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

Autor: Marise P. Nunes, Juliana F. V. Senra, Landi V. C. Guillermo, Juliana de Meis, Flávia L. Ribeiro-Gomes, George A. DosReis, Elisabeth M. Silva, Milena Botelho Pereira Soares, Marcela F. Lopes
Rok vydání: 2007
Předmět:
Zdroj: European Journal of Immunology. 37:738-746
ISSN: 1521-4141
0014-2980
DOI: 10.1002/eji.200636790
Popis: 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.
Databáze: OpenAIRE
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