Myocardial gene expression of T-bet, GATA-3, Ror-γ t, FoxP3, and hallmark cytokines in chronic Chagas disease cardiomyopathy: An essentially unopposed T-Type response

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Abstract

Background. Chronic Chagas disease cardiomyopathy (CCC), a late consequence of Trypanosoma cruzi infection, is an inflammatory cardiomyopathy with prognosis worse than those of noninflammatory etiology (NIC). Although the T cell-rich myocarditis is known to play a pathogenetic role, the relative contribution of each of the functional T cell subsets has never been thoroughly investigated. We therefore assessed gene expression of cytokines and transcription factors involved in differentiation and effector function of each functional T cell subset (T H 1/ T H 2/ T H 17/Treg) in CCC, NIC, and heart donor myocardial samples. Methods and Results. Quantitative PCR showed markedly upregulated expression of IFN-γ and transcription factor T-bet, and minor increases of GATA-3; FoxP3 and CTLA-4; IL-17 and IL-18 in CCC as compared with NIC samples. Conversely, cytokines expressed by T H 2 cells (IL-4, IL-5, and IL-13) or associated with Treg (TGF-β and IL-10) were not upregulated in CCC myocardium. Expression of T H 1-related genes such as T-bet, IFN-γ, and IL-18 correlated with ventricular dilation, FoxP3, and CTLA-4. Conclusions. Results are consistent with a strong local T H 1-mediated response in most samples, possibly associated with pathological myocardial remodeling, and a proportionally smaller FoxP3+CTLA4+ Treg cell population, which is unable to completely curb IFN-γ production in CCC myocardium, therefore fueling inflammation.

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Nogueira, L. G., Santos, R. H. B., Fiorelli, A. I., Mairena, E. C., Benvenuti, L. A., Bocchi, E. A., … Cunha-Neto, E. (2014). Myocardial gene expression of T-bet, GATA-3, Ror-γ t, FoxP3, and hallmark cytokines in chronic Chagas disease cardiomyopathy: An essentially unopposed T-Type response. Mediators of Inflammation, 2014. https://doi.org/10.1155/2014/914326

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