Polymorphisms in Genes Affecting Interferon-γ Production and Th1 T Cell Differentiation Are Associated With Progression to Chagas Disease Cardiomyopathy
Background: Chagas disease, caused by the protozoan Trypanosoma cruzi, is endemic in Latin America. Thirty percent of infected individuals develop chronic Chagas cardiomyopathy (CCC), an inflammatory dilated cardiomyopathy that is the most important clinical consequence of T. cruzi infection, while...
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Frontiers Media S.A.
2020-07-01
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Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.01386/full |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Amanda Farage Frade-Barros Amanda Farage Frade-Barros Amanda Farage Frade-Barros Amanda Farage Frade-Barros Amanda Farage Frade-Barros Barbara Maria Ianni Sandrine Cabantous Cristina Wide Pissetti Bruno Saba Hui Tzu Lin-Wang Paula Buck José Antonio Marin-Neto André Schmidt Fabrício Dias Mario Hiroyuki Hirata Marcelo Sampaio Abílio Fragata Alexandre Costa Pereira Eduardo Donadi Virmondes Rodrigues Jorge Kalil Jorge Kalil Jorge Kalil Christophe Chevillard Edecio Cunha-Neto Edecio Cunha-Neto Edecio Cunha-Neto |
spellingShingle |
Amanda Farage Frade-Barros Amanda Farage Frade-Barros Amanda Farage Frade-Barros Amanda Farage Frade-Barros Amanda Farage Frade-Barros Barbara Maria Ianni Sandrine Cabantous Cristina Wide Pissetti Bruno Saba Hui Tzu Lin-Wang Paula Buck José Antonio Marin-Neto André Schmidt Fabrício Dias Mario Hiroyuki Hirata Marcelo Sampaio Abílio Fragata Alexandre Costa Pereira Eduardo Donadi Virmondes Rodrigues Jorge Kalil Jorge Kalil Jorge Kalil Christophe Chevillard Edecio Cunha-Neto Edecio Cunha-Neto Edecio Cunha-Neto Polymorphisms in Genes Affecting Interferon-γ Production and Th1 T Cell Differentiation Are Associated With Progression to Chagas Disease Cardiomyopathy Frontiers in Immunology Chagas disease cardiomyopathy susceptibility IL12 IL 10 IFN |
author_facet |
Amanda Farage Frade-Barros Amanda Farage Frade-Barros Amanda Farage Frade-Barros Amanda Farage Frade-Barros Amanda Farage Frade-Barros Barbara Maria Ianni Sandrine Cabantous Cristina Wide Pissetti Bruno Saba Hui Tzu Lin-Wang Paula Buck José Antonio Marin-Neto André Schmidt Fabrício Dias Mario Hiroyuki Hirata Marcelo Sampaio Abílio Fragata Alexandre Costa Pereira Eduardo Donadi Virmondes Rodrigues Jorge Kalil Jorge Kalil Jorge Kalil Christophe Chevillard Edecio Cunha-Neto Edecio Cunha-Neto Edecio Cunha-Neto |
author_sort |
Amanda Farage Frade-Barros |
title |
Polymorphisms in Genes Affecting Interferon-γ Production and Th1 T Cell Differentiation Are Associated With Progression to Chagas Disease Cardiomyopathy |
title_short |
Polymorphisms in Genes Affecting Interferon-γ Production and Th1 T Cell Differentiation Are Associated With Progression to Chagas Disease Cardiomyopathy |
title_full |
Polymorphisms in Genes Affecting Interferon-γ Production and Th1 T Cell Differentiation Are Associated With Progression to Chagas Disease Cardiomyopathy |
title_fullStr |
Polymorphisms in Genes Affecting Interferon-γ Production and Th1 T Cell Differentiation Are Associated With Progression to Chagas Disease Cardiomyopathy |
title_full_unstemmed |
Polymorphisms in Genes Affecting Interferon-γ Production and Th1 T Cell Differentiation Are Associated With Progression to Chagas Disease Cardiomyopathy |
title_sort |
polymorphisms in genes affecting interferon-γ production and th1 t cell differentiation are associated with progression to chagas disease cardiomyopathy |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2020-07-01 |
description |
Background: Chagas disease, caused by the protozoan Trypanosoma cruzi, is endemic in Latin America. Thirty percent of infected individuals develop chronic Chagas cardiomyopathy (CCC), an inflammatory dilated cardiomyopathy that is the most important clinical consequence of T. cruzi infection, while the others remain asymptomatic (ASY). IFN-γ and IFN-γ-producing Th1-type T cells are increased in peripheral blood and CCC myocardium as compared to ASY patients, while the Th1-antagonizing cytokine IL-10 is more expressed in ASY patients. Importantly IFN-γ-producing Th1-type T cells are the most frequent cytokine-producing T cell subset in CCC myocardium, while expression of Th1-antagonizing cytokines IL-10 and IL-4 is unaltered. The control of IFN-γ production by Th1-type T cells may be a key event for progression toward CCC. A genetic component to disease progression was suggested by the familial aggregation of cases and the association of gene polymorphisms with CCC development. We here investigate the role of gene polymorphisms (SNPs) in several genes involved in the control of IFN-γ production and Th1 T cell differentiation in CCC development.Methods: We studied a Brazilian population including 315 CCC cases and 118 ASY subjects. We assessed 35 Tag SNPs designed to represent all the genetic information contained in the IL12B, IL10, IFNG, and IL4 genes.Results: We found 2 IL12 SNPs (rs2546893, rs919766) and a trend of association for a IL10 SNP (rs3024496) to be significantly associated with the ASY group. these associations were confirmed by multivariate analysis and allele tests. The rs919766C, 12rs2546893G, and rs3024496C alleles were associated to an increase risk to CCC development.Conclusions: Our data show that novel polymorphisms affecting IL12B and IL10, but not IFNG or IL4 genes play a role in genetic susceptibility to CCC development. This might indicate that the increased Th1 differentiation and IFN-γ production associated with CCC is genetically controlled. |
topic |
Chagas disease cardiomyopathy susceptibility IL12 IL 10 IFN |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2020.01386/full |
work_keys_str_mv |
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doaj-6f1c3d5e1fec46f5879b05c7110b33832020-11-25T03:19:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-07-011110.3389/fimmu.2020.01386544583Polymorphisms in Genes Affecting Interferon-γ Production and Th1 T Cell Differentiation Are Associated With Progression to Chagas Disease CardiomyopathyAmanda Farage Frade-Barros0Amanda Farage Frade-Barros1Amanda Farage Frade-Barros2Amanda Farage Frade-Barros3Amanda Farage Frade-Barros4Barbara Maria Ianni5Sandrine Cabantous6Cristina Wide Pissetti7Bruno Saba8Hui Tzu Lin-Wang9Paula Buck10José Antonio Marin-Neto11André Schmidt12Fabrício Dias13Mario Hiroyuki Hirata14Marcelo Sampaio15Abílio Fragata16Alexandre Costa Pereira17Eduardo Donadi18Virmondes Rodrigues19Jorge Kalil20Jorge Kalil21Jorge Kalil22Christophe Chevillard23Edecio Cunha-Neto24Edecio Cunha-Neto25Edecio Cunha-Neto26Heart Institute (InCor), University of São Paulo School of Medicine (FMUSP), São Paulo, BrazilInstitute for Investigation in Immunology (iii), INCT, São Paulo, BrazilAix-Marseille Université, INSERM, GIMP UMR_S906, Marseille, FranceDivision of Clinical Immunology and Allergy, University of São Paulo School of Medicine, São Paulo, BrazilBioengineering Program, Instituto Tecnológico, Universidade Brasil, São Paulo, BrazilHeart Institute (InCor), University of São Paulo School of Medicine (FMUSP), São Paulo, BrazilAix-Marseille Université, INSERM, GIMP UMR_S906, Marseille, FranceLaboratory of Immunology, Universidade Federal Do Triângulo Mineiro (UFTM), Uberaba, BrazilLaboratório de Investigação Molecular em Cardiologia, Instituto de Cardiologia Dante Pazzanese (IDPC), São Paulo, BrazilLaboratório de Investigação Molecular em Cardiologia, Instituto de Cardiologia Dante Pazzanese (IDPC), São Paulo, BrazilHeart Institute (InCor), University of São Paulo School of Medicine (FMUSP), São Paulo, BrazilSchool of Medicine of Ribeirão Preto (FMRP), University of São Paulo, Ribeirão Preto, BrazilSchool of Medicine of Ribeirão Preto (FMRP), University of São Paulo, Ribeirão Preto, BrazilSchool of Medicine of Ribeirão Preto (FMRP), University of São Paulo, Ribeirão Preto, BrazilDepartment of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo (USP), São Paulo, BrazilLaboratório de Investigação Molecular em Cardiologia, Instituto de Cardiologia Dante Pazzanese (IDPC), São Paulo, BrazilLaboratório de Investigação Molecular em Cardiologia, Instituto de Cardiologia Dante Pazzanese (IDPC), São Paulo, BrazilHeart Institute (InCor), University of São Paulo School of Medicine (FMUSP), São Paulo, BrazilSchool of Medicine of Ribeirão Preto (FMRP), University of São Paulo, Ribeirão Preto, BrazilLaboratory of Immunology, Universidade Federal Do Triângulo Mineiro (UFTM), Uberaba, BrazilHeart Institute (InCor), University of São Paulo School of Medicine (FMUSP), São Paulo, BrazilInstitute for Investigation in Immunology (iii), INCT, São Paulo, BrazilBioengineering Program, Instituto Tecnológico, Universidade Brasil, São Paulo, Brazil0Aix Marseille Université, INSERM, TAGC Theories and Approaches of Genomic Complexity, UMR_1090, Marseille, FranceHeart Institute (InCor), University of São Paulo School of Medicine (FMUSP), São Paulo, BrazilInstitute for Investigation in Immunology (iii), INCT, São Paulo, BrazilDivision of Clinical Immunology and Allergy, University of São Paulo School of Medicine, São Paulo, BrazilBackground: Chagas disease, caused by the protozoan Trypanosoma cruzi, is endemic in Latin America. Thirty percent of infected individuals develop chronic Chagas cardiomyopathy (CCC), an inflammatory dilated cardiomyopathy that is the most important clinical consequence of T. cruzi infection, while the others remain asymptomatic (ASY). IFN-γ and IFN-γ-producing Th1-type T cells are increased in peripheral blood and CCC myocardium as compared to ASY patients, while the Th1-antagonizing cytokine IL-10 is more expressed in ASY patients. Importantly IFN-γ-producing Th1-type T cells are the most frequent cytokine-producing T cell subset in CCC myocardium, while expression of Th1-antagonizing cytokines IL-10 and IL-4 is unaltered. The control of IFN-γ production by Th1-type T cells may be a key event for progression toward CCC. A genetic component to disease progression was suggested by the familial aggregation of cases and the association of gene polymorphisms with CCC development. We here investigate the role of gene polymorphisms (SNPs) in several genes involved in the control of IFN-γ production and Th1 T cell differentiation in CCC development.Methods: We studied a Brazilian population including 315 CCC cases and 118 ASY subjects. We assessed 35 Tag SNPs designed to represent all the genetic information contained in the IL12B, IL10, IFNG, and IL4 genes.Results: We found 2 IL12 SNPs (rs2546893, rs919766) and a trend of association for a IL10 SNP (rs3024496) to be significantly associated with the ASY group. these associations were confirmed by multivariate analysis and allele tests. The rs919766C, 12rs2546893G, and rs3024496C alleles were associated to an increase risk to CCC development.Conclusions: Our data show that novel polymorphisms affecting IL12B and IL10, but not IFNG or IL4 genes play a role in genetic susceptibility to CCC development. This might indicate that the increased Th1 differentiation and IFN-γ production associated with CCC is genetically controlled.https://www.frontiersin.org/article/10.3389/fimmu.2020.01386/fullChagas diseasecardiomyopathysusceptibilityIL12IL 10IFN |