Author | Silva, Elisabeth Martins da | |
Author | Guillermo, Landi Veivi Costilla | |
Author | Gomes, Flávia Lima Ribeiro | |
Author | Meis, Juliana De | |
Author | Nunes, Marise Pinheiro | |
Author | Senra, Juliana Fraga Vasconcelos | |
Author | Soares, Milena Botelho Pereira | |
Author | Reis, George Alexandre dos | |
Author | Lopes, Marcela de Freitas | |
Access date | 2015-04-22T18:34:19Z | |
Available date | 2015-04-22T18:34:19Z | |
Document date | 2007 | |
Citation | SILVA, E. M. et al. Caspase inhibition reduces lymphocyte apoptosis and improves host immune responses to Trypanosoma cruzi infection. European Joural of Immunology, v. 37, n. 3, p. 738-746, 2007. | pt_BR |
ISSN | 0014-2980 | |
URI | https://www.arca.fiocruz.br/handle/icict/10113 | |
Language | eng | pt_BR |
Publisher | Wiley-VCH Verlag GmbH & Co | pt_BR |
Rights | open access | pt_BR |
Title | Caspase inhibition reduces lymphocyte apoptosis and improves host immune responses to Trypanosoma cruzi infection | pt_BR |
Type | Article | pt_BR |
DOI | 10.1002/eji.200636790 | |
Abstract | In experimental Chagas' disease, lymphocytes from mice infected with Trypanosoma cruzi show increased apoptosis in vivo and in vitro. Treatment with a pan-caspase blocker peptide inhibited expression of the active form of effector caspase-3 in vitro and rescued both B and T cells from cell death. Injection of the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethyl ketone, but not a control peptide, reduced parasitemia and lymphocyte apoptosis in T. cruzi-infected mice. Moreover, treatment with caspase inhibitor throughout acute infection increased the absolute numbers of B and T cells in the spleen and lymph nodes, without affecting cell infiltrates in the heart. Following treatment, we found increased accumulation of memory/activated CD4 and CD8 T cells, and secretion of IFN-gamma by splenocytes stimulated with T. cruzi antigens. Caspase inhibition in the course of infection reduced the intracellular load of parasites in peritoneal macrophages, and increased the production of TNF-alpha and nitric oxide upon activation in vitro. Our results indicate that inhibition of caspases with a pan-caspase blocker peptide improves protective type-1 immune responses to T. cruzi infection. We suggest that mechanisms of apoptosis are potential therapeutic targets in Chagas' disease. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
Subject | Apoptosis | pt_BR |
Subject | Caspases | pt_BR |
Subject | Infection | pt_BR |
Subject | Lymphocyte | pt_BR |
Subject | Trypanosoma cruzi | pt_BR |
DeCS | Apoptose/imunologia | pt_BR |
DeCS | Inibidores de Caspase | pt_BR |
DeCS | Doença de Chagas/imunologia | pt_BR |
DeCS | Doença de Chagas/patologia | pt_BR |
DeCS | Linfócitos/enzimologia | pt_BR |
DeCS | Trypanosoma cruzi/imunologia | pt_BR |
DeCS | Clorometilcetonas de Aminoácidos/farmacologia | pt_BR |
DeCS | Animais | pt_BR |
DeCS | Apoptose/efeitos de drogas | pt_BR |
DeCS | Doença de Chagas/quimioterapia | pt_BR |
DeCS | Linfócitos/efeitos de drogas | pt_BR |
DeCS | Masculino | pt_BR |
DeCS | Camundongos | pt_BR |
DeCS | Camundongos Endogâmicos BALB C | pt_BR |