Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/10177
Title: Tumor Necrosis Factor Is a Therapeutic Target for Immunological Unbalance and Cardiac Abnormalities in Chronic Experimental Chagas’ Heart Disease
Authors: Pereira, Isabela Resende
Pereira, Glaucia Vilar
Silva, Andrea Alice
Moreira, Otacílio Cruz
Britto, Constança
Sarmento, Ellen Diana Marinho
Vietra, Joseli Lannes
Affilliation: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.
Universidade Federal Fluminense. Departamento de Patologia. Niterói, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.
Abstract: Background. Chagas disease (CD) is characterized by parasite persistence and immunological unbalance favoring systemic inflammatory profile. Chronic chagasic cardiomyopathy, the main manifestation of CD, occurs in a TNF-enriched milieu and frequently progresses to heart failure. Aimof the Study. To challenge the hypothesis that TNF plays a key role in Trypanosoma cruziinduced immune deregulation and cardiac abnormalities, we tested the effect of the anti-TNF antibody Infliximab in chronically T. cruzi-infected C57BL/6 mice, a model with immunological, electrical, and histopathological abnormalities resembling Chagas’ heart disease. Results. Infliximab therapy did not reactivate parasite but reshaped the immune response as reduced TNF mRNA expression in the cardiac tissue and plasma TNF and IFN𝛾 levels; diminished the frequency of IL-17A+ but increased IL-10+ CD4+ T-cells; reduced TNF+ but augmented IL-10+ Ly6C+ and F4/80+ cells. Further, anti-TNF therapy decreased cytotoxic activity but preserved IFN𝛾-producing VNHRFTLV-specific CD8+ T-cells in spleen and reduced the number of perforin+ cells infiltrating the myocardium. Importantly, Infliximab reduced the frequency of mice afflicted by arrhythmias and second degree atrioventricular blocks and decreased fibronectin deposition in the cardiac tissue. Conclusions. Our data support that TNF is a crucial player in the pathogenesis of Chagas’ heart disease fueling immunological unbalance which contributes to cardiac abnormalities.
Keywords: Trypanosoma cruzi
Chagas Disease
Chagas Cardiomyopathy
keywords: Doença de Chagas
Trypanosma cruzi
Cardiomiopatia Chagásica
DeCS: Cardiomiopatia Chagásica
Issue Date: 2014
Publisher: Hindawi Publishing Corporation
Citation: PEREIRA, Isabela Rezende et al. Tumor Necrosis Factor Is a Therapeutic Target for Immunological Unbalance and Cardiac Abnormalities in Chronic Experimental Chagas’ Heart Disease. Mediators of Inflammation, v.2014, Article ID 798078, 16p, 2014.
DOI: 10.1155/2014/798078
Copyright: open access
Appears in Collections:IOC - Artigos de Periódicos

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