Caspase inhibition reduces lymphocyte apoptosis and improves host immune responses to Trypanosoma cruzi infection

dc.creatorSilva, Elisabeth Martins da
dc.creatorGuillermo, Landi Veivi Costilla
dc.creatorGomes, Flávia Lima Ribeiro
dc.creatorMeis, Juliana De
dc.creatorNunes, Marise Pinheiro
dc.creatorSenra, Juliana Fraga Vasconcelos
dc.creatorSoares, Milena Botelho Pereira
dc.creatorReis, George Alexandre dos
dc.creatorLopes, Marcela de Freitas
dc.date2015-04-22T18:34:19Z
dc.date2015-04-22T18:34:19Z
dc.date2007
dc.date.accessioned2023-09-26T20:16:17Z
dc.date.available2023-09-26T20:16:17Z
dc.identifierSILVA, 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.
dc.identifier0014-2980
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/10113
dc.identifier10.1002/eji.200636790
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8852981
dc.descriptionIn 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherWiley-VCH Verlag GmbH & Co
dc.rightsopen access
dc.subjectApoptosis
dc.subjectCaspases
dc.subjectInfection
dc.subjectLymphocyte
dc.subjectTrypanosoma cruzi
dc.subjectApoptose/imunologia
dc.subjectInibidores de Caspase
dc.subjectDoença de Chagas/imunologia
dc.subjectDoença de Chagas/patologia
dc.subjectLinfócitos/enzimologia
dc.subjectTrypanosoma cruzi/imunologia
dc.subjectClorometilcetonas de Aminoácidos/farmacologia
dc.subjectAnimais
dc.subjectApoptose/efeitos de drogas
dc.subjectDoença de Chagas/quimioterapia
dc.subjectLinfócitos/efeitos de drogas
dc.subjectMasculino
dc.subjectCamundongos
dc.subjectCamundongos Endogâmicos BALB C
dc.titleCaspase inhibition reduces lymphocyte apoptosis and improves host immune responses to Trypanosoma cruzi infection
dc.typeArticle


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