Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/8571
Title: Administration of granulocyte colony-stimulating factor induces immunomodulation, recruitment of T regulatory cells, reduction of myocarditis and decrease of parasite load in a mouse model of chronic Chagas disease cardiomyopathy.
Authors: Vasconcelos, Juliana Fraga
Souza, Bruno Solano de Freitas
Lins, Thayse Fernanda da Silva
Garcia, Letícia Maria da Silva
Kaneto, Carla Martins
Sampaio, Geraldo Pedral
Alcantara, Adriano Costa de
Meira, Cássio Santana
Macambira, Simone Garcia
Santos, Ricardo Ribeiro dos
Soares, Milena Botelho Pereira
Affilliation: Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Universidade Estadual de Santa Cruz. Ilhéus, BA, Brasil
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil
ospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil
Abstract: 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 µg/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-γ and tumor necrosis factor-α and increased interleukin-10 and transforming growth factor-ß 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 (Treg) 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 Treg cells in the immunosuppression induced by G-CSF treatment and reinforces its potential therapeutic use for patients with Chagas disease
Keywords: Trypanosoma cruzi
Cytokine therapy
Inflammation
Fibrosis
Th1 modulation
DeCS: Cardiomiopatia Chagásica/quimioterapia
Fator Estimulador de Colônias de Granulócitos/uso terapêutico
Imunomodulação
Miocardite/quimioterapia
Linfócitos T Reguladores/efeitos de drogas
Animais
Antígenos CD3/genética
Cardiomiopatia Chagásica/imunologia
Citocinas/genética
Fibrose/quimioterapia
Fatores de Transcrição Forkhead/genética
Galectina 3/genética
Fator Estimulador de Colônias de Granulócitos/administração & dosagem
Humanos
Injeções Intraperitoneais
Molécula 1 de Adesão Intercelular/genética
Camundongos Endogâmicos C57BL
Miocárdio/imunologia
Sindecana-4/genética
Transcrição Genética
Trypanosoma cruzi/efeitos de drogas
Issue Date: 2013
Publisher: Federation of American Society of Experimental Biology
Citation: VASCONCELOS, J. F. et al. Administration of granulocyte colony-stimulating factor induces immunomodulation, recruitment of T regulatory cells, reduction of myocarditis and decrease of parasite load in a mouse model of chronic Chagas disease cardiomyopathy. FASEB Journal, v. 27, n. 12, p. 4691-4702, 2013.
DOI: 10.1096/fj.13-229351
ISSN: 1530-6860
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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