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metadata.dc.type: | Artigo de Periódico |
Title: | Lutzomyia longipalpis saliva drives apoptosis and enhances parasite burden in neutrophils |
Other Titles: | Journal of Leukocyte Biology |
Authors: | Santos, Théo Araújo Luz, Nívea Farias Andrade, Bruno Bezerril Costa, Jaqueline França Afonso, Lilian Clarêncio, Jorge Miranda, José Carlos Bozza, Patrícia Torres Reis, George A. dos Brodskyn, Claudia Ida Barral-Netto, Manoel Borges, Valéria de Matos Barral, Aldina Maria Prado |
metadata.dc.creator: | Santos, Théo Araújo Luz, Nívea Farias Andrade, Bruno Bezerril Costa, Jaqueline França Afonso, Lilian Clarêncio, Jorge Miranda, José Carlos Bozza, Patrícia Torres Reis, George A. dos Brodskyn, Claudia Ida Barral-Netto, Manoel Borges, Valéria de Matos Barral, Aldina Maria Prado |
Abstract: | Neutrophils are considered the host's first line of defense against infections and have been implicated in the immunopathogenesis of Leishmaniasis. Leishmania parasites are inoculated alongside vectors' saliva, which is a rich source of pharmacologically active substances that interfere with host immune response. In the present study, we tested the hypothesis that salivary components from Lutzomyia longipalpis, an important vector of visceral Leishmaniasis, enhance neutrophil apoptosis. Murine inflammatory peritoneal neutrophils cultured in the presence of SGS presented increased surface expression of FasL and underwent caspase-dependent and FasL-mediated apoptosis. This proapoptosis effect of SGS on neutrophils was abrogated by pretreatment with protease as well as preincubation with antisaliva antibodies. Furthermore, in the presence of Leishmania chagasi, SGS also increased apoptosis on neutrophils and increased PGE2 release and decreased ROS production by neutrophils, while enhancing parasite viability inside these cells. The increased parasite burden was abrogated by treatment with z-VAD, a pan caspase inhibitor, and NS-398, a COX-2 inhibitor. In the presence of SGS, Leishmania-infected neutrophils produced higher levels of MCP-1 and attracted a high number of macrophages by chemotaxis in vitro assays. Both of these events were abrogated by pretreatment of neutrophils with bindarit, an inhibitor of CCL2/MCP-1 expression. Taken together, our data support the hypothesis that vector salivary proteins trigger caspase-dependent and FasL-mediated apoptosis, thereby favoring Leishmania survival inside neutrophils, which may represent an important mechanism for the establishment of Leishmania infection. |
Keywords: | Leishmania chagasi Sand fly Cell death FasL Chemotaxis |
metadata.dc.rights: | Acesso Aberto |
URI: | http://repositorio.ufba.br/ri/handle/ri/17866 |
Issue Date: | 2011 |
Appears in Collections: | Artigo Publicado em Periódico (Faculdade de Medicina) |
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