Immunomodulation for the Treatment of Chronic Chagas Disease Cardiomyopathy: A New Approach to an Old Enemy

Abstract

Chagas disease is a parasitic infection caused by the intracellular protozoan Trypanosoma cruzi. Chronic Chagas cardiomyopathy (CCC) is the most severe manifestation of the disease, developed by approximately 20-40% of patients and characterized by occurrence of arrhythmias, heart failure and death. Despite having more than 100 years of discovery, Chagas disease remains without an effective treatment, especially for patients with CCC. Since the pathogenesis of CCC depends on a parasite-driven systemic inflammatory profile that leads to cardiac tissue damage, the use of immunomodulators has become a rational alternative for the treatment of CCC. In this context, different classes of drugs, cell therapies with dendritic cells or stem cells and gene therapy have shown potential to modulate systemic inflammation and myocarditis in CCC models. Based on that, the present review provides an overview of current reports regarding the use of immunomodulatory agents in treatment of CCC, bringing the challenges and future directions in this field.

Interleukin 10 Polymorphisms as Risk Factors for Progression to Chagas Disease Cardiomyopathy: A Case-Control Study and Meta-Analysis

“…Studies in various contexts proposed a protective role of high-levels of IL-10 against Chagas disease progression, as these levels can attenuate the inflammatory tissue damage elicited by persistent infection with the protozoa ( 19 – 24 ). The association between low levels of IL-10 production and progression Chagas disease cardiomyopathy described in this study provides a rationale for immunomodulatory treatments for chronic Chagas disease potentiating IL-10 driven immunomodulatory functions ( 11 ).…”

“…It is therefore necessary to understand the factors that mediate clinical progression of susceptible individuals. In this line, host´s immune response appears to play a central role in the development of CCC and recent studies are helping to differentiate protective responses from pathogenic ones (7)(8)(9)(10)(11).…”

Resveratrol and Curcumin for Chagas Disease Treatment—A Systematic Review

“…Studies show the involvement of the inflammatory and immunological pathways in the progress of the disease, functioning as mechanisms for controlling its manifestation without the total death of the parasites, which persist in the host organism at low levels or in a latent form [ 20 , 21 , 22 ]. This process promotes progressive pathological damage in organs such as the heart, esophagus, and colon, modifying the architecture and functionality of the affected organs, affecting the quality of life [ 20 , 21 , 22 ].…”

Platelets, Macrophages, and Thromboinflammation in Chagas Disease

“…Further details regarding the pathogenesis of chronic inflammation in CD can be found in excellent recent reviews. 8 , 44 …”

“…Further details regarding the pathogenesis of chronic inflammation in CD can be found in excellent recent reviews. 8,44 Parasympathetic and sympathetic dysfunction and microvascular impairments have been described to contribute to chronic CD pathology. 8 High incidence of ischemic stroke is frequently noted in CD patients, and prevalence of stroke was higher in CD patients than in the general population of Brazil.…”