Immunoregulatory mechanisms in Chagas disease: modulation of apoptosis in T-cell mediated immune responses
| Autor: | Pedro Henrique Gazzinelli Guimarães, Maria José F. Morato, Ana Thereza Chaves, Ricardo Toshio Fujiwara, Karine Silvestre Ferreira, Rafaelle Christine Gomes Fares, Andréa Teixeira de Carvalho, Jacqueline Araújo Fiuza, Juliana de Assis Silva Gomes Estanislau, Rodrigo Correa-Oliveira, Manoel Otávio da Costa Rocha, Elaine Maria de Souza Fagundes |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine Chagas disease Programmed cell death Trypanosoma cruzi medicine.medical_treatment T cell T lymphocytes Antigens Protozoan Apoptosis CD8-Positive T-Lymphocytes Biology 03 medical and health sciences 0302 clinical medicine Immune system Antigen T-Lymphocyte Subsets medicine Humans L-Selectin TNF/TNFR superfamily Aged Cell Proliferation Tumor Necrosis Factor-alpha Immunoregulation Middle Aged Flow Cytometry 030104 developmental biology Infectious Diseases Cytokine medicine.anatomical_structure Caspase family Immunology Cytokines Female Tumor necrosis factor alpha Cardiomyopathies CD8 Research Article 030215 immunology |
| Zdroj: | BMC Infectious Diseases |
| ISSN: | 1471-2334 |
| DOI: | 10.1186/s12879-016-1523-1 |
| Popis: | 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. Electronic supplementary material The online version of this article (doi:10.1186/s12879-016-1523-1) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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