Research Article Doxycycline and Benznidazole Reduce the Profile of Th1, Th2, and Th17 Chemokines and Chemokine Receptors in Cardiac Tissue from Chronic Trypanosoma cruzi-Infected Dogs Guilherme de Paula Costa, 1 Laís Roquete Lopes, 1 Maria Cláudia da Silva, 2 Aline Luciano Horta, 1 Washington Martins Pontes, 1 Cristiane M. Milanezi, 2 Paulo Marcos da Mata Guedes, 3 Wanderson Geraldo de Lima, 1,4 Richard Schulz, 5 João Santana da Silva, 2 and Andre Talvani 1,4,6 1 Programa de P´ os-Graduac ¸˜ ao em Ciˆ encias Biol´ ogicas/NUPEB, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brazil 2 Faculdade de Medicina de Ribeir˜ ao Preto, USP, Ribeir˜ ao Preto, SP, Brazil 3 Universidade Federal do Rio Grande do Norte Federal, Natal, RN, Brazil 4 Departamento de Ciˆ encias Biol´ ogicas, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brazil 5 Departments of Pediatrics & Pharmacology, Cardiovascular Research Centre, University of Alberta, Edmonton, AB, Canada 6 Programa de P´ os-Graduac ¸˜ ao em Sa´ ude e Nutric ¸˜ ao, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brazil Correspondence should be addressed to Andre Talvani; talvani@nupeb.ufop.br Received 2 April 2016; Revised 14 July 2016; Accepted 4 August 2016 Academic Editor: Sandra Helena Penha Oliveira Copyright © 2016 Guilherme de Paula Costa et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Chemokines (CKs) and chemokine receptors (CKR) promote leukocyte recruitment into cardiac tissue infected by the Trypanosoma cruzi. Tis study investigated the long-term treatment with subantimicrobial doses of doxycycline (Dox) in association, or not, with benznidazole (Bz) on the expression of CK and CKR in cardiac tissue. Tirty mongrel dogs were infected, or not, with the Berenice- 78 strain of T. cruzi and grouped according their treatments: (i) two months afer infection, Dox (50 mg/kg) 2x/day for 12 months; (ii) nine months afer infection, Bz (3,5mg/Kg) 2x/day for 60 days; (iii) Dox + Bz; and (iv) vehicle. Afer 14 months of infection, hearts were excised and processed for qPCR analysis of T1 (CCL2, CCL3, CCL4, CCL5, CXCL9, and CXCL11), T2 (CCL1, CCL17, CCL24, and CCL26), T17 (CCL20) CKs, T1 (CCR5, CCR6, and CXCR3), and T2/T17 (CCR3, CCR4, and CCR8) CKR, as well as IL-17. T. cruzi infection increases CCL1, CCL2, CCL4, CCL5, CCL17, CXCL10, and CCR5 expression in the heart. Dox, Bz, or Dox + Bz treatments cause a reversal of CK and CKR and reduce the expression of CCL20, IL-17, CCR6, and CXCR3. Our data reveal an immune modulatory efect of Dox with Bz, during the chronic phase of infection suggesting a promising therapy for cardiac protection. 1. Introduction Chemokines are low molecular weight proteins that promote leukocyte trafcking in homeostasis and infammatory pro- cesses. Chronic infammation is usually characterized by the persistence of leukocyte infltration into the infammatory site driven by chemokine production [1–3]. In particular, Trypanosoma cruzi infection is a well-known parasite disease where the presence of this protozoan triggers activation and continued leukocyte infltration into the muscle tissues in order to eliminate it [4–6]. Since the stimulus persists over months, years, or decades, cell infltration conducted by T1 and T2-like chemokines and their receptors may lead to loss of tissue’s architecture and function, in some cases causing severe disability, especially in the heart [7, 8]. Afer the interaction between T. cruzi and mammalian host cells, the activation of innate resident macrophages/ neutrophils combined with the mobilization of natural killer Hindawi Publishing Corporation Mediators of Inflammation Volume 2016, Article ID 3694714, 11 pages http://dx.doi.org/10.1155/2016/3694714