Cellular invasion and formation of the parasitophorous vacuole
Trypomastigotes enter host cells by three distinct mechanisms (Fig. 16.4B and C), two of them involving an early interaction with host cell lysosomes.
- 1. The first mechanism is mediated by a direct fusion of lysosomes with the plasma membrane at the parasite’s attachment site, a process that originates the parasitophorous vacuole (PV)20 (Fig. 16.4D), which may comprise the host cell plasma membrane, either endosomal or lysosomal components.
- 2. The second mechanism observed is the invagination of the plasma membrane, without participation of the host cell actin cytoskeleton. In this case, the PV contains plasma membrane markers that rapidly mature by fusing with lysosomes (Fig. 16.4D). This early fusion of the vacuole with the lysosome is critical for retaining the trypomastigotes inside host cells, further transformations, and replication. An important event during the first and second mechanism of cellular invasion is the release of Ca21 ions from the parasite and host cells, which, together with lysosomes, migrate closer to the PV mem- brane.21,22 Thus, the process of cellular invasion by T. cruzi is considered a particular type of endocytosis for the epimastigote or phagocytosis for the trypomastigotes. Thus, the invasion of macrophages by epimastigotes involves the polymerization of actin and formation of pseudopodes. This process is strongly blocked when the parasites or macrophages are treated with cytochalasin, which is not observed with nonphagocytic cells.
- 3. The third mechanism of parasite cell interaction that occurs with the nonphagocytic cells in contrast, undergo a process of proteins phosphorylation with participation of phosphoi- nositide 3-kinase23 from the parasite and host cell. This last mechanism is a lysosome- independent pathway.
Subsequently to all these mechanisms of parasite—cell interaction and with the parasite in the PV, it maturates and acquires the early endossomic and lysosomic markers.