The Unsolved Jigsaw Puzzle of the Immune Response in Chagas Disease

Abstract

Trypanosoma cruzi interacts with the different arms of the innate and adaptive host's immune response in a very complex and flowery manner. The history of host-parasite co-evolution has provided this protozoan with means of resisting, escaping or subverting the mechanisms of immunity and establishing a chronic infection. Despite many decades of research on the subject, the infection remains incurable, and the factors that steer chronic Chagas disease from an asymptomatic state to clinical onset are still unclear. As the relationship between T. cruzi and the host immune system is intricate, so is the amount and diversity of scientific knowledge on the matter. Many of the mechanisms of immunity are fairly well understood, but unveiling the factors that lead each of these to success or failure, within the coordinated response as a whole, requires further research. The intention behind this Review is to compile the available information on the different aspects of the immune response, with an emphasis on those phenomena that have been studied and confirmed in the human host. For ease of comprehension, it has been subdivided in sections that cover the main humoral and cell-mediated components involved therein. However, we also intend to underline that these elements are not independent, but function intimately and concertedly. Here, we summarize years of investigation carried out to unravel the puzzling interplay between the host and the parasite.

Correlation of Parasite Burden, kDNA Integration, Autoreactive Antibodies, and Cytokine Pattern in the Pathophysiology of Chagas Disease

“…The investigation of immune response elements such as systemic cytokine levels greatly contributes toward disease comprehension, since cytokines are the main signaling molecules in this scenario. During early infection, high parasitemia resulted in activation of pro inflammatory response with high levels of TNF and IFN-γ being detected and corroborating the host attempt to eliminate the high parasite burden (Basso, 2013; Acevedo et al, 2018). The marked reduction in the systemic pro inflammatory cytokine dosage during the chronic phase of infection suggests that the exacerbated production of cytokines would not be the booster of CD pathogenesis, as proposed by the bystander activation theory (Gironès et al, 2005).…”

Effects of ghrelin supplementation on the acute phase of Chagas disease in rats

“…The initial phase of T. cruzi infection triggers several mechanisms of the innate response, such as nitric oxide production and activation of antigen-presentation (APCs) and NK cells [49]. The nitric oxide (NO) produced by macrophages has a pivotal anti- T. cruzi effect also observed in several infections caused by viruses, bacteria, fungi and protozoans [50].…”

Trypanosoma cruziInfection: Mechanisms of Evasion of Immune Response

“…In addition to the high variability of parasite surface antigens, parasite-derived B cell mitogens also cause polyclonal B cell activation and hypergammaglobulinemia which results in a delayed parasite-specific antibody response [108,124,125]. Glutamate dehydrogenase (TcGDH) [126], proline racemase [127], and trans-sialidase (TcTS) [128] are among the parasitic proteins identifying as polyclonal B cell mitogens [129].…”