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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
Author(s) -
Vasconcelos Juliana F.,
Souza Bruno S. F.,
Lins Thayse F. S.,
Garcia Letícia M. S.,
Kaneto Carla M.,
Sampaio Geraldo P.,
Alcântara Adriano C.,
Meira Cássio S.,
Macambira Simone G.,
RibeirodosSantos Ricardo,
Soares Milena B. P.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.13-229351
Subject(s) - trypanosoma cruzi , immunology , granulocyte colony stimulating factor , chagas disease , tumor necrosis factor alpha , inflammation , myocarditis , immune system , cytokine , medicine , fibrosis , immunosuppression , foxp3 , biology , parasite hosting , chemotherapy , world wide web , computer science
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‐β 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.—Vasconcelos, J. F., Souza, B. S. F., Lins, T. F. S., Garcia, L. M. S., Kaneto, C. M., Smapaio, G. P., de Alcântara, A. C., Meira, C. S., Macambira, S. G., Ribeiro‐dos‐Santos, R., Soares, M. B. P., 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 J. 27, 4691–4702 (2013). www.fasebj.org