| Author | Batista, Angelica Martins | |
| Author | Alvarado Arnez, Lucia Elena | |
| Author | Alves, Silvia Marinho Martins | |
| Author | Melo, Gloria | |
| Author | Pereira, Isabela Resende | |
| Author | Ruivo, Leonardo Alexandre de Souza | |
| Author | Silva, Andréa Alice da | |
| Author | Gibaldi, Daniel | |
| Author | Silva, Thayse do Espirito Santo Protasio da | |
| Author | Lorena, Virginia Maria Barros de | |
| Author | Melo, Adriene Siqueira de | |
| Author | Soares, Ana Karine de Araújo | |
| Author | Barros, Michelle da Silva | |
| Author | Costa, Vláudia Maria Assis | |
| Author | Cardoso, Cynthia Chester | |
| Author | Pacheco, Antonio Guilherme Fonseca | |
| Author | Carrazzone, Cristina de Fátima Velloso | |
| Author | Oliveira Jr., Wilson | |
| Author | Moraes, Milton Ozório | |
| Author | Lannes-Vieira, Joseli | |
| Access date | 2018-04-12T11:27:35Z | |
| Available date | 2018-04-12T11:27:35Z | |
| Document date | 2018 | |
| Citation | 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. Frontiers in Immunology, v. 9, p. 1-16, 10 Apr. 2018. | |
| ISSN | 1664-3224 | |
| URI | https://www.arca.fiocruz.br/handle/icict/25789 | |
| Description | Produção científica do Laboratório de Biologia das Interações. | pt_BR |
| Description | Produção científica do Laboratório de Hanseníase. | pt_BR |
| Sponsorship | This work was supported by grants from Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/FAPERJ (CNE/E-26/101.549/2010; E-26/110.153/2013; E-26/111.709/2013) and the Brazilian Research Council/CNPq (474234/2012-6-Universal; 474926/2012-5- Universal, 474234/2012-6; INCTV, National Institute for Science and Technology for Vaccines; DECIT/MS/CNPq 403979/2012-9; BPP 429607-3664961416; PROEP/IOC/CNPq 400146/2011). | |
| Sponsorship | Joseli Lannes-Vieira and Milton Ozório Moraes are research fellows of the Brazilian Research Council/CNPq and CNE/Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/FAPERJ. | |
| Sponsorship | Angelica Martins Batista was supported as a postdoctoral fellow by the funding agency Conselho Nacional de Desenvolvimento Científico e Tecnológico/CNPq and was a CL/IOC fellow. | |
| Sponsorship | Lucia Elena Alvarado Arnez was supported as a postdoctoral fellow by PPSUS and PAPD programs funded by CAPES and FAPERJ. | |
| Language | eng | en_US |
| Publisher | Frontiers Media | |
| Related document | https://www.arca.fiocruz.br/handle/icict/23621 | |
| Rights | open access | |
| Title | Genetic polymorphism at CCL5 is associated with protection in Chagas' heart disease: antagonistic participation of CCR1⁺ and CCR5⁺ cells in chronic chagasic cardiomyopathy | en_US |
| Type | Article | |
| DOI | 10.3389/fimmu.2018.00615 | |
| Abstract | 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 Ccr5ˉ/ˉ 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. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | 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. | |
| Affilliation | Pronto Socorro Cardiológico de Pernambuco. Ambulatório de Doença de Chagas e Insuficiência Cardíaca. Recife, PE, Brasil. | |
| Affilliation | Pronto Socorro Cardiológico de Pernambuco. Ambulatório de Doença de Chagas e Insuficiência Cardíaca. Recife, PE, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Universidade Federal Fluminense. Faculdade de Medicina. Departamento de Patologia. Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas. Niterói, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de Imunologia. Laboratório de Imunoparasitologia. Recife, PE, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de Imunologia. Laboratório de Imunoparasitologia. Recife, PE, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de Imunologia. Laboratório de Imunoparasitologia. Recife, PE, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de Imunologia. Laboratório de Imunoparasitologia. Recife, PE, Brasil. | |
| Affilliation | Universidade Federal de Pernambuco. Departamento de Medicina Tropical. Recife, PE, Brasil / Universidade Federal de Pernambuco. Laboratório de Imunopatologia Keizo Asami. Recife, PE, Brasil. | |
| Affilliation | Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Biologia. Departamento de Genética. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Presidência. Programa de Computação Científica. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Pronto Socorro Cardiológico de Pernambuco. Ambulatório de Doença de Chagas e Insuficiência Cardíaca. Recife, PE, Brasil. | |
| Affilliation | Pronto Socorro Cardiológico de Pernambuco. Ambulatório de Doença de Chagas e Insuficiência Cardíaca. Recife, PE, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil. | |
| Subject | Chagas disease | en_US |
| Subject | Trypanosoma cruzi | en_US |
| Subject | Heart disease | en_US |
| Subject | Cell migration | en_US |
| Subject | CCL5 | en_US |
| Subject | CCR1 | en_US |
| Subject | CCR5 | en_US |
| Subject | Met-RANTES | en_US |
| e-ISSN | 1664-3224 | |
