Doxycycline and Benznidazole Reduce the Profile of Th1, Th2, and Th17 Chemokines and Chemokine Receptors in Cardiac Tissue from ChronicTrypanosoma cruzi-Infected Dogs.
Chemokines (CKs) and chemokine receptors (CKR) promote leukocyte recruitment into cardiac tissue infected by theTrypanosoma cruzi. This 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. Thirty mongrel dogs were infected, or not, with the Berenice-78 strain ofT. cruziand grouped according their treatments: (i) two months after infection, Dox (50 mg/kg) 2x/day for 12 months; (ii) nine months after infection, Bz (3,5 mg/kg) 2x/day for 60 days; (iii) Dox + Bz; and (iv) vehicle. After 14 months of infection, hearts were excised and processed for qPCR analysis of Th1 (CCL2, CCL3, CCL4, CCL5, CXCL9, and CXCL11), Th2 (CCL1, CCL17, CCL24, and CCL26), Th17 (CCL20) CKs, Th1 (CCR5, CCR6, and CXCR3), and Th2/Th17 (CCR3, CCR4, and CCR8) CKR, as well as IL-17.T. cruziinfection 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 effect of Dox with Bz, during the chronic phase of infection suggesting a promising therapy for cardiac protection.
Programa de Pós-Graduação em Ciências Biológicas/NUPEB, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brazil.
Guilherme
G
de Paula Costa
Programa de Pós-Graduação em Ciências Biológicas/NUPEB, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brazil.
Laís Roquete
LR
Lopes
Faculdade de Medicina de Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil.
Maria Cláudia
0000-0002-7205-2147
MC
da Silva
Programa de Pós-Graduação em Ciências Biológicas/NUPEB, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brazil.
Aline Luciano
AL
Horta
Programa de Pós-Graduação em Ciências Biológicas/NUPEB, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brazil.
Washington Martins
WM
Pontes
Faculdade de Medicina de Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil.
Cristiane M
CM
Milanezi
Universidade Federal do Rio Grande do Norte Federal, Natal, RN, Brazil.
Paulo Marcos da Mata
PM
Guedes
Programa de Pós-Graduação em Ciências Biológicas/NUPEB, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brazil; Departamento de Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brazil.
Wanderson Geraldo
WG
de Lima
Departments of Pediatrics & Pharmacology, Cardiovascular Research Centre, University of Alberta, Edmonton, AB, Canada.
Richard
R
Schulz
Faculdade de Medicina de Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil.
João Santana
0000-0002-3410-3927
JS
da Silva
Programa de Pós-Graduação em Ciências Biológicas/NUPEB, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brazil; Departamento de Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brazil; Programa de Pós-Graduação em Saúde e Nutrição, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brazil.
Andre
0000-0002-6685-6229
A
Talvani
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