| Literature DB >> 28319098 |
Joel Babdor1,2,3, Delphyne Descamps1,2,3,4, Aimé Cézaire Adiko5,6, Mira Tohmé1,2,3,7, Sophia Maschalidi1,2,3,8, Irini Evnouchidou5,6, Luiz Ricardo Vasconcellos1,2,3,9, Mariacristina De Luca5,6, Francois-Xavier Mauvais1,2,3, Meriem Garfa-Traore1,2,3, Melanie M Brinkmann10, Michel Chignard11,12, Bénédicte Manoury1,2,3, Loredana Saveanu5,6.
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.Entities:
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Year: 2017 PMID： 28319098 DOI： 10.1038/ni.3711
Source DB: PubMed Journal: Nat Immunol ISSN： 1529-2908 Impact factor: 25.606