April 2018 | Volume 9 | Article 615 1 ORIGINAL RESEARCH published: 11 April 2018 doi: 10.3389/fmmu.2018.00615 Frontiers in Immunology | www.frontiersin.org Edited by: Celio Geraldo Freire-de-Lima, Universidade Federal do Rio de Janeiro, Brazil Reviewed by: Catherine Ropert, Universidade Federal de Minas Gerais, Brazil Elisangela Oliveira De Freitas, University of São Paulo, Brazil Phileno Pinge-Filho, Universidade Estadual de Londrina, Brazil *Correspondence: Joseli Lannes-Vieira lannes@ioc.focruz.br † Present address: Lucia Elena Alvarado-Arnez, Coordinación de Investigación, Universidad Franz Tamayo/ UNIFRANZ, Cochabamba, Bolivia; Isabela Resende Pereira, Laboratório de Hematologia, Departamento de Patologia, Faculdade de Medicina, Universidade Federal Fluminense, Niterói, Rio de Janeiro, Brazil; Adriene Siqueira de Melo, Faculdade Pernambucana de Saúde, Recife, Pernambuco, Brazil ‡ These authors have contributed equally to this work. Specialty section: This article was submitted to Microbial Immunology, a section of the journal Frontiers in Immunology Received: 12 December 2017 Accepted: 12 March 2018 Published: 11 April 2018 Genetic Polymorphism at CCL5 Is Associated With Protection in Chagas’ Heart Disease: Antagonistic Participation of CCR1 + and CCR5 + Cells in Chronic Chagasic Cardiomyopathy Angelica Martins Batista 1‡ , Lucia Elena Alvarado-Arnez 1,2‡ , Silvia Marinho Alves 3 , Gloria Melo 3 , Isabela Resende Pereira 1† , Leonardo Alexandre de Souza Ruivo 1 , Andrea Alice da Silva 4 , Daniel Gibaldi 1 , Thayse do E. S. Protásio da Silva 1 , Virginia Maria Barros de Lorena 5 , Adriene Siqueira de Melo 5† , Ana Karine de Araújo Soares 5 , Michelle da Silva Barros 5 , Vláudia Maria Assis Costa 6,7 , Cynthia C. Cardoso 8 , Antonio G. Pacheco 9 , Cristina Carrazzone 3 , Wilson Oliveira Jr. 3 , Milton Ozório Moraes 2 and Joseli Lannes-Vieira 1 * 1 Laboratório de Biologia das Interações, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil, 2 Laboratório de Hanseníase, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil, 3 Ambulatório de Doença de Chagas e Insufciência Cardíaca do Pronto Socorro Cardiológico de Pernambuco (PROCAPE/UPE), Recife, Brazil, 4 Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas, Departamento de Patologia, Faculdade de Medicina, Universidade Federal Fluminense, Rio de Janeiro, Brazil, 5 Laboratório de Imunoparasitologia, Departamento de Imunologia, Instituto Aggeu Magalhães, Fundação Oswaldo Cruz (Fiocruz), Recife, Brazil, 6 Departamento de Medicina Tropical, Universidade Federal de Pernambuco, Recife, Brazil, 7 Laboratório de Imunopatologia Keizo Asami (LIKA), Universidade Federal de Pernambuco, Recife, Brazil, 8 Laboratório de Virologia Molecular, Departamento de Genética, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil, 9 Programa de Computação Científca, Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil Chronic cardiomyopathy is the main clinical manifestation of Chagas disease (CD), a disease caused by Trypanosoma cruzi infection. A hallmark of chronic chagasic cardio- myopathy (CCC) is a fbrogenic infammation 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 classifed 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