Amastigote Synapse: The Tricks of Trypanosoma cruzi Extracellular Amastigotes

Abstract

To complete its life cycle within the mammalian host, Trypanosoma cruzi, the agent of Chagas’ disease, must enter cells. Trypomastigotes originating from the insect vector (metacyclic) or from infected cells (bloodstream/tissue culture-derived) are the classical infective forms of the parasite and enter mammalian cells in an actin-independent manner. By contrast, amastigotes originating from the premature rupture of infected cells or transformed from swimming trypomastigotes (designated extracellular amastigotes, EAs) require functional intact microfilaments to invade non-phagocytic host cells. Earlier work disclosed the key features of EA-HeLa cell interplay: actin-rich protrusions called ‘cups’ are formed at EA invasion sites on the host cell membrane that are also enriched in actin-binding proteins, integrins and extracellular matrix elements. In the past decades we described the participation of membrane components and secreted factors from EAs as well as the actin-regulating proteins of host cells involved in what we propose to be a phagocytic-like mechanism of parasite uptake. Thus, regarding this new perspective herein we present previously described EA-induced ‘cups’ as parasitic synapse since they can play a role beyond its architecture function. In this review, we focus on recent findings that shed light on the intricate interaction between extracellular amastigotes and non-phagocytic HeLa cells.

Trypanosoma cruzi Presenilin-Like Transmembrane Aspartyl Protease: Characterization and Cellular Localization

“…After transferrin binding, endosomes are delivered to reservosomes [ 67 ]. As amastigotes and epimastigotes are replicative forms, it would be expected that they would have a larger demand for molecules to sustain proliferation [ 68 ].…”

All Roads Lead to Cytosol: Trypanosoma cruzi Multi-Strategic Approach to Invasion

“…FAK inhibition was associated with ERK1/2 dephosphorylation and F-actin rearrangement, suggesting a crosstalk between this signaling cascade and the MEK/ERK pathway (Onofre et al, 2019). Likewise, the interaction between HeLa cells and EAs induced N-WASPdependent actin polymerization via PI3K/AKT and ERK but not SFK (Src family kinases) (Bonfim- Melo et al, 2018a). In opposition, previous works on cardiomyocytes have shown that Src was required for TCTs internalization (Melo et al, 2014).…”

“…Additionally, it has been shown that amastigotes represent 10% of the parasites circulating in the blood of infected animals during the acute phase of infection (Andrews et al, 1987). Extracellular amastigotes (EAs), originated from premature rupture of infected cells or transformed from BSTs, are also infective and can disseminate in the infected hosts (Walker et al, 2014;Bonfim-Melo et al, 2018a).…”

Trypanosoma Cruzi Presenilin-like Transmembrane Aspartyl Protease: Characterization and Cellular Localization

“…reservosomes [67]. As amastigotes and epimastigotes are replicative forms, it would be expected that they would have a larger demand for molecules to sustain proliferation [68].…”