The entire cycle of T. cruzi develops in two types of hosts, the mammalians of seven different orders including humans (vertebrate hosts) and several species of triatomine vectors (invertebrate host) from the Hemiptera order, Reduviidae family.
Biology in the vertebrate host
All T. cruzi stages are able to interact with vertebrate cells (Fig. 16.4A). However, only some parasites remain adherent to the cells and the level of adhesion is strain- dependent. Several studies show that each infective form, but also the strain and parasite phylogeny, will determine the outcome of this interaction.11,12 The establishment of the infection depends on a series of events involving interactions of diverse parasite’ molecules with host cell components. In this process, several glycoproteins, proteins with lectin activities present in both parasites and cells, are involved.
Yoshida13 showed that the penetration into the cell is particularly facilitated when the parasite presents surface glycoproteins with a higher gp82-kDa concentration, as observed with trypomastigotes of the CL strain. It has been observed that parasites with a predominance of gp90 and low levels of gp82 (G strain) show a very low ability to invade mammalian cells, whereas those with gp45 and gp50 display a moderate ability to infect these cells. More recently it was demonstrated that gp82-kDa of metacyclic forms has an essential role in host cell invasion and in the establishment of infection by oral route, whereas Tc85-11, which has affinity for laminin, would facilitate the parasite dissemination through diverse organs and tissues of the vertebrate host.14,15
With the metacyclic trypomastigotes, derivative forms of cellular culture, the internalization signal transduction pathways are activated both in parasite and host cells, leading to Ca21 mobilization.16,17 Some important differences are observed among the different sources of the parasite (trypomastigotes of tissue culture, metacyclic trypomastigotes of acellular culture) or even with different T. cruzi strains.
Another important factor that participates in this interaction is sialic acid, also present in both parasite and host cells. In T. cruzi—macrophage interaction, the presence of sialic acid in the membrane of the trypomastigote hinders
Figure 16.4 Schematic view of the various phases of the interaction of Trypanosoma cruzi with vertebrate cells. (A) The parasite adheres to the host cell membrane; (B) internalization of the parasite via pseudopods or depression (C) of the cell surface; (D) parasite inside the parasitophorous vacuole and fusion with the lysosomes; (E) change in trypomastigote morphology and disintegration of the parasitophorous vacuole membrane; (F) amastigote free in the cytoplasm of the host cell; (G) multiplication of the amastigotes; (H) amastigote—trypomastigote differentiation process passing through the intermediate epimastigote stage; (I) trypomastigotes in the cytoplasm of the host cell; and (J) rupture of the host cell and release of trypomastigotes into the intercellular space9.
the interaction process, which is facilitated when parasites are treated to remove or block this component.18 The trypomastigote normally presents transialidase and neuramidase in its membrane, which facilitates its interaction with vertebrate cells. Parasites that have a higher concentration of these enzymes are more invasive for the mammalian cells. Curiously, the epimastigote form, the noninfective stage, presents low levels of sialic acid. In contrast, it was demonstrated that the presence of sialic acid in the host cell membrane is also important for its interaction with T. cruzi. More recently it was demonstrated that the level of active transialidase (aTS) or inactive transialidase (iTS) in the parasite is associated with the phylogenetic divergence of the parasite or different DTUs.19