Expressão de citocinas e quimiocinas e sua associação com a imunopatogenia da cardiopatia chagásica crônica

Abstract

Cytokines and chemokines play an important role in modulating immune response; however, their pattern of expression in short, medium, and long-terms throughout the chronic phase of Chagas disease (ChD) have never been elucidated. This study was designed to identify a composite set of biomarkers associated with morbidity and to investigate the pattern of cytokine and chemokine expression in ChD. It is one of the largest analyses involving large set of samples from a cohort of patients grouped as indeterminate form (IND, n=93) and Chagas cardiomyopathy (CARD, n=141). Healthy individuals (n=32) were also included as a control group (non-infected [NI]). Mean age of ChD patients was 46.83±9.97 years (range, 23-69 years), and 119 (51%) were male. The IND group presented substantially higher levels of IL-17 compared to the CARD group and the NI group. Moreover, a significant correlation was verified between lower levels of IL-17 and cardiac morbidity. Exploratory analysis of cytokine and chemokine networks in the CARD group revealed significant positive correlations amongst IFN- CXCL10 and CXCL9 CXCL10 as well as negative strong axes connecting IL-10 with CXCL9 and TNF-. By contrast, in the IND group was remarkable the presence of an overall multifaceted network with stronger connections between IL-10 and IL-17, and IL-10 and IFN- axes along when compared to the other groups. Additional analyses showed that higher levels of IFN-, TNF-, CXCL9, and CXCL-10 together with lower levels of IL-10 are also associated with worse left ventricular function in ChD. The machine learning algorithms assays pointed out IFN-, TNF-, IL-10, and IL-17 as putative immunological biomarkers in ChD. No pattern could be observed when evaluating the IL-10 and IFN- expression in the IND group. On the other hand, these cytokines proved to be stable in the CARD group. All together, this study revealed a stable pattern of cytokine and chemokine expression troughout the chronic infection with T. cruzi and also their association with morbidity in ChD.