Myocardial Gene Expression of T-bet, GATA-3, Ror-γt, FoxP3, and Hallmark Cytokines in Chronic Chagas Disease Cardiomyopathy: An Essentially Unopposed TH1-Type Response. (24th July 2014)

• Record Type: Journal Article
• Authors: Nogueira, Luciana Gabriel; Santos, Ronaldo Honorato Barros; Fiorelli, Alfredo Inácio; Mairena, Eliane Conti; Benvenuti, Luiz Alberto; Bocchi, Edimar Alcides; Stolf, Noedir Antonio; Kalil, Jorge; Cunha-Neto, Edecio
• Other Names: Chevillard Christophe Academic Editor.
• Is Part Of: Mediators of inflammation. Volume 2014(2014)
• Publication Date: 2014-07-24
• Subjects: Inflammation -- Mediators -- Periodicals; Biological response modifiers -- Periodicals; Inflammation (Pathologie) -- Médiateurs; Immunomodulateurs; Biological response modifiers; Inflammation -- Mediators; Immunology; Autacoids; Immunologic Factors; Cell Adhesion Molecules; Cell Communication; Cytokines; Inflammation; Periodicals; Electronic journals; 616.0473
• DOI: 10.1155/2014/914326
• Languages: English
• ISSNs: 0962-9351

Abstract

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.