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- Title
Immunoregulatory mechanisms in Chagas disease: modulation of apoptosis in T-cell mediated immune responses.
- Authors
Chaves, Ana Thereza; Silva Gomes Estanislau, Juliana de Assis; Araújo Fiuza, Jacqueline; Teixeira Carvalho, Andréa; Ferreira, Karine Silvestre; Gomes Fares, Rafaelle Christine; Gazzinelli Guimarães, Pedro Henrique; de Souza Fagundes, Elaine Maria; Morato, Maria José; Fujiwara, Ricardo Toshio; Otávio da Costa Rocha, Manoel; Correa-Oliveira, Rodrigo; de Assis Silva Gomes Estanislau, Juliana; Fiuza, Jacqueline Araújo; Carvalho, Andréa Teixeira; Fares, Rafaelle Christine Gomes; Guimarães, Pedro Henrique Gazzinelli; da Costa Rocha, Manoel Otávio
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
CHAGAS' disease immunology; APOPTOSIS; IMMUNOREGULATION; CASPASE genetics; T cells; TRYPANOSOMA cruzi; THERAPEUTICS; ANTIGENS; CELL physiology; COMPARATIVE studies; CYTOKINES; FLOW cytometry; RESEARCH methodology; MEDICAL cooperation; CARDIOMYOPATHIES; PROTOZOA; RESEARCH; TRYPANOSOMIASIS; TUMOR necrosis factors; EVALUATION research; DISEASE complications
- Publication
BMC Infectious Diseases, 2016, Vol 16, p1
- ISSN
1471-2334
- Publication type
journal article
- DOI
10.1186/s12879-016-1523-1