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Journal articles
IRAP+ endosomes restrict TLR9 activation and signaling
Joël Babdor
1, 2, 3
Delphyne Descamps
1, 2, 3, 4
Adiko Assi Aimé Cézaire
5, 6
Mira Tohmé
1, 2, 3, 7
Sophia Maschalidi
8, 1, 2, 3
Irini Evnouchidou
5, 6
Luiz Ricardo Vasconcellos
1, 2, 9, 3
Mariacristina de Luca
5, 6
Francois-Xavier Mauvais
1, 2, 3
Meriem Garfa-Traore
1, 2, 3
Melanie Brinkmann
10
Michel Chignard
11, 2
Bénédicte Manoury
1, 2, 3, *
Loredana Saveanu
5, 6, *
*
Corresponding author
Joël Babdor 1, 2, 3
Author
Delphyne Descamps 1, 2, 3, 4
Author IdHAL : delphyne-descamps ResearcherId : http://www.researcherid.com/rid/3549867 IdRef : https://www.idref.fr/120011182 ORCID : https://orcid.org/0000-0002-4883-6910
Adiko Assi Aimé Cézaire 5, 6
Author
Mira Tohmé 1, 2, 3, 7
Author
Sophia Maschalidi 8, 1, 2, 3
Author
Irini Evnouchidou 5, 6
Author
Luiz Ricardo Vasconcellos 1, 2, 9, 3
Author
Mariacristina de Luca 5, 6
Author
Francois-Xavier Mauvais 1, 2, 3
Author
Meriem Garfa-Traore 1, 2, 3
Author
Melanie M Brinkmann 10
Author
Michel Chignard 11, 2
Author
Bénédicte Manoury 1, 2, 3
Correspondent author
Loredana Saveanu 5, 6
Correspondent author
1
INEM - UM 111 (UMR 8253 / U1151) - Institut Necker Enfants-Malades (Bâtiment Leriche
14 rue Maria Helena Vieira Da Silva
75014 Paris - France)
- UPD5 - Université Paris Descartes - Paris 5 : UM 111 (12, rue de l'École de Médecine - 75270 Paris cedex 06 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1151 (101, rue de Tolbiac, 75013 Paris - France)
- CNRS - Centre National de la Recherche Scientifique : UMR 8253 (France)
2
USPC - Université Sorbonne Paris Cité (Université Sorbonne Paris Cité | 100-104, avenue de France | 75013 Paris - France)
3
UPD5 Médecine - Université Paris Descartes - Faculté de Médecine (15 rue de l'École de médecine - 75270 Paris Cedex 06 - France)
- UPD5 - Université Paris Descartes - Paris 5 (12, rue de l'École de Médecine - 75270 Paris cedex 06 - France)
4
VIM (UR 0892) - Unité de recherche Virologie et Immunologie Moléculaires (INRA Centre de Recherche de Jouy-en-Josas F-78352 Jouy-en-Josas cedex - France)
- INRA - Institut National de la Recherche Agronomique : UR0892 (France)
5
CRI (UMR_S_1149 / ERL_8252 / U1149) - Centre de recherche sur l'Inflammation (Faculté de Médecine site Bichat - 16, Rue Henri Huchard - BP 416/4ème étage - 75870 Paris Cedex 18 - France)
- UPD7 - Université Paris Diderot - Paris 7 : UMR_S_1149 (5 rue Thomas-Mann - 75205 Paris cedex 13 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1149 (101, rue de Tolbiac, 75013 Paris - France)
- CNRS - Centre National de la Recherche Scientifique : ERL_8252 (France)
6
Faculté de Médecine Xavier Bichat (75018, Paris, France - France)
- UPD7 - Université Paris Diderot - Paris 7 (5 rue Thomas-Mann - 75205 Paris cedex 13 - France)
7
Department of Pediatrics - Division of Immunology [Boston, Massachusetts, USA] (Harvard Medical School - 25 Shattuck Street - Boston, MA 02115. - United States)
- HMS - Harvard Medical School [Boston] (25 Shattuck Street Boston, MA 02115 - United States)
- Boston Children's Hospital (300 Longwood Ave, Boston, MA 02115 - United States)
8
IMAGINE - U1163 - Imagine - Institut des maladies génétiques (IHU Imagine,
156 rue de Vaugirard, 75015 PARIS
et
24 Boulevard du Montparnasse, 75015 Paris - France)
- CNRS - Centre National de la Recherche Scientifique (France)
- UPD5 - Université Paris Descartes - Paris 5 : UMR_S 1163 (12, rue de l'École de Médecine - 75270 Paris cedex 06 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1163 (101, rue de Tolbiac, 75013 Paris - France)
9
Laboratório de Imunoreceptores e Sinalização [Rio de Janeiro, Brazil] (Av. Carlos Chagas Filho, 373 - G1-019 - Ilha do Fundão, Rio de Janeiro - RJ, 21941-902, Brésil. - Brazil)
- IBCCF / UFRJ - Instituto de Biofísica Carlos Chagas Filho [Rio de Janeiro] (Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373 - G1-019 - Ilha do Fundão, Rio de Janeiro - RJ, 21941-902 - Brazil)
- UFRJ - Universidade Federal do Rio de Janeiro (Av. Pedro Calmon, 550 - Cidade Universitária, Rio de Janeiro - RJ, 21941-901 - Brazil)
- UFRJ - Universidade Federal do Rio de Janeiro (Av. Pedro Calmon, 550 - Cidade Universitária, Rio de Janeiro - RJ, 21941-901 - Brazil)
10
HZI - Helmholtz Centre for Infection Research (Inhoffenstraße 7, 38124 Braunschweig - Germany)
11
CR Saint-Antoine - Centre de Recherche Saint-Antoine (France)
- UPMC - Université Pierre et Marie Curie - Paris 6 (4 place Jussieu - 75005 Paris - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U938 (101, rue de Tolbiac, 75013 Paris - France)
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.
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Journal articles
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https://www.hal.inserm.fr/inserm-01674784
Contributor : Loredana Saveanu <>
Submitted on : Wednesday, January 3, 2018 - 4:04:43 PM
Last modification on : Tuesday, March 2, 2021 - 3:56:02 PM
Long-term archiving on: : Thursday, May 3, 2018 - 2:04:47 PM
Contributor : Loredana Saveanu <>
Submitted on : Wednesday, January 3, 2018 - 4:04:43 PM
Last modification on : Tuesday, March 2, 2021 - 3:56:02 PM
Long-term archiving on: : Thursday, May 3, 2018 - 2:04:47 PM
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Identifiers
- HAL Id : inserm-01674784, version 1
- PUBMED : 28319098
- DOI : 10.1038/ni.3711
- WOS : 000399378700008
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INSERM | CNRS | INRA | UPMC | USPC | U938 | UNIV-PARIS5 | SORBONNE-UNIVERSITE | SU-MEDECINE | UNIV-PARIS7 | INRAE | UNIV-PARIS | UP-SANTE | SU-TI
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⟩
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