RIPK1-RIPK3-MLKL-Associated Necroptosis Drives Leishmania infantum Killing in Neutrophils
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2018 |
| Outros Autores: | , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/28935 |
Resumo: | Fundação de Amparo à Pesquisa do Estado da Bahia-FAPESB (JCB0047/2013 to DP, 5760/2015 to VB) and from Conselho Nacional de Desenvolvimento Científico e Tecnológico-CNPq (482722/2013-4 to DP, 552721/2011-5 and 019.203.02712/2009-8 FAPITEC/CNPq to RA). RA also received a grant from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES: 23038. 005304/2011-01). NFL received funding from CAPES (grants 88887.142000/2017-00 and 88887.137958/2017-00). FC is supported by NIH grant AI119030. LAB and LJB received a fellowship from CNPq |
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Barbosa, Laiana ArlegoFiuza, Paloma Peixoto dos SantosBorges, Letícia JRolim, Fellipe AAndrade, Mayara BLuz, Nivea FariasCarvalho, Graziele Quintela deLima, Jonilson BerlinkAlmeida, Roque Pacheco deChan, Francis KBozza, Marcelo TorresBorges, Valeria de MatosPrates, Deboraci Brito2018-09-20T14:02:59Z2018-09-20T14:02:59Z2018BARBOSA, L. A. et al. RIPK1-RIPK3-MLKL-Associated Necroptosis Drives Leishmania infantum Killing in Neutrophils. Frontiers in Immunology, v. 9, 1918.1664-3224https://www.arca.fiocruz.br/handle/icict/2893510.3389/fimmu.2018.01818Fundação de Amparo à Pesquisa do Estado da Bahia-FAPESB (JCB0047/2013 to DP, 5760/2015 to VB) and from Conselho Nacional de Desenvolvimento Científico e Tecnológico-CNPq (482722/2013-4 to DP, 552721/2011-5 and 019.203.02712/2009-8 FAPITEC/CNPq to RA). RA also received a grant from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES: 23038. 005304/2011-01). NFL received funding from CAPES (grants 88887.142000/2017-00 and 88887.137958/2017-00). FC is supported by NIH grant AI119030. LAB and LJB received a fellowship from CNPqUniversidade Federal da Bahia. Salvador, BA, BrasilUniversidade Federal da Bahia. Salvador, BA, BrasilUniversidade Federal da Bahia. Salvador, BA, BrasilUniversidade Federal da Bahia. Salvador, BA, BrasilUniversidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, BrasilUniversidade Federal da Bahia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brasil / Instituto Federal de Educação, Ciência e Tecnologia Baiano. Santa Inês, BA, BrasilUniversidade do Oeste da Bahia. Centro de Ciências Biológicas e da Saúde. Barreiras, BA, BrasilUniversidade Federal de Sergipe. Departamento de Medicina. Aracaju, SE, BrasilUniversity of Massachusetts Medical School. Department of Pathology, Immunology and Microbiology Program. Worcester, MA, United StatesUniversidade Federal do Rio de Janeiro. Departamento de Imunologia. Rio de Janeiro, RJ, BrasilUniversidade Federal da Bahia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brasil / Universidade Federal da Bahia. Instituto de Ciências da Saúde. Departamento de Biomorfologia. Salvador, BA, BrasilNecroptosis is a pro-inflammatory cell death, which happens in the context of caspase-8 inhibition, allowing activation of the receptor interacting protein kinase 1-receptor interacting protein kinase 3-mixed lineage kinase domain-like (RIPK1-RIPK3-MLKL) axis. Recently, necroptosis has emerged as a key component of resistance against pathogens including infected macrophage by Leishmania infantum, the ethiologic agent of Visceral leishmaniasis (VL). VL is the most severe form of Leishmaniasis, characterized by systemic inflammation and neutropenia. However, the role of neutrophil cell death in VL has not been characterized. Here, we showed that VL patients exhibited increased lactate dehydrogenase levels in the serum, a hallmark of cell death and tissue damage. We investigated the effect of necroptosis in neutrophil infection in vitro. Human neutrophils pretreated with zVAD-fmk (pan-caspase inhibitor) and zIETD-fmk (caspase-8 inhibitor) increased reactive oxygen species (ROS) level in response to Leishmania infection, which is associated with necroptotic cell death. MLKL, an important effector molecule downstream of necroptosis pathway, was also required for Leishmania killing. Moreover, in absence of caspases-8, murine neutrophils displayed loss of membrane integrity, higher levels of ROS, and decreased L. infantum viability. Pharmacological inhibition of RIPK1 or RIPK3 increased parasite survival when caspase-8 was blocked. Electron microscopy assays revealed morphological features associated with necroptotic death in L. infantum infected-neutrophils pretreated with caspase inhibitor, whereas infected cells pretreated with RIPK1 and RIPK3 inhibitors did not show ultra-structural alterations in membrane integrity and presented viable Leishmania within parasitophorous vacuoles. Taken together, these findings suggest that inhibition of caspase-8 contributes to elimination of L. infantum in neutrophils by triggering necroptosis. Thus, targeting necroptosis may represent a new strategy to control Leishmania replication.engFrontiers MediaLeishmania infantumNeutrófilosNecroptoseMorte celularRIPK3Linhagem mista parecida com domínio quinaseCaspase-8Leishmania infantumNeutrophilsNecroptosisCell deathRIPK3Mixed lineage kinase domain-likeCaspase-8RIPK1-RIPK3-MLKL-Associated Necroptosis Drives Leishmania infantum Killing in Neutrophilsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/28935/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALBarbosa LA RIPK1-RIPK3-MLKL-Associated Necroptosis ....pdfBarbosa LA RIPK1-RIPK3-MLKL-Associated Necroptosis 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| dc.title.pt_BR.fl_str_mv |
RIPK1-RIPK3-MLKL-Associated Necroptosis Drives Leishmania infantum Killing in Neutrophils |
| title |
RIPK1-RIPK3-MLKL-Associated Necroptosis Drives Leishmania infantum Killing in Neutrophils |
| spellingShingle |
RIPK1-RIPK3-MLKL-Associated Necroptosis Drives Leishmania infantum Killing in Neutrophils Barbosa, Laiana Arlego Leishmania infantum Neutrófilos Necroptose Morte celular RIPK3 Linhagem mista parecida com domínio quinase Caspase-8 Leishmania infantum Neutrophils Necroptosis Cell death RIPK3 Mixed lineage kinase domain-like Caspase-8 |
| title_short |
RIPK1-RIPK3-MLKL-Associated Necroptosis Drives Leishmania infantum Killing in Neutrophils |
| title_full |
RIPK1-RIPK3-MLKL-Associated Necroptosis Drives Leishmania infantum Killing in Neutrophils |
| title_fullStr |
RIPK1-RIPK3-MLKL-Associated Necroptosis Drives Leishmania infantum Killing in Neutrophils |
| title_full_unstemmed |
RIPK1-RIPK3-MLKL-Associated Necroptosis Drives Leishmania infantum Killing in Neutrophils |
| title_sort |
RIPK1-RIPK3-MLKL-Associated Necroptosis Drives Leishmania infantum Killing in Neutrophils |
| author |
Barbosa, Laiana Arlego |
| author_facet |
Barbosa, Laiana Arlego Fiuza, Paloma Peixoto dos Santos Borges, Letícia J Rolim, Fellipe A Andrade, Mayara B Luz, Nivea Farias Carvalho, Graziele Quintela de Lima, Jonilson Berlink Almeida, Roque Pacheco de Chan, Francis K Bozza, Marcelo Torres Borges, Valeria de Matos Prates, Deboraci Brito |
| author_role |
author |
| author2 |
Fiuza, Paloma Peixoto dos Santos Borges, Letícia J Rolim, Fellipe A Andrade, Mayara B Luz, Nivea Farias Carvalho, Graziele Quintela de Lima, Jonilson Berlink Almeida, Roque Pacheco de Chan, Francis K Bozza, Marcelo Torres Borges, Valeria de Matos Prates, Deboraci Brito |
| author2_role |
author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Barbosa, Laiana Arlego Fiuza, Paloma Peixoto dos Santos Borges, Letícia J Rolim, Fellipe A Andrade, Mayara B Luz, Nivea Farias Carvalho, Graziele Quintela de Lima, Jonilson Berlink Almeida, Roque Pacheco de Chan, Francis K Bozza, Marcelo Torres Borges, Valeria de Matos Prates, Deboraci Brito |
| dc.subject.other.pt_BR.fl_str_mv |
Leishmania infantum Neutrófilos Necroptose Morte celular RIPK3 Linhagem mista parecida com domínio quinase Caspase-8 |
| topic |
Leishmania infantum Neutrófilos Necroptose Morte celular RIPK3 Linhagem mista parecida com domínio quinase Caspase-8 Leishmania infantum Neutrophils Necroptosis Cell death RIPK3 Mixed lineage kinase domain-like Caspase-8 |
| dc.subject.en.pt_BR.fl_str_mv |
Leishmania infantum Neutrophils Necroptosis Cell death RIPK3 Mixed lineage kinase domain-like Caspase-8 |
| description |
Fundação de Amparo à Pesquisa do Estado da Bahia-FAPESB (JCB0047/2013 to DP, 5760/2015 to VB) and from Conselho Nacional de Desenvolvimento Científico e Tecnológico-CNPq (482722/2013-4 to DP, 552721/2011-5 and 019.203.02712/2009-8 FAPITEC/CNPq to RA). RA also received a grant from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES: 23038. 005304/2011-01). NFL received funding from CAPES (grants 88887.142000/2017-00 and 88887.137958/2017-00). FC is supported by NIH grant AI119030. LAB and LJB received a fellowship from CNPq |
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2018 |
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2018-09-20T14:02:59Z |
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2018-09-20T14:02:59Z |
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2018 |
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BARBOSA, L. A. et al. RIPK1-RIPK3-MLKL-Associated Necroptosis Drives Leishmania infantum Killing in Neutrophils. Frontiers in Immunology, v. 9, 1918. |
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https://www.arca.fiocruz.br/handle/icict/28935 |
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1664-3224 |
| dc.identifier.doi.none.fl_str_mv |
10.3389/fimmu.2018.01818 |
| identifier_str_mv |
BARBOSA, L. A. et al. RIPK1-RIPK3-MLKL-Associated Necroptosis Drives Leishmania infantum Killing in Neutrophils. Frontiers in Immunology, v. 9, 1918. 1664-3224 10.3389/fimmu.2018.01818 |
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Frontiers Media |
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