Interactions between Trypanosoma cruzi Secreted Proteins and Host Cell Signaling Pathways

Abstract

Chagas disease is one of the prevalent neglected tropical diseases, affecting at least 6–7 million individuals in Latin America. It is caused by the protozoan parasite Trypanosoma cruzi, which is transmitted to vertebrate hosts by blood-sucking insects. After infection, the parasite invades and multiplies in the myocardium, leading to acute myocarditis that kills around 5% of untreated individuals. T. cruzi secretes proteins that manipulate multiple host cell signaling pathways to promote host cell invasion. The primary secreted lysosomal peptidase in T. cruzi is cruzipain, which has been shown to modulate the host immune response. Cruzipain hinders macrophage activation during the early stages of infection by interrupting the NF-kB P65 mediated signaling pathway. This allows the parasite to survive and replicate, and may contribute to the spread of infection in acute Chagas disease. Another secreted protein P21, which is expressed in all of the developmental stages of T. cruzi, has been shown to modulate host phagocytosis signaling pathways. The parasite also secretes soluble factors that exert effects on host extracellular matrix, such as proteolytic degradation of collagens. Finally, secreted phospholipase A from T. cruzi contributes to lipid modifications on host cells and concomitantly activates the PKC signaling pathway. Here, we present a brief review of the interaction between secreted proteins from T. cruzi and the host cells, emphasizing the manipulation of host signaling pathways during invasion.

Astrocyte Apoptosis and HIV Replication Are Modulated in Host Cells Coinfected with Trypanosoma cruzi

“…However, neither inactive nor active TS isoforms (data not shown) appear to propitiate the parasite detrimental effect on HIV replication in astrocytes. Considering that other parasite-secreted proteins may influence the immune response (Watanabe Costa et al, 2016 ), further research is deserved.…”

Role of Proteomics in the Study of Trypanosoma cruzi Biology

“…Thus, for comparison of the proteomic profiles of highly virulent and low-virulent cell lines of T. cruzi, the molecular bases of T. cruzi virulence will be established. For the T. cruzi secretome, different interactions among T. cruzi secreted proteins and host cell signaling pathways have been proposed [86]. However, the role of these proteins in virulence and modulation of the host immune system has not been shown experimentally.…”

Circulating T Follicular Helper Cell Abnormalities Associated to Different Clinical Forms of Chronic Chagas Disease

“…Several parasite proteins have been shown to promote parasite invasion, replication and survival (Watanabe Costa et al, 2016). These molecules might also subvert the complement system and favor intracellular parasite growth, thus hampering the development of parasite-specific innate and adaptive immune responses (Cardoso et al, 2016).…”