Skip to Main content Skip to Navigation
Journal articles

IRAP+ endosomes restrict TLR9 activation and signaling

Abstract : The 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.
Document type :
Journal articles
Complete list of metadatas

Cited literature [28 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-01674784
Contributor : Loredana Saveanu <>
Submitted on : Wednesday, January 3, 2018 - 4:04:43 PM
Last modification on : Monday, May 18, 2020 - 4:50:34 PM
Long-term archiving on: : Thursday, May 3, 2018 - 2:04:47 PM

Identifiers

Citation

Joël Babdor, Delphyne Descamps, Adiko Assi Aimé Cézaire, Mira Tohmé, Sophia Maschalidi, et al.. IRAP+ endosomes restrict TLR9 activation and signaling. Nature Immunology, Nature Publishing Group, 2017, 18 (5), pp.509-518. ⟨10.1038/ni.3711⟩. ⟨inserm-01674784⟩

Share

Metrics

Record views

775

Files downloads

1037