Myocardial Gene Expression of T-bet, GATA-3, Ror- γ t, FoxP3, and Hallmark Cytokines in Chronic Chagas Disease Cardiomyopathy: An Essentially Unopposed TH1-Type Response

Abstract EN

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.