Normand, Sylvain, Waldschmitt, Nadine, Neerincx, Andreas, Martinez-Torres, Ruben Julio, Chauvin, Camille, Couturier-Maillard, Aurelie, Boulard, Olivier, Cobret, Laetitia, Awad, Fawaz, Huot, Ludovic, Ribeiro-Ribeiro, Andre, Lautz, Katja, Ruez, Richard ORCID: 0000-0001-5187-2210, Delacre, Myriam, Bondu, Clovis, Guilliams, Martin, Scott, Charlotte, Segal, Anthony, Amselem, Serge, Hot, David ORCID: 0000-0002-2361-0616, Karabina, Sonia, Bohn, Erwin, Ryffel, Bernhard, Poulin, Lionel F., Kufer, Thomas A. and Chamaillard, Mathias ORCID: 0000-0002-0243-9717 (2018). Proteasomal degradation of NOD2 by NLRP12 in monocytes promotes bacterial tolerance and colonization by enteropathogens. Nat. Commun., 9. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

Full text not available from this repository.

Abstract

Mutations in the nucleotide-binding oligomerization domain protein 12 (NLRP12) cause recurrent episodes of serosal inflammation. Here we show that NLRP12 efficiently sequesters HSP90 and promotes K48-linked ubiquitination and degradation of NOD2 in response to bacterial muramyl dipeptide (MDP). This interaction is mediated by the linker-region proximal to the nucleotide-binding domain of NLRP12. Consequently, the disease-causing NLRP12 R284X mutation fails to repress MDP-induced NF-kappa B and subsequent activity of the JAK/STAT signaling pathway. While NLRP12 deficiency renders septic mice highly susceptible towards MDP, a sustained sensing of MDP through NOD2 is observed among monocytes lacking NLRP12. This loss of tolerance in monocytes results in greater colonization resistance towards Citrobacter rodentium. Our data show that this is a consequence of NOD2-dependent accumulation of inflammatory mononuclear cells that correlates with induction of interferon-stimulated genes. Our study unveils a relevant process of tolerance towards the gut microbiota that is exploited by an attaching/effacing enteric pathogen.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Normand, SylvainUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Waldschmitt, NadineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neerincx, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martinez-Torres, Ruben JulioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chauvin, CamilleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Couturier-Maillard, AurelieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boulard, OlivierUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cobret, LaetitiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Awad, FawazUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huot, LudovicUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ribeiro-Ribeiro, AndreUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lautz, KatjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ruez, RichardUNSPECIFIEDorcid.org/0000-0001-5187-2210UNSPECIFIED
Delacre, MyriamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bondu, ClovisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guilliams, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scott, CharlotteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Segal, AnthonyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Amselem, SergeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hot, DavidUNSPECIFIEDorcid.org/0000-0002-2361-0616UNSPECIFIED
Karabina, SoniaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bohn, ErwinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ryffel, BernhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Poulin, Lionel F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kufer, Thomas A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chamaillard, MathiasUNSPECIFIEDorcid.org/0000-0002-0243-9717UNSPECIFIED
URN: urn:nbn:de:hbz:38-161928
DOI: 10.1038/s41467-018-07750-5
Journal or Publication Title: Nat. Commun.
Volume: 9
Date: 2018
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2041-1723
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ATTENUATES COLON INFLAMMATION; CITROBACTER-RODENTIUM; DENDRITIC CELLS; SENSORS NOD1; ACTIVATION; EXPRESSION; MUTATIONS; MONARCH-1; ATG16L1; PROTEINMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/16192

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item