Genetic Polymorphism at CCL5 Is Associated With Protection in Chagas’ Heart Disease: Antagonistic Participation of CCR1+ and CCR5+ Cells in Chronic Chagasic Cardiomyopathy
| Autor(a) principal: | |
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| Data de Publicação: | 2018 |
| Outros Autores: | , , , , , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/25789 |
Resumo: | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ. Brasil. |
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Batista, Angelica MartinsAlvarado-Arnez, Lucia ElenaAlves, Silvia MarinhoMelo, GloriaPereira, Isabela ResendeRuivo, Leonardo Alexandre de SouzaSilva, Andrea Alice daGibaldi, DanielSilva, Thayse do E. S. Protásio daLorena, Virginia Maria Barros deMelo, Adriene Siqueira deSoares, Ana Karine de AraújoBarros, Michelle da SilvaCosta, Vláudia Mmaria AssisCardoso, Cynthia C.Pacheco, Antonio G.Carrazzone, CristinaOliveira Jr., WilsonMoraes, Milton OzórioLannes-Vieira, Joseli2018-04-12T11:27:35Z2018-04-12T11:27:35Z2018BATISTA, Angelica Martins et al. Genetic Polymorphism at CCL5 Is Associated With Protection in Chagas’ Heart Disease: Antagonistic Participation of CCR1+ and CCR5+ Cells in Chronic Chagasic Cardiomyopathy. Front. Immunol., v. 9, p. 1-16, Apr. 2018.1664-3224https://www.arca.fiocruz.br/handle/icict/2578910.3389/fimmu.2018.00615engFrontiers Mediahttps://www.arca.fiocruz.br/handle/icict/23621Doença de ChagasTrypanosoma cruziDoença do CoraçãoMovimento CelularChagas DiseaseTrypanosoma cruziheart diseasecell migrationCCL5CCR1CCRSMet-RANTESGenetic Polymorphism at CCL5 Is Associated With Protection in Chagas’ Heart Disease: Antagonistic Participation of CCR1+ and CCR5+ Cells in Chronic Chagasic Cardiomyopathyinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ. Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ. Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Ambulatório de Doença de Chagas e Insuficiência Cardíaca do Pronto Socorro Cardiológico de Pernambuco. Recife, PE, Brasil.Ambulatório de Doença de Chagas e Insuficiência Cardíaca do Pronto Socorro Cardiológico de Pernambuco. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ. Brasil.Universidade Federal Fluminense. Faculdade de Medicina. Departamento de Patologia. Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas. Niterói, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de Imunologia. Laboratório de Imunoparasitologia. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de Imunologia. Laboratório de Imunoparasitologia. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de Imunologia. Laboratório de Imunoparasitologia. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de Imunologia. Laboratório de Imunoparasitologia. Recife, PE, Brasil.Universidade Federal de Pernambuco. Departamento de Medicina Tropical. Recife, PE, Brasil / Universidade Federal de Pernambuco. Laboratório de Imunopatologia Keizo Asami. Recife, PE, Brasil.Universidade Federal do Rio de Janeiro. Departamento de Genética. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Presidência. Programa de Computação Científica. Rio de Janeiro, RJ, Brasil.Ambulatório de Doença de Chagas e Insuficiência Cardíaca do Pronto Socorro Cardiológico de Pernambuco. Recife, PE, Brasil.Ambulatório de Doença de Chagas e Insuficiência Cardíaca do Pronto Socorro Cardiológico de Pernambuco. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ. Brasil.Chronic cardiomyopathy is the main clinical manifestation of Chagas disease (CD), a disease caused by Trypanosoma cruzi infection. A hallmark of chronic chagasic cardiomyopathy (CCC) is a fibrogenic inflammation mainly composed of CD8+ and CD4+ T cells and macrophages. CC-chemokine ligands and receptors have been proposed to drive cell migration toward the heart tissue of CD patients. Single nucleotide polymorphisms (SNPs) in CC-chemokine ligand and receptor genes may determine protein expression. Herein, we evaluated the association of SNPs in the CC-chemokines CCL2 (rs1024611) and CCL5 (rs2107538, rs2280788) and the CCL5/RANTES receptors CCR1 (rs3181077, rs1491961, rs3136672) and CCR5 (rs1799987) with risk and progression toward CCC. We performed a cross-sectional association study of 406 seropositive patients from endemic areas for CD in the State of Pernambuco, Northeast Brazil. The patients were classified as non-cardiopathic (A, n = 110) or cardiopathic (mild, B1, n = 163; severe, C, n = 133). Serum levels of CCL5 and CCL2/MCP-1 were elevated in CD patients but were neither associated with risk/severity of CCC nor with SNP genotypes. After logistic regression analysis with adjustment for the covariates gender and ethnicity, CCL5 −403 (rs2107538) CT heterozygotes (OR = 0.5, P-value = 0.04) and T carriers (OR = 0.5, P-value = 0.01) were associated with protection against CCC. To gain insight into the participation of the CCL5–CCR5/CCR1 axis in CCC, mice were infected with the Colombian T. cruzi strain. Increased CCL5 concentrations were detected in cardiac tissue. In spleen, frequencies of CCR1+ CD8+ T cells and CD14+ macrophages were decreased, while frequencies of CCR5+ cells were increased. Importantly, CCR1+CD14+ macrophages were mainly IL-10+, while CCR5+ cells were mostly TNF+. CCR5-deficient infected mice presented reduced TNF concentrations and injury in heart tissue. Selective blockade of CCR1 (Met-RANTES therapy) in infected Ccr5−/− mice supported a protective role for CCR1 in CCC. Furthermore, parasite antigen stimulation of CD patient blood cells increased the frequency of CCR1+CD8+ T cells and CCL5 production. Collectively, our data support that a genetic variant of CCL5 and CCR1+ cells confer protection against Chagas heart disease, identifying the CCL5-CCR1 axis as a target for immunostimulation.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/25789/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALjoselilannes2_vieira_etal_IOC_2018.pdfjoselilannes2_vieira_etal_IOC_2018.pdfapplication/pdf2737835https://www.arca.fiocruz.br/bitstream/icict/25789/2/joselilannes2_vieira_etal_IOC_2018.pdf5a14821aaf12a2de79b739e8b2806eeaMD52TEXTjoselilannes2_vieira_etal_IOC_2018.pdf.txtjoselilannes2_vieira_etal_IOC_2018.pdf.txtExtracted texttext/plain91985https://www.arca.fiocruz.br/bitstream/icict/25789/3/joselilannes2_vieira_etal_IOC_2018.pdf.txta92b4de2b1bdc2aeb3d5fee23060070dMD53icict/257892022-06-24 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| dc.title.pt_BR.fl_str_mv |
Genetic Polymorphism at CCL5 Is Associated With Protection in Chagas’ Heart Disease: Antagonistic Participation of CCR1+ and CCR5+ Cells in Chronic Chagasic Cardiomyopathy |
| title |
Genetic Polymorphism at CCL5 Is Associated With Protection in Chagas’ Heart Disease: Antagonistic Participation of CCR1+ and CCR5+ Cells in Chronic Chagasic Cardiomyopathy |
| spellingShingle |
Genetic Polymorphism at CCL5 Is Associated With Protection in Chagas’ Heart Disease: Antagonistic Participation of CCR1+ and CCR5+ Cells in Chronic Chagasic Cardiomyopathy Batista, Angelica Martins Doença de Chagas Trypanosoma cruzi Doença do Coração Movimento Celular Chagas Disease Trypanosoma cruzi heart disease cell migration CCL5 CCR1 CCRS Met-RANTES |
| title_short |
Genetic Polymorphism at CCL5 Is Associated With Protection in Chagas’ Heart Disease: Antagonistic Participation of CCR1+ and CCR5+ Cells in Chronic Chagasic Cardiomyopathy |
| title_full |
Genetic Polymorphism at CCL5 Is Associated With Protection in Chagas’ Heart Disease: Antagonistic Participation of CCR1+ and CCR5+ Cells in Chronic Chagasic Cardiomyopathy |
| title_fullStr |
Genetic Polymorphism at CCL5 Is Associated With Protection in Chagas’ Heart Disease: Antagonistic Participation of CCR1+ and CCR5+ Cells in Chronic Chagasic Cardiomyopathy |
| title_full_unstemmed |
Genetic Polymorphism at CCL5 Is Associated With Protection in Chagas’ Heart Disease: Antagonistic Participation of CCR1+ and CCR5+ Cells in Chronic Chagasic Cardiomyopathy |
| title_sort |
Genetic Polymorphism at CCL5 Is Associated With Protection in Chagas’ Heart Disease: Antagonistic Participation of CCR1+ and CCR5+ Cells in Chronic Chagasic Cardiomyopathy |
| author |
Batista, Angelica Martins |
| author_facet |
Batista, Angelica Martins Alvarado-Arnez, Lucia Elena Alves, Silvia Marinho Melo, Gloria Pereira, Isabela Resende Ruivo, Leonardo Alexandre de Souza Silva, Andrea Alice da Gibaldi, Daniel Silva, Thayse do E. S. Protásio da Lorena, Virginia Maria Barros de Melo, Adriene Siqueira de Soares, Ana Karine de Araújo Barros, Michelle da Silva Costa, Vláudia Mmaria Assis Cardoso, Cynthia C. Pacheco, Antonio G. Carrazzone, Cristina Oliveira Jr., Wilson Moraes, Milton Ozório Lannes-Vieira, Joseli |
| author_role |
author |
| author2 |
Alvarado-Arnez, Lucia Elena Alves, Silvia Marinho Melo, Gloria Pereira, Isabela Resende Ruivo, Leonardo Alexandre de Souza Silva, Andrea Alice da Gibaldi, Daniel Silva, Thayse do E. S. Protásio da Lorena, Virginia Maria Barros de Melo, Adriene Siqueira de Soares, Ana Karine de Araújo Barros, Michelle da Silva Costa, Vláudia Mmaria Assis Cardoso, Cynthia C. Pacheco, Antonio G. Carrazzone, Cristina Oliveira Jr., Wilson Moraes, Milton Ozório Lannes-Vieira, Joseli |
| author2_role |
author author author author author author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Batista, Angelica Martins Alvarado-Arnez, Lucia Elena Alves, Silvia Marinho Melo, Gloria Pereira, Isabela Resende Ruivo, Leonardo Alexandre de Souza Silva, Andrea Alice da Gibaldi, Daniel Silva, Thayse do E. S. Protásio da Lorena, Virginia Maria Barros de Melo, Adriene Siqueira de Soares, Ana Karine de Araújo Barros, Michelle da Silva Costa, Vláudia Mmaria Assis Cardoso, Cynthia C. Pacheco, Antonio G. Carrazzone, Cristina Oliveira Jr., Wilson Moraes, Milton Ozório Lannes-Vieira, Joseli |
| dc.subject.other.pt_BR.fl_str_mv |
Doença de Chagas Trypanosoma cruzi Doença do Coração Movimento Celular |
| topic |
Doença de Chagas Trypanosoma cruzi Doença do Coração Movimento Celular Chagas Disease Trypanosoma cruzi heart disease cell migration CCL5 CCR1 CCRS Met-RANTES |
| dc.subject.en.pt_BR.fl_str_mv |
Chagas Disease Trypanosoma cruzi heart disease cell migration CCL5 CCR1 CCRS Met-RANTES |
| description |
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ. Brasil. |
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2018 |
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2018-04-12T11:27:35Z |
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2018-04-12T11:27:35Z |
| dc.date.issued.fl_str_mv |
2018 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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BATISTA, Angelica Martins et al. Genetic Polymorphism at CCL5 Is Associated With Protection in Chagas’ Heart Disease: Antagonistic Participation of CCR1+ and CCR5+ Cells in Chronic Chagasic Cardiomyopathy. Front. Immunol., v. 9, p. 1-16, Apr. 2018. |
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https://www.arca.fiocruz.br/handle/icict/25789 |
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1664-3224 |
| dc.identifier.doi.pt_BR.fl_str_mv |
10.3389/fimmu.2018.00615 |
| identifier_str_mv |
BATISTA, Angelica Martins et al. Genetic Polymorphism at CCL5 Is Associated With Protection in Chagas’ Heart Disease: Antagonistic Participation of CCR1+ and CCR5+ Cells in Chronic Chagasic Cardiomyopathy. Front. Immunol., v. 9, p. 1-16, Apr. 2018. 1664-3224 10.3389/fimmu.2018.00615 |
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eng |
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Frontiers Media |
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