Journal
FASEB JOURNAL
Volume 27, Issue 12, Pages 4691-4702Publisher
WILEY
DOI: 10.1096/fj.13-229351
Keywords
Trypanosoma cruzi; cytokine therapy; inflammation; fibrosis; Th1 modulation
Categories
Funding
- Brazilian Ministry of Sciences and Technology (MCT)
- Conselho Nacional de Pesquisas (CNPq)
- Financiadora de Estudos e Projetos (FINEP)
- Fundacao Oswaldo Cruz (FIOCRUZ)
- Fundacao de Amparo as Pesquisas do Estado da Bahia (FAPESB)
- Coordination for the Improvement of Higher Education Personnel (CAPES) doctoral scholarship from Universidade Estadual de Feira de Santana/Programa de Pos-graduacao em Biotecnologia (UEFS/PPgBIOTEC)
- Rede Nordeste de Biotecnologia (RENORBIO) graduate programs
- CNPq
- FAPESB
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Chagas disease, caused by Trypanosoma cruzi infection, is a leading cause of heart failure in Latin American countries. In a previous study, we showed beneficial effects of granulocyte colony-stimulating factor (G-CSF) administration in the heart function of mice with chronic T. cruzi infection. Presently, we investigated the mechanisms by which this cytokine exerts its beneficial effects. Mice chronically infected with T. cruzi were treated with human recombinant G-CSF (3 courses of 200 mu g/kg/d for 5 d). Inflammation and fibrosis were reduced in the hearts of G-CSF-treated mice, compared with the hearts of vehicle-treated mice, which correlated with decreased syndecan-4, intercellular adhesion molecule-1, and galectin-3 expressions. Marked reductions in interferon-gamma and tumor necrosis factor-alpha and increased interleukin-10 and transforming growth factor-beta were found after G-CSF administration. Because the therapy did not induce a Th1 to Th2 immune response deviation, we investigated the role of regulatory T (T-reg) cells. A significant increase in CD3(+)Foxp3(+) cells was observed in the hearts of G-CSF-treated mice. In addition, a reduction of parasitism was observed after G-CSF treatment. Our results indicate a role of T-reg cells in the immunosuppression induced by G-CSF treatment and reinforces its potential therapeutic use for patients with Chagas disease.
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