Mechanisms of Trypanosoma cruzi persistence in Chagas disease

Abstract

Summary Trypanosoma cruzi infection leads to development of chronic Chagas disease. In this article, we provide an update on the current knowledge of the mechanisms employed by the parasite to gain entry into the host cells and establish persistent infection despite activation of a potent immune response by the host. Recent studies point to a number of T. cruzi molecules that interact with host cell receptors to promote parasite invasion of the diverse host cells. T. cruzi expresses an antioxidant system and thromboxane A2 to evade phagosomal oxidative assault and suppress the host’s ability to clear parasites. Additional studies suggest that besides cardiac and smooth muscle cells that are the major target of T. cruzi infection, adipocytes and adipose tissue serve as reservoirs from where T. cruzi can recrudesce and cause disease decades later. Further, T. cruzi employs at least four strategies to maintain a symbiotic-like relationship with the host, and ensure consistent supply of nutrients for its own survival and long-term persistence. Ongoing and future research will continue to help refining the models of T. cruzi invasion and persistence in diverse tissues and organs in the host.

Curcumin Enhances the Anti-Trypanosoma cruzi Activity of Benznidazole-Based Chemotherapy in Acute Experimental Chagas Disease

“…However, the presence of blood trypomastigotes or parasite DNA in cardiac tissue from some animals treated with this combination was still detected after immunosuppression, hemocultures, or PCR. Previous studies showed that although early treatment with Bz is effective at eliminating parasitemia, parasitological cure is not always achieved due to the presence of T. cruzi reservoirs resistant to chemotherapy, which are distributed throughout multiple organs and tissues (35,36). Thus, there is evidence that the efficiency of etiological treatment is directly influenced by multiple factors, especially the variable profiles of resistance to infection observed in different mouse strains (28,37), parasite virulence, and the different sensitivities of T. cruzi strains to Bz (9,38).…”

Interferon-γ and other inflammatory mediators in cardiomyocyte signaling during Chagas disease cardiomyopathy

“…The establishment of a long-term infection in the heart and the development of a cardiomyopathy condition are directly related to the ability of T. cruzi to infect and persist within cardiomyocytes during the acute phase of infection [33,34] . Cardiomyocytes are differentiated cells that respond to T.cruzi infection by initiating adaptive strategies.…”

Sensing parasites: Proteomic and advanced bio-detection alternatives

“…In this sense, the infection and persistence by protozoan parasites is associated with changes in host tissue protein composition, highlighting that both parasite and host-derived molecules modulate disease progression [113,115]. For instance, these kind of bidirectional protein signatures have been identified by proteomics in Plasmodium falciparum [116].…”