T-Cell Subpopulations Exhibit Distinct Recruitment Potential, Immunoregulatory Profile and Functional Characteristics in Chagas versus Idiopathic Dilated Cardiomyopathies
Chronic Chagas cardiomyopathy (CCC) is one of the deadliest cardiomyopathies known and the most severe manifestation of Chagas disease, which is caused by infection with the parasite Trypanosoma cruzi. Idiopathic dilated cardiomyopathies (IDC) are a diverse group of inflammatory heart diseases that...
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Frontiers Media S.A.
2022-02-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2022.787423/full |
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| author | Eula G. A. Neves Carolina C. Koh Thaiany G. Souza-Silva Lívia Silva Araújo Passos Lívia Silva Araújo Passos Ana Carolina C. Silva Teresiama Velikkakam Fernanda Villani Fernanda Villani Janete Soares Coelho Janete Soares Coelho Claudia Ida Brodskyn Andrea Teixeira Kenneth J. Gollob Kenneth J. Gollob Maria do Carmo P. Nunes Walderez O. Dutra Walderez O. Dutra Walderez O. Dutra |
| author_facet | Eula G. A. Neves Carolina C. Koh Thaiany G. Souza-Silva Lívia Silva Araújo Passos Lívia Silva Araújo Passos Ana Carolina C. Silva Teresiama Velikkakam Fernanda Villani Fernanda Villani Janete Soares Coelho Janete Soares Coelho Claudia Ida Brodskyn Andrea Teixeira Kenneth J. Gollob Kenneth J. Gollob Maria do Carmo P. Nunes Walderez O. Dutra Walderez O. Dutra Walderez O. Dutra |
| author_sort | Eula G. A. Neves |
| collection | DOAJ |
| description | Chronic Chagas cardiomyopathy (CCC) is one of the deadliest cardiomyopathies known and the most severe manifestation of Chagas disease, which is caused by infection with the parasite Trypanosoma cruzi. Idiopathic dilated cardiomyopathies (IDC) are a diverse group of inflammatory heart diseases that affect the myocardium and are clinically similar to CCC, often causing heart failure and death. While T-cells are critical for mediating cardiac pathology in CCC and IDC, the mechanisms underlying T-cell function in these cardiomyopathies are not well-defined. In this study, we sought to investigate the phenotypic and functional characteristics of T-cell subpopulations in CCC and IDC, aiming to clarify whether the inflammatory response is similar or distinct in these cardiomyopathies. We evaluated the expression of systemic cytokines, determined the sources of the different cytokines, the expression of their receptors, of cytotoxic molecules, and of molecules associated with recruitment to the heart by circulating CD4+, CD8+, and CD4-CD8- T-cells from CCC and IDC patients, using multiparameter flow cytometry combined with conventional and unsupervised machine-learning strategies. We also used an in silico approach to identify the expression of genes that code for key molecules related to T-cell function in hearts of patient with CCC and IDC. Our data demonstrated that CCC patients displayed a more robust systemic inflammatory cytokine production as compared to IDC. While CD8+ T-cells were highly activated in CCC as compared to IDC, CD4+ T-cells were more activated in IDC. In addition to differential expression of functional molecules, these cells also displayed distinct expression of molecules associated with recruitment to the heart. In silico analysis of gene transcripts in the cardiac tissue demonstrated a significant correlation between CD8 and inflammatory, cytotoxic and cardiotropic molecules in CCC transcripts, while no correlation with CD4 was observed. A positive correlation was observed between CD4 and perforin transcripts in hearts from IDC but not CCC, as compared to normal tissue. These data show a clearly distinct systemic and local cellular response in CCC and IDC, despite their similar cardiac impairment, which may contribute to identifying specific immunotherapeutic targets in these diseases. |
| first_indexed | 2024-12-13T11:28:36Z |
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| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-12-13T11:28:36Z |
| publishDate | 2022-02-01 |
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| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-f7782b0f1dfa4432bcdada9cfa7b64832022-12-21T23:48:04ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-02-01910.3389/fcvm.2022.787423787423T-Cell Subpopulations Exhibit Distinct Recruitment Potential, Immunoregulatory Profile and Functional Characteristics in Chagas versus Idiopathic Dilated CardiomyopathiesEula G. A. Neves0Carolina C. Koh1Thaiany G. Souza-Silva2Lívia Silva Araújo Passos3Lívia Silva Araújo Passos4Ana Carolina C. Silva5Teresiama Velikkakam6Fernanda Villani7Fernanda Villani8Janete Soares Coelho9Janete Soares Coelho10Claudia Ida Brodskyn11Andrea Teixeira12Kenneth J. Gollob13Kenneth J. Gollob14Maria do Carmo P. Nunes15Walderez O. Dutra16Walderez O. Dutra17Walderez O. Dutra18Department of Morphology, Cell-Cell Interactions Laboratory, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, BrazilDepartment of Morphology, Cell-Cell Interactions Laboratory, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, BrazilDepartment of Morphology, Cell-Cell Interactions Laboratory, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, BrazilDepartment of Morphology, Cell-Cell Interactions Laboratory, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, BrazilBrigham and Womens Hospital, Harvard University, Boston, MA, United StatesDepartment of Morphology, Cell-Cell Interactions Laboratory, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, BrazilDepartment of Morphology, Cell-Cell Interactions Laboratory, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, BrazilDepartment of Morphology, Cell-Cell Interactions Laboratory, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, BrazilMinas Gerais State University, Divinópolis, BrazilDepartment of Morphology, Cell-Cell Interactions Laboratory, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, BrazilEzequiel Dias Foundation, Belo Horizonte, BrazilGonçalo Moniz Research Center, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, BrazilRene Rachou Institute, Fundação Oswaldo Cruz (FIOCRUZ), Belo Horizonte, BrazilHospital Israelita Albert Einstein, São Paulo, BrazilInstituto Nacional de Ciência e Tecnologia em Doenças Tropicais, INCT-DT, Salvador, BrazilGraduate Program in Infectology and Tropical Medicine, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, BrazilDepartment of Morphology, Cell-Cell Interactions Laboratory, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, BrazilInstituto Nacional de Ciência e Tecnologia em Doenças Tropicais, INCT-DT, Salvador, BrazilGraduate Program in Infectology and Tropical Medicine, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, BrazilChronic Chagas cardiomyopathy (CCC) is one of the deadliest cardiomyopathies known and the most severe manifestation of Chagas disease, which is caused by infection with the parasite Trypanosoma cruzi. Idiopathic dilated cardiomyopathies (IDC) are a diverse group of inflammatory heart diseases that affect the myocardium and are clinically similar to CCC, often causing heart failure and death. While T-cells are critical for mediating cardiac pathology in CCC and IDC, the mechanisms underlying T-cell function in these cardiomyopathies are not well-defined. In this study, we sought to investigate the phenotypic and functional characteristics of T-cell subpopulations in CCC and IDC, aiming to clarify whether the inflammatory response is similar or distinct in these cardiomyopathies. We evaluated the expression of systemic cytokines, determined the sources of the different cytokines, the expression of their receptors, of cytotoxic molecules, and of molecules associated with recruitment to the heart by circulating CD4+, CD8+, and CD4-CD8- T-cells from CCC and IDC patients, using multiparameter flow cytometry combined with conventional and unsupervised machine-learning strategies. We also used an in silico approach to identify the expression of genes that code for key molecules related to T-cell function in hearts of patient with CCC and IDC. Our data demonstrated that CCC patients displayed a more robust systemic inflammatory cytokine production as compared to IDC. While CD8+ T-cells were highly activated in CCC as compared to IDC, CD4+ T-cells were more activated in IDC. In addition to differential expression of functional molecules, these cells also displayed distinct expression of molecules associated with recruitment to the heart. In silico analysis of gene transcripts in the cardiac tissue demonstrated a significant correlation between CD8 and inflammatory, cytotoxic and cardiotropic molecules in CCC transcripts, while no correlation with CD4 was observed. A positive correlation was observed between CD4 and perforin transcripts in hearts from IDC but not CCC, as compared to normal tissue. These data show a clearly distinct systemic and local cellular response in CCC and IDC, despite their similar cardiac impairment, which may contribute to identifying specific immunotherapeutic targets in these diseases.https://www.frontiersin.org/articles/10.3389/fcvm.2022.787423/fullT-cellscytokineschemokinesinflammationChagas cardiomyopathyidiopathic cardiomyopathy |
| spellingShingle | Eula G. A. Neves Carolina C. Koh Thaiany G. Souza-Silva Lívia Silva Araújo Passos Lívia Silva Araújo Passos Ana Carolina C. Silva Teresiama Velikkakam Fernanda Villani Fernanda Villani Janete Soares Coelho Janete Soares Coelho Claudia Ida Brodskyn Andrea Teixeira Kenneth J. Gollob Kenneth J. Gollob Maria do Carmo P. Nunes Walderez O. Dutra Walderez O. Dutra Walderez O. Dutra T-Cell Subpopulations Exhibit Distinct Recruitment Potential, Immunoregulatory Profile and Functional Characteristics in Chagas versus Idiopathic Dilated Cardiomyopathies Frontiers in Cardiovascular Medicine T-cells cytokines chemokines inflammation Chagas cardiomyopathy idiopathic cardiomyopathy |
| title | T-Cell Subpopulations Exhibit Distinct Recruitment Potential, Immunoregulatory Profile and Functional Characteristics in Chagas versus Idiopathic Dilated Cardiomyopathies |
| title_full | T-Cell Subpopulations Exhibit Distinct Recruitment Potential, Immunoregulatory Profile and Functional Characteristics in Chagas versus Idiopathic Dilated Cardiomyopathies |
| title_fullStr | T-Cell Subpopulations Exhibit Distinct Recruitment Potential, Immunoregulatory Profile and Functional Characteristics in Chagas versus Idiopathic Dilated Cardiomyopathies |
| title_full_unstemmed | T-Cell Subpopulations Exhibit Distinct Recruitment Potential, Immunoregulatory Profile and Functional Characteristics in Chagas versus Idiopathic Dilated Cardiomyopathies |
| title_short | T-Cell Subpopulations Exhibit Distinct Recruitment Potential, Immunoregulatory Profile and Functional Characteristics in Chagas versus Idiopathic Dilated Cardiomyopathies |
| title_sort | t cell subpopulations exhibit distinct recruitment potential immunoregulatory profile and functional characteristics in chagas versus idiopathic dilated cardiomyopathies |
| topic | T-cells cytokines chemokines inflammation Chagas cardiomyopathy idiopathic cardiomyopathy |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2022.787423/full |
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