma cruzi, the causative agent of Chagas disease, is transmitted to vertebrate hosts by blood-sucking insects. This protozoan is an obligate intracellular parasite. The infective forms of the parasite are the metacyclic trypomastigotes, amastigotes, and bloodstream trypomastigotes. The recognition between the parasite and mammalian host cell, involves numerous molecules present in both cell types, and similar to several intracellular pathogens, T. cruzi is internalized by host cells via multiple endocytic pathways. Morphological studies demonstrated that after the interaction of the infective forms of T. cruzi with phagocytic or non-phagocytic cell types, plasma membrane (PM) protrusions can form, showing similarity with those observed during canonical phagocytosis or macropinocytic events. Additionally, several molecules known to be molecular markers of membrane rafts, macropinocytosis, and phagocytosis have been demonstrated to be present at the invasion site. These events may or may not depend on the host cell lysosomes and cytoskeleton. In addition, after penetration, components of the host endosomal-lysosomal system, such as early endosomes, late endosomes, and lysosomes, participate in the formation of the nascent parasitophorous vacuole (PV). Dynamin, a molecule involved in vesicle formation, has been shown to be involved in the PV release from the host cell PM. This review focuses on the multiple pathways that T. cruzi can use to enter the host cells until complete PV formation. We will describe different endocytic processes, such as phagocytosis, macropinocytosis, and endocytosis using membrane microdomains and clathrin-dependent endocytosis and show results that are consistent with their use by this smart parasite. We will also discuss others mechanisms that have been described, such as active penetration and the process that takes advantage of cell membrane wound repair.

Altering the motility of Trypanosoma cruzi with rabbit polyclonal anti-peptide antibodies reduces infection to susceptible mammalian cells

“…cruzi cellular invasion initiates with the parasite's attachment to the cell membrane, followed by endocytosis and the formation of a parasitophorous vacuole (Barrias et al, 2013;de Souza et al, 2010;Romano et al, 2012). It is hypothesized that successful triggering of endocytosis is likely enhanced by sustained close apposition between the parasite and the target cell, which is in turn dependent on the trypomastigote's motility (Rodriguez et al, 1995).…”

“…After the parasite's apposition and attachment, cytoskeletal reorganization of the host cell is important for T. cruzi endocytosis in both phagocytic and non-phagocytic cells, as demonstrated by the inhibition of actin polymerization with cytochalasin D (Ferreira et al, 2006). Other internalization mechanisms such as caveolin-dependent endocytosis, also participate in T. cruzi infection (Barrias et al, 2013;Romano et al, 2012).…”

La respuesta inmunitaria adaptativa en la infección crónica por Trypanosoma cruzi

“…Aunque se han identificado algunos ligandos que el parásito utiliza para unirse a las células huéspedes, son múltiples las moléculas que participan en esta interacción (Magdesian, et al, 2001). Después de la unión a la membrana celular, se presenta la formación de la vacuola parasitofora, donde operan diferentes mecanismos de endocitosis (Barrias, et al, 2013). Una vez dentro de la célula, empieza la formación de los amastigotes, los cuales pasan de la vacuola al citoplasma y entran en contacto directo con los organelos de las células huéspedes (Ley, et al, 1990;de Souza, et al, 2010).…”

Experimental Chagas disease in Balb/c mice previously vaccinated with T. rangeli. II. The innate immune response shows immunological memory: Reality or fiction?

“…This infection is considered a worldwide health problem and is recognized by the WHO as one of the world's 13 neglected tropical diseases, affecting 16 million people in these countries with a lack of treatment options due to the absence of an effective vaccine (Hotez et al, 2006;Barrias et al, 2013). This parasite presents a complex life cycle that occurs in both vertebrate and invertebrate hosts.…”

“…In mammalian hosts, the the vacuole through their acidification. This allows the destruction of this vacuole containing the parasite, which makes it possible for the parasite to escape later into the cytoplasm (Barrias et al, 2013). Although several studies have been conducted in the field of pathogen and host cell interaction, the mechanisms involved, in recruitment and internalization, are not altogether clear (Maeda et al, 2012).…”