BAD-LAMP controls TLR9 trafficking and signalling in human plasmacytoid dendritic cells
Autor(a) principal: | |
---|---|
Data de Publicação: | 2017 |
Outros Autores: | , , , , , , , |
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. |
id |
RCAP_0533417a47fb622f9568f8d73101fcaa |
---|---|
oai_identifier_str |
oai:ria.ua.pt:10773/27363 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
7160 |
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 |
repository.mail.fl_str_mv |
|
_version_ |
1799137632552222720 |