Is It Possible to Intervene in the Capacity of Trypanosoma cruzi to Elicit and Evade the Complement System?

Abstract

Chagas’ disease is a zoonotic parasitic ailment now affecting more than 6 million people, mainly in Latin America. Its agent, the protozoan Trypanosoma cruzi, is primarily transmitted by endemic hematophagous triatomine insects. Transplacental transmission is also important and a main source for the emerging global expansion of this disease. In the host, the parasite undergoes intra (amastigotes) and extracellular infective (trypomastigotes) stages, both eliciting complex immune responses that, in about 70% of the cases, culminate in permanent immunity, concomitant with the asymptomatic presence of the parasite. The remaining 30% of those infected individuals will develop a syndrome, with variable pathological effects on the circulatory, nervous, and digestive systems. Herein, we review an important number of T. cruzi molecules, mainly located on its surface, that have been characterized as immunogenic and protective in various experimental setups. We also discuss a variety of parasite strategies to evade the complement system - mediated immune responses. Within this context, we also discuss the capacity of the T. cruzi infective trypomastigote to translocate the ER-resident chaperone calreticulin to its surface as a key evasive strategy. Herein, it is described that T. cruzi calreticulin inhibits the initial stages of activation of the host complement system, with obvious benefits for the parasite. Finally, we speculate on the possibility to experimentally intervene in the interaction of calreticulin and other T. cruzi molecules that interact with the complement system; thus resulting in significant inhibition of T. cruzi infectivity.

Vaccination with parasite-specific TcTASV proteins combined with recombinant baculovirus as a delivery platform protects against acute and chronic Trypanosoma cruzi infection

“…Vaccinated animals show a potent antibody response, with higher titers than those previously obtained in immunizations with rTcTASV-C adjuvanted with aluminum hydroxide, saponin, and/or U-Omp19 ( Caeiro et al., 2018 , 2020 ). In addition, functional antibodies triggered by vaccination contribute to the complement-mediated lysis of trypomastigotes, which is a desirable immune mechanism that interferes with the initial phase of infection ( Lidani et al., 2019 ; Ramírez-Toloza et al., 2021 ). The improvement in humoral response may be due to the already reported adjuvant capacity of the baculovirus ( Abe and Matsuura, 2010 ; Molina et al., 2021 ).…”

The End Justifies the Means: Chagas Disease from a Perspective of the Host–Trypanosoma cruzi Interaction

“…Trypanosoma cruzi has on its surface a wide range of molecules that interfere both in the initiation of the complement system pathways and in the assembly of C3 convertase. Among the important molecules for resistance to attack by the complement system are calreticulin TcCRT [46], TcCRP [47], TcCRIT [48], GP58/68 [49], and T-DAF [50], which are differentially expressed at different stages and by different strains of the parasite [51]. Furthermore, the induction of the release of extracellular vesicles (EVs) by T. cruzi also participates in the inhibition of the complement system.…”

The therapeutic mavericks: Potent immunomodulating chaperones capable of treating human diseases

“… 45 More recently, work by Arturo Ferreira and his team have demonstrated that other parasites, particularly Tryanosoma cruzi , also present CRT on their cell surface to evade attack by the complement system. 46 This early work provoked an interest to study CRT—immune interactions further but did not explain how CRT cell surface expression was regulated either in humans or more primitive species.…”