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Treatment with a pan\u2010caspase blocker peptide inhibited expression of the active form of effector caspase\u20103 <jats:italic>in vitro<\/jats:italic> and rescued both B and T cells from cell death. Injection of the caspase inhibitor benzyloxycarbonyl\u2010Val\u2010Ala\u2010Asp(OMe)\u2010fluoromethyl ketone, but not a control peptide, reduced parasitemia and lymphocyte apoptosis in <jats:italic>T.\u2004cruzi<\/jats:italic>\u2010infected 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\u2010\u03b3 by splenocytes stimulated with <jats:italic>T.\u2004cruzi<\/jats:italic> antigens. Caspase inhibition in the course of infection reduced the intracellular load of parasites in peritoneal macrophages, and increased the production of TNF\u2010\u03b1 and nitric oxide upon activation <jats:italic>in vitro<\/jats:italic>. Our results indicate that inhibition of caspases with a pan\u2010caspase blocker peptide improves protective type\u20101 immune responses to <jats:italic>T.\u2004cruzi<\/jats:italic> infection. We suggest that mechanisms of apoptosis are potential therapeutic targets in Chagas\u2019 disease.<\/jats:p>","DOI":"10.1002\/eji.200636790","type":"journal-article","created":{"date-parts":[[2007,2,13]],"date-time":"2007-02-13T11:44:48Z","timestamp":1171367088000},"page":"738-746","source":"Crossref","is-referenced-by-count":29,"title":["Caspase inhibition reduces lymphocyte apoptosis and improves host immune responses to <i>Trypanosoma cruzi<\/i> infection"],"prefix":"10.1002","volume":"37","author":[{"given":"Elisabeth\u2004M.","family":"Silva","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Landi\u2004V.\u2004C.","family":"Guillermo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fl\u00e1via\u2004L.","family":"Ribeiro\u2010Gomes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliana","family":"De\u2004Meis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marise\u2004P.","family":"Nunes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliana\u2004F.\u2004V.","family":"Senra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milena\u2004B.\u2004P.","family":"Soares","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George\u2004A.","family":"DosReis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcela\u2004F.","family":"Lopes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2007,2,23]]},"reference":[{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3024.1998.00154.x"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/356338a0"},{"key":"e_1_2_7_3_2","doi-asserted-by":"crossref","first-page":"5129","DOI":"10.1128\/iai.61.12.5129-5133.1993","article-title":"Differential susceptibilities of mice genomically deleted of CD4 and CD8 to infections with Trypanosoma cruzi or Trypanosoma brucei.","volume":"61","author":"Rottenberg M. 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