BAD-LAMP controls TLR9 trafficking and signalling in human plasmacytoid dendritic cells

Detalhes bibliográficos
Autor(a) principal: Combes, Alexis
Data de Publicação: 2017
Outros Autores: Camosseto, Voahirana, N'Guessan, Prudence, Argüello, Rafael J., Mussard, Julie, Caux, Christophe, Bendriss-Vermare, Nathalie, Pierre, Philippe, Gatti, Evelina
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10773/27363
Resumo: Toll-like receptors (TLR) are essential components of the innate immune system. Several accessory proteins, such as UNC93B1, are required for transport and activation of nucleic acid sensing Toll-like receptors in endosomes. Here, we show that BAD-LAMP (LAMP5) controls TLR9 trafficking to LAMP1+ late endosomes in human plasmacytoid dendritic cells (pDC), leading to NF-κB activation and TNF production upon DNA detection. An inducible VAMP3+/LAMP2+/LAMP1- endolysosome compartment exists in pDCs from which TLR9 activation triggers type I interferon expression. BAD-LAMP-silencing enhances TLR9 retention in this compartment and consequent downstream signalling events. Conversely, sustained BAD-LAMP expression in pDCs contributes to their lack of type I interferon production after exposure to a TGF-β-positive microenvironment or isolation from human breast tumours. Hence, BAD-LAMP limits interferon expression in pDCs indirectly, by promoting TLR9 sorting to late endosome compartments at steady state and in response to immunomodulatory cues.TLR9 is highly expressed by plasmacytoid dendritic cells and detects nucleic acids, but to discriminate between host and microbial nucleic acids TLR9 is sorted into different endosomal compartments. Here the authors show that BAD-LAMP limits type 1 interferon responses by sorting TLR9 to late endosomal compartments.
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spelling BAD-LAMP controls TLR9 trafficking and signalling in human plasmacytoid dendritic cellsCell Line, TumorCells, CulturedDendritic CellsEndosomesHumansInterferon Type ILysosomal-Associated Membrane Protein 2Lysosome-Associated Membrane GlycoproteinsMicroscopy, ConfocalNF-kappa BProtein TransportRNA InterferenceToll-Like Receptor 9Transforming Growth Factor betaVesicle-Associated Membrane Protein 3Signal TransductionToll-like receptors (TLR) are essential components of the innate immune system. Several accessory proteins, such as UNC93B1, are required for transport and activation of nucleic acid sensing Toll-like receptors in endosomes. Here, we show that BAD-LAMP (LAMP5) controls TLR9 trafficking to LAMP1+ late endosomes in human plasmacytoid dendritic cells (pDC), leading to NF-κB activation and TNF production upon DNA detection. An inducible VAMP3+/LAMP2+/LAMP1- endolysosome compartment exists in pDCs from which TLR9 activation triggers type I interferon expression. BAD-LAMP-silencing enhances TLR9 retention in this compartment and consequent downstream signalling events. Conversely, sustained BAD-LAMP expression in pDCs contributes to their lack of type I interferon production after exposure to a TGF-β-positive microenvironment or isolation from human breast tumours. Hence, BAD-LAMP limits interferon expression in pDCs indirectly, by promoting TLR9 sorting to late endosome compartments at steady state and in response to immunomodulatory cues.TLR9 is highly expressed by plasmacytoid dendritic cells and detects nucleic acids, but to discriminate between host and microbial nucleic acids TLR9 is sorted into different endosomal compartments. Here the authors show that BAD-LAMP limits type 1 interferon responses by sorting TLR9 to late endosomal compartments.Nature Research2020-01-24T18:21:04Z2017-10-13T00:00:00Z2017-10-13info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10773/27363eng10.1038/s41467-017-00695-1Combes, AlexisCamosseto, VoahiranaN'Guessan, PrudenceArgüello, Rafael J.Mussard, JulieCaux, ChristopheBendriss-Vermare, NathaliePierre, PhilippeGatti, Evelinainfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-02-22T11:47:05Zoai:ria.ua.pt:10773/27363Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T02:57:47.287696Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv BAD-LAMP controls TLR9 trafficking and signalling in human plasmacytoid dendritic cells
title BAD-LAMP controls TLR9 trafficking and signalling in human plasmacytoid dendritic cells
spellingShingle BAD-LAMP controls TLR9 trafficking and signalling in human plasmacytoid dendritic cells
Combes, Alexis
Cell Line, Tumor
Cells, Cultured
Dendritic Cells
Endosomes
Humans
Interferon Type I
Lysosomal-Associated Membrane Protein 2
Lysosome-Associated Membrane Glycoproteins
Microscopy, Confocal
NF-kappa B
Protein Transport
RNA Interference
Toll-Like Receptor 9
Transforming Growth Factor beta
Vesicle-Associated Membrane Protein 3
Signal Transduction
title_short BAD-LAMP controls TLR9 trafficking and signalling in human plasmacytoid dendritic cells
title_full BAD-LAMP controls TLR9 trafficking and signalling in human plasmacytoid dendritic cells
title_fullStr BAD-LAMP controls TLR9 trafficking and signalling in human plasmacytoid dendritic cells
title_full_unstemmed BAD-LAMP controls TLR9 trafficking and signalling in human plasmacytoid dendritic cells
title_sort BAD-LAMP controls TLR9 trafficking and signalling in human plasmacytoid dendritic cells
author Combes, Alexis
author_facet Combes, Alexis
Camosseto, Voahirana
N'Guessan, Prudence
Argüello, Rafael J.
Mussard, Julie
Caux, Christophe
Bendriss-Vermare, Nathalie
Pierre, Philippe
Gatti, Evelina
author_role author
author2 Camosseto, Voahirana
N'Guessan, Prudence
Argüello, Rafael J.
Mussard, Julie
Caux, Christophe
Bendriss-Vermare, Nathalie
Pierre, Philippe
Gatti, Evelina
author2_role author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Combes, Alexis
Camosseto, Voahirana
N'Guessan, Prudence
Argüello, Rafael J.
Mussard, Julie
Caux, Christophe
Bendriss-Vermare, Nathalie
Pierre, Philippe
Gatti, Evelina
dc.subject.por.fl_str_mv Cell Line, Tumor
Cells, Cultured
Dendritic Cells
Endosomes
Humans
Interferon Type I
Lysosomal-Associated Membrane Protein 2
Lysosome-Associated Membrane Glycoproteins
Microscopy, Confocal
NF-kappa B
Protein Transport
RNA Interference
Toll-Like Receptor 9
Transforming Growth Factor beta
Vesicle-Associated Membrane Protein 3
Signal Transduction
topic Cell Line, Tumor
Cells, Cultured
Dendritic Cells
Endosomes
Humans
Interferon Type I
Lysosomal-Associated Membrane Protein 2
Lysosome-Associated Membrane Glycoproteins
Microscopy, Confocal
NF-kappa B
Protein Transport
RNA Interference
Toll-Like Receptor 9
Transforming Growth Factor beta
Vesicle-Associated Membrane Protein 3
Signal Transduction
description Toll-like receptors (TLR) are essential components of the innate immune system. Several accessory proteins, such as UNC93B1, are required for transport and activation of nucleic acid sensing Toll-like receptors in endosomes. Here, we show that BAD-LAMP (LAMP5) controls TLR9 trafficking to LAMP1+ late endosomes in human plasmacytoid dendritic cells (pDC), leading to NF-κB activation and TNF production upon DNA detection. An inducible VAMP3+/LAMP2+/LAMP1- endolysosome compartment exists in pDCs from which TLR9 activation triggers type I interferon expression. BAD-LAMP-silencing enhances TLR9 retention in this compartment and consequent downstream signalling events. Conversely, sustained BAD-LAMP expression in pDCs contributes to their lack of type I interferon production after exposure to a TGF-β-positive microenvironment or isolation from human breast tumours. Hence, BAD-LAMP limits interferon expression in pDCs indirectly, by promoting TLR9 sorting to late endosome compartments at steady state and in response to immunomodulatory cues.TLR9 is highly expressed by plasmacytoid dendritic cells and detects nucleic acids, but to discriminate between host and microbial nucleic acids TLR9 is sorted into different endosomal compartments. Here the authors show that BAD-LAMP limits type 1 interferon responses by sorting TLR9 to late endosomal compartments.
publishDate 2017
dc.date.none.fl_str_mv 2017-10-13T00:00:00Z
2017-10-13
2020-01-24T18:21:04Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10773/27363
url http://hdl.handle.net/10773/27363
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 10.1038/s41467-017-00695-1
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Research
publisher.none.fl_str_mv Nature Research
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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