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dc.contributor.authorBabdor, Joel
dc.contributor.authorDescamps, Delphyne
dc.contributor.authorAdiko, Aimé Cézaire
dc.contributor.authorTohmé, Mira
dc.contributor.authorMaschalidi, Sophia
dc.contributor.authorEvnouchidou, Irini
dc.contributor.authorVasconcellos, Luiz Ricardo
dc.contributor.authorDe Luca, Mariacristina
dc.contributor.authorMauvais, Francois-Xavier
dc.contributor.authorGarfa-Traore, Meriem
dc.contributor.authorBrinkmann, Melanie M
dc.contributor.authorChignard, Michel
dc.contributor.authorManoury, Bénédicte
dc.contributor.authorSaveanu, Loredana
dc.date.accessioned2018-01-08T11:50:07Z
dc.date.available2018-01-08T11:50:07Z
dc.date.issued2017-05
dc.identifier.citationIRAP+ endosomes restrict TLR9 activation and signaling. 2017, 18 (5):509-518 Nat. Immunol.en
dc.identifier.issn1529-2916
dc.identifier.pmid28319098
dc.identifier.doi10.1038/ni.3711
dc.identifier.urihttp://hdl.handle.net/10033/621226
dc.description.abstractThe retention of intracellular Toll-like receptors (TLRs) in the endoplasmic reticulum prevents their activation under basal conditions. TLR9 is activated by sensing ligands in specific endosomal-lysosomal compartments. Here we identified IRAP+ endosomes as major cellular compartments for the early steps of TLR9 activation in dendritic cells (DCs). Both TLR9 and its ligand, the dinucleotide CpG, were present as cargo in IRAP+ endosomes. In the absence of the aminopeptidase IRAP, the trafficking of CpG and TLR9 to lysosomes and signaling via TLR9 were enhanced in DCs and in mice following bacterial infection. IRAP stabilized CpG-containing endosomes by interacting with the actin-nucleation factor FHOD4, which slowed the trafficking of TLR9 toward lysosomes. Thus, endosomal retention of TLR9 via the interaction of IRAP with the actin cytoskeleton is a mechanism that prevents hyper-activation of TLR9 in DCs.
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshAnimalsen
dc.subject.meshCells, Cultureden
dc.subject.meshCpG Islandsen
dc.subject.meshCystinyl Aminopeptidaseen
dc.subject.meshCytoskeletonen
dc.subject.meshDendritic Cellsen
dc.subject.meshEndosomesen
dc.subject.meshMiceen
dc.subject.meshMice, Inbred C57BLen
dc.subject.meshMice, Knockouten
dc.subject.meshMutationen
dc.subject.meshOligodeoxyribonucleotidesen
dc.subject.meshProtein Bindingen
dc.subject.meshPseudomonas Infectionsen
dc.subject.meshPseudomonas aeruginosaen
dc.subject.meshSignal Transductionen
dc.subject.meshToll-Like Receptor 9en
dc.titleIRAP+ endosomes restrict TLR9 activation and signaling.en
dc.typeArticleen
dc.contributor.departmentHelmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalNature immunologyen
refterms.dateFOA2018-06-13T00:27:14Z
html.description.abstractThe retention of intracellular Toll-like receptors (TLRs) in the endoplasmic reticulum prevents their activation under basal conditions. TLR9 is activated by sensing ligands in specific endosomal-lysosomal compartments. Here we identified IRAP+ endosomes as major cellular compartments for the early steps of TLR9 activation in dendritic cells (DCs). Both TLR9 and its ligand, the dinucleotide CpG, were present as cargo in IRAP+ endosomes. In the absence of the aminopeptidase IRAP, the trafficking of CpG and TLR9 to lysosomes and signaling via TLR9 were enhanced in DCs and in mice following bacterial infection. IRAP stabilized CpG-containing endosomes by interacting with the actin-nucleation factor FHOD4, which slowed the trafficking of TLR9 toward lysosomes. Thus, endosomal retention of TLR9 via the interaction of IRAP with the actin cytoskeleton is a mechanism that prevents hyper-activation of TLR9 in DCs.


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