Cytokine Profiling in Chagas Disease: Towards Understanding the Association with Infecting Trypanosoma cruzi Discrete Typing Units (A BENEFIT TRIAL Sub-Study)

Abstract

BackgroundChagas disease caused by the protozoan Trypanosoma cruzi is an important public health problem in Latin America. The immunological mechanisms involved in Chagas disease pathogenesis remain incompletely elucidated. The aim of this study was to explore cytokine profiles and their possible association to the infecting DTU and the pathogenesis of Chagas disease.Methods109 sero-positive T. cruzi patients and 21 negative controls from Bolivia and Colombia, were included. Flow cytometry assays for 13 cytokines were conducted on human sera. Patients were divided into two groups: in one we compared the quantification of cytokines between patients with and without chronic cardiomyopathy; in second group we compared the levels of cytokines and the genetic variability of T. cruzi. ResultsSignificant difference in anti-inflammatory and pro-inflammatory cytokines profiles was observed between the two groups cardiac and non-cardiac. Moreover, serum levels of IFN-γ, IL-12, IL-22 and IL-10 presented an association with the genetic variability of T.cruzi, with significant differences in TcI and mixed infections TcI/TcII.ConclusionExpression of anti-inflammatory and pro-inflammatory cytokines may play a relevant role in determining the clinical presentation of chronic patients with Chagas disease and suggests the occurrence of specific immune responses, probably associated to different T. cruzi DTUs.

Perturbed T Cell IL-7 Receptor Signaling in Chronic Chagas Disease

“…Fonseca et al (31) have also demonstrated increased mRNA for IL-7 and the CD132 chain of the IL-R in heart tissues from Chagas disease patients with severe cardiomyopathy, supporting a putative role for IL-7 in the alteration of IL-7R components in the chronic phase of T. cruzi infection. A role for IL-5 and IL-9 in the perturbation of the IL-7 signaling pathway cannot be ruled out since these cytokines have been also detected in sera from patients with chronic cardiomyopathy (32,33). In human HIV infection, impaired IL-7/IL-7R signaling was correlated with the levels of basal phosphorylation, viral load and activation status, which were reverted upon successful antiretroviral treatment (34,35).…”

Chagas disease: morbidity profile in an endemic area of Northeastern Brazil

“…It is possible that these changes may be associated with the wide geographical dispersion of homogeneous T. cruzi genotypes from different parasite sources and groups that have been identifi ed throughout the municipalities of RN (60) . As a result, the forms of chronic ChD seem to be directly associated with discrete typing units of T. cruzi, which might explain the observed differences in the expression of anti-infl ammatory and pro-infl ammatory cytokines, and the specifi c immune responses (61) . Furthermore, this variability may depend on tissue-specifi c responses and the intensities of the parasitism, infl ammatory response, and immune response (62) (63) .…”

IL-10 participates in the expansion and functional activation of CD8+ T cells during acute infection with Trypanosoma cruzi

“…Previous studies have shown that the differential capacity of C3H/ HeSnJ and C57BL/ 6J mouse strains to produce IL‐10 shapes susceptibility to T. cruzi infection . Among chronically infected individuals, decreased serum IL‐10 levels are involved in the switch from the anti‐inflammatory profile of asymptomatic patients to the pro‐inflammatory one of patients with cardiomyopathy . These and other studies have revealed the participation of this cytokine in delaying the onset of cardiac symptoms in chronically infected individuals .…”