Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/10113
Title: Caspase inhibition reduces lymphocyte apoptosis and improves host immune responses to Trypanosoma cruzi infection
Authors: Silva, Elisabeth Martins da
Guillermo, Landi Veivi Costilla
Gomes, Flávia Lima Ribeiro
Meis, Juliana De
Nunes, Marise Pinheiro
Senra, Juliana Fraga Vasconcelos
Soares, Milena Botelho Pereira
Reis, George Alexandre dos
Lopes, Marcela de Freitas
Affilliation: Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.
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.
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.
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.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.
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.
Keywords: Apoptosis
Caspases
Infection
Lymphocyte
Trypanosoma cruzi
DeCS: Apoptose/imunologia
Inibidores de Caspase
Doença de Chagas/imunologia
Doença de Chagas/patologia
Linfócitos/enzimologia
Trypanosoma cruzi/imunologia
Clorometilcetonas de Aminoácidos/farmacologia
Animais
Apoptose/efeitos de drogas
Doença de Chagas/quimioterapia
Linfócitos/efeitos de drogas
Masculino
Camundongos
Camundongos Endogâmicos BALB C
Issue Date: 2007
Publisher: Wiley-VCH Verlag GmbH & Co
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.
DOI: 10.1002/eji.200636790
ISSN: 0014-2980
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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