Proteasomal degradation of NOD2 by NLRP12 in monocytes promotes bacterial tolerance and colonization by enteropathogens

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dc.contributor.authorNormand, Sylvain
dc.contributor.authorWaldschmitt, Nadine
dc.contributor.authorNeerincx, Andreas
dc.contributor.authorMartinez-Torres, Ruben Julio
dc.contributor.authorChauvin, Camille
dc.contributor.authorCouturier-Maillard, Aurélie
dc.contributor.authorBoulard, Olivier
dc.contributor.authorCobret, Laetitia
dc.contributor.authorAwad, Fawaz
dc.contributor.authorHuot, Ludovic
dc.contributor.authorRibeiro-Ribeiro, Andre
dc.contributor.authorLautz, Katja
dc.contributor.authorRuez, Richard
dc.contributor.authorDelacre, Myriam
dc.contributor.authorBondu, Clovis
dc.contributor.authorGuilliams, Martin
dc.contributor.authorScott, Charlotte
dc.contributor.authorSegal, Anthony
dc.contributor.authorAmselem, Serge
dc.contributor.authorHot, David
dc.contributor.authorKarabina, Sonia
dc.contributor.authorBohn, Erwin
dc.contributor.authorRyffel, Bernhard
dc.contributor.authorPoulin, Lionel F.
dc.contributor.authorKufer, Thomas A.
dc.contributor.authorChamaillard, Mathias
dc.date.accessioned2019-11-17T17:42:10Z
dc.date.available2019-11-17T17:42:10Z
dc.date.issued2018-12-17
dc.description.abstractMutations 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 nucleotidebinding domain of NLRP12. Consequently, the disease-causing NLRP12 R284X mutation fails to repress MDP-induced NF-κB 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.en_US
dc.description.sponsorshipWe thank Yvonne Postma for technical assistance.en_US
dc.identifier.citationNormand, S., Waldschmitt, N., Neerincx, A. et al. Proteasomal degradation of NOD2 by NLRP12 in monocytes promotes bacterial tolerance and colonization by enteropathogens. Nat Commun 9, 5338 (2018) doi:10.1038/s41467-018-07750-5en_US
dc.identifier.issn2041-1723
dc.identifier.urihttps://dspace.alquds.edu/handle/20.500.12213/4919
dc.language.isoenen_US
dc.publisherSpringeren_US
dc.titleProteasomal degradation of NOD2 by NLRP12 in monocytes promotes bacterial tolerance and colonization by enteropathogensen_US
dc.typeArticleen_US
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