Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/7316
Title: Lutzomyia longipalpis saliva drives apoptosis and enhances parasite burden in neutrophils
Authors: Prates, Deboraci Brito
Santos, Théo de Araújo
Luz, Nívea Farias
Andrade, Bruno de Bezerril
Costa, Jaqueline França
Macêdo, Lilian Maria Afonso de
Clarêncio, Jorge
Miranda, José Carlos
Bozza, Patrícia Torres
Reis, George A. dos
Brodskyn, Claudia Ida
Barral Netto, Manoel
Borges, Valeria de Matos
Barral, Aldina Maria Prado
Affilliation: Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil
National Institute of Allergy and Infectious Diseases. National Institutes of Health. Laboratory of Parasitic Diseases. Besthesda, MD, USA
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia de Investigação em Imunologia (iii-INCT). Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia de Investigação em Imunologia (iii-INCT). Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia de Investigação em Imunologia (iii-INCT). Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia de Investigação em Imunologia (iii-INCT). Salvador, BA, Brasil
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 PGE(2) 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.
DeCS: Apoptose
Leishmaniose/imunologia
Neutrófilos/patologia
Neutrófilos/parasitologia
Psychodidae/imunologia
Saliva/imunologia
Animais
Caspases/metabolismo
Quimiotaxia
Quimiocina CCL2/metabolismo
Feminino
Proteína Ligante Fas/metabolismo
Interações Hospedeiro-Parasita
Immunoblotting
Leishmania
Leishmaniose/parasitologia
Macrófagos/imunologia
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Neutrófilos/imunologia
Psychodidae/parasitologia
Espécies de Oxigênio Reativas/metabolismo
Saliva/química
Saliva/parasitologia
Glândulas Salivares/citologia
Glândulas Salivares/imunologia
Glândulas Salivares/parasitologia
Issue Date: 2011
Publisher: Society for Leukocyte Biology
Citation: PRATES, D. B. et al. Lutzomyia longipalpis saliva drives apoptosis and enhances parasite burden in neutrophils. Journal of Leukocyte Biology, v. 90, n. 3, p.575-582, 2011.
DOI: 10.1189/jlb.0211105
ISSN: 1938-3673
Copyright: open access
Appears in Collections:IGM - Artigos de Periódicos

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