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
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 co...
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| Format: | Article |
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Wiley
2014-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2014/914326 |
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| author | Luciana Gabriel Nogueira Ronaldo Honorato Barros Santos Alfredo Inácio Fiorelli Eliane Conti Mairena Luiz Alberto Benvenuti Edimar Alcides Bocchi Noedir Antonio Stolf Jorge Kalil Edecio Cunha-Neto |
| author_facet | Luciana Gabriel Nogueira Ronaldo Honorato Barros Santos Alfredo Inácio Fiorelli Eliane Conti Mairena Luiz Alberto Benvenuti Edimar Alcides Bocchi Noedir Antonio Stolf Jorge Kalil Edecio Cunha-Neto |
| author_sort | Luciana Gabriel Nogueira |
| collection | DOAJ |
| description | 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 (TH1/TH2/TH17/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 TH2 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 TH1-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 TH1-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. |
| format | Article |
| id | doaj-art-081ca3558a9e44cdb3dfd9abdabca5af |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-081ca3558a9e44cdb3dfd9abdabca5af2025-02-03T06:07:04ZengWileyMediators of Inflammation0962-93511466-18612014-01-01201410.1155/2014/914326914326Myocardial Gene Expression of T-bet, GATA-3, Ror-γt, FoxP3, and Hallmark Cytokines in Chronic Chagas Disease Cardiomyopathy: An Essentially Unopposed TH1-Type ResponseLuciana Gabriel Nogueira0Ronaldo Honorato Barros Santos1Alfredo Inácio Fiorelli2Eliane Conti Mairena3Luiz Alberto Benvenuti4Edimar Alcides Bocchi5Noedir Antonio Stolf6Jorge Kalil7Edecio Cunha-Neto8Laboratory of Immunology, Heart Institute (InCor), University of São Paulo School of Medicine, 05403-000 São Paulo, SP, BrazilDivision of Surgery, Heart Institute (InCor), University of São Paulo School of Medicine, 05403-000 São Paulo, SP, BrazilDivision of Surgery, Heart Institute (InCor), University of São Paulo School of Medicine, 05403-000 São Paulo, SP, BrazilLaboratory of Immunology, Heart Institute (InCor), University of São Paulo School of Medicine, 05403-000 São Paulo, SP, BrazilDivision of Pathology, Heart Institute (InCor), University of São Paulo School of Medicine, 05403-000 São Paulo, SP, BrazilTransplantation and Heart Failure Unit, Heart Institute (InCor), University of São Paulo School of Medicine, 05403-000 São Paulo, SP, BrazilDivision of Surgery, Heart Institute (InCor), University of São Paulo School of Medicine, 05403-000 São Paulo, SP, BrazilLaboratory of Immunology, Heart Institute (InCor), University of São Paulo School of Medicine, 05403-000 São Paulo, SP, BrazilLaboratory of Immunology, Heart Institute (InCor), University of São Paulo School of Medicine, 05403-000 São Paulo, SP, BrazilBackground. 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 (TH1/TH2/TH17/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 TH2 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 TH1-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 TH1-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.http://dx.doi.org/10.1155/2014/914326 |
| spellingShingle | Luciana Gabriel Nogueira Ronaldo Honorato Barros Santos Alfredo Inácio Fiorelli Eliane Conti Mairena Luiz Alberto Benvenuti Edimar Alcides Bocchi Noedir Antonio Stolf Jorge Kalil Edecio Cunha-Neto 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 Mediators of Inflammation |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | http://dx.doi.org/10.1155/2014/914326 |
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