Please use this identifier to cite or link to this item: http://www.arca.fiocruz.br/handle/icict/20113
Title: Immunoregulatory mechanisms in Chagas disease: modulation of apoptosis in T-cell mediated immune responses
Authors: Chaves, Ana Thereza
Estanislau, Juliana de Assis Silva Gomes
Fiuza, Jacqueline Araújo
Carvalho, Andréa Teixeira
Ferreira, Karine Silvestre
Fares, Rafaelle Christine Gomes
Guimarães, Pedro Henrique Gazzinelli
Fagundes, Elaine Maria de Souza
Morato, Maria José
Fujiwara, Ricardo Toshio
Rocha, Manoel Otávio da Costa
Oliveira, Rodrigo Correa de
Affilliation: Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunologia Celular e Molecular. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunologia Celular e Molecular. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Laboratório de Biologia das Interações Celulares. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Faculdade de Medicina Programa de Pós graduação em Medicina Tropical e Infectologia. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunologia Celular e Molecular. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Biomarcadores de Diagnóstico e Monitoração. Belo Horizonte, MG, Brazil.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Laboratório de Biologia das Interações Celulares. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunologia Celular e Molecular. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Parasitologia. Laboratório de Imunologia e Genômica de Parasitos. Belo Horizonte, MG, Brazil.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Fisiologia e Biofísica. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunologia Celular e Molecular. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Parasitologia. Laboratório de Imunologia e Genômica de Parasitos. Belo Horizonte, MG, Brazil.
Universidade Federal de Minas Gerais. Faculdade de Medicina Programa de Pós graduação em Medicina Tropical e Infectologia. Belo Horizonte, MG, Brazil.
Laboratório de Imunologia Celular e Molecular, Centro de Pesquisas René Rachou, Fiocruz, Belo Horizonte, Brazil/Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais. Belo Horizonte, MG, Brazil/Universidade Federal de Ouro Preto. Ouro Preto, MG, Brazil.
Abstract: BACKGROUND: Chronic Chagas disease presents different clinical manifestations ranging from asymptomatic (namely indeterminate) to severe cardiac and/or digestive. Previous results have shown that the immune response plays an important role, although no all mechanisms are understood. Immunoregulatory mechanisms such as apoptosis are important for the control of Chagas disease, possibly affecting the morbidity in chronic clinical forms. Apoptosis has been suggested to be an important mechanism of cellular response during T. cruzi infection. We aimed to further understand the putative role of apoptosis in Chagas disease and its relation to the clinical forms of the disease. METHODS: Apoptosis of lymphocytes, under antigenic stimuli (soluble T. cruzi antigens - TcAg) where compared to that of non-stimulated cells. Apoptosis was evaluated using the expression of annexin and caspase 3(+) by T cells and the percentage of cells positive evaluated by flow cytometry. In addition activation and T cell markers were used for the identification of TCD4(+) and TCD8(+) subpopulations. The presence of intracellular and plasma cytokines were also evaluated. Analysis of the activation status of the peripheral blood cells showed that patients with Chagas disease presented higher levels of activation determined by the expression of activation markers, after TcAg stimulation. PCR array were used to evaluate the contribution of this mechanism in specific cell populations from patients with different clinical forms of human Chagas disease. RESULTS: Our results showed a reduced proliferative response associated a high expression of T CD4(+)CD62L(-) cells in CARD patients when compared with IND group and NI individuals. We also observed that both groups of patients presented a significant increase of CD4(+) and CD8(+) T cell subsets in undergoing apoptosis after in vitro stimulation with T. cruzi antigens. In CARD patients, both CD4(+) and CD8(+) T cells expressing TNF-α were highly susceptible to undergo apoptosis after in vitro stimulation. Interestingly, the in vitro TcAg stimulation increased considerably the expression of cell death TNF/TNFR superfamily and Caspase family receptors genes in CARD patients. CONCLUSIONS: Taken together, our results suggest that apoptosis may be an important mechanism for the control of morbidity in T. cruzi infection by modulating the expression of apoptosis genes, the cytokine environment and/or killing of effector cells.
Keywords: Apoptosis
Caspase family
Chagas disease
Immunoregulation
T lymphocytes
TNF/TNFR superfamily
keywords: Doença de chagas
Trypanosoma cruzi
Issue Date: 2016
Publisher: BioMed Central
Citation: CHAVES, Ana Thereza et al. Immunoregulatory mechanisms in Chagas disease: modulation of apoptosis in T-cell mediated immune responses. BMC Infect Dis., v. 16, p. 191.
DOI: 10.1186/s12879-016-1523-1
ISSN: 1471-2334
Copyright: open access
Appears in Collections:IRR - Artigos de Periódicos

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