Pentachloropseudilin Treatment Impairs Host Cell Invasion by Trypanosoma cruzi.

Pentachloropseudilin (PClP) is a reversible and allosteric inhibitor of type 1 myosin. Here, we addressed the impact of PClP treatment of Trypanosoma cruzi and mammalian host cell on the parasite migration, cell adhesion and invasion. We observed that PClP was not toxic to either T. cruzi or host cell. Moreover, treatment of T. cruzi with PClP inhabited parasite motility, host cell adhesion and invasion. Treatment of host cell with PClP also impaired parasite invasion probably by decreasing lysosome migration to the entry site of the parasite. Therefore, PClP treatment impaired fundamental processes necessary for a successful T. cruzi infection.

The Recombinant Form of Trypanosoma cruzi P21 Controls Infection by Modulating Host Immune Response.

Trypanosoma cruzi P21 protein (P21) is a putative secreted and immunomodulatory molecule with potent bioactive properties such as induction of phagocytosis and actin cytoskeleton polymerization. Despite the bioactive properties described so far, the action of P21 on parasite replication in muscle cell lineage or T. cruzi parasitism during acute experimental infection is unclear. We observed that recombinant P21 (rP21) decreased the multiplication of T. cruzi in C2C12 myoblasts, phenomenon associated with greater actin polymerization and IFN-γ and IL-4 higher expression. During experimental infection, lower cardiac nests, inflammatory infiltrate and fibrosis were observed in mice infected and treated with rP21. These results were correlated with large expression of IFN-γ counterbalanced by high levels of IL-10, which was consistent with the lower cardiac tissue injury found in these mice. We have also observed that upon stress, such as that induced by the presence of the IFN-γ cytokine, T. cruzi produced more P21. The effect of P21 in controlling the replication of T. cruzi, may indicate an evolutionary mechanism of survival developed by the parasite. Thus, when subjected to different stress conditions, the protozoan produces more P21, which induces T. cruzi latency in the host organism, enabling the protozoan to evade the host's immune system.