Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection
- PMID: 12527755
- DOI: 10.1074/jbc.C200651200
Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection
Abstract
Nod2 activates the NF-kappaB pathway following intracellular stimulation by bacterial products. Recently, mutations in Nod2 have been shown to be associated with Crohn's disease, suggesting a role for bacteria-host interactions in the etiology of this disorder. We show here that Nod2 is a general sensor of peptidoglycan through the recognition of muramyl dipeptide (MDP), the minimal bioactive peptidoglycan motif common to all bacteria. Moreover, the 3020insC frameshift mutation, the most frequent Nod2 variant associated with Crohn's disease patients, fully abrogates Nod2-dependent detection of peptidoglycan and MDP. Together, these results impact on the understanding of Crohn's disease development. Additionally, the characterization of Nod2 as the first pathogen-recognition molecule that detects MDP will help to unravel the well known biological activities of this immunomodulatory compound.
Similar articles
-
Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn's disease.J Biol Chem. 2003 Feb 21;278(8):5509-12. doi: 10.1074/jbc.C200673200. Epub 2003 Jan 4. J Biol Chem. 2003. PMID: 12514169
-
The frameshift mutation in Nod2 results in unresponsiveness not only to Nod2- but also Nod1-activating peptidoglycan agonists.J Biol Chem. 2005 Oct 28;280(43):35859-67. doi: 10.1074/jbc.M504924200. Epub 2005 Aug 22. J Biol Chem. 2005. PMID: 16115863
-
NOD2 3020insC mutation and the pathogenesis of Crohn's disease: impaired IL-1beta production points to a loss-of-function phenotype.Neth J Med. 2005 Sep;63(8):305-8. Neth J Med. 2005. PMID: 16186640
-
Muramyl dipeptide responsive pathways in Crohn's disease: from NOD2 and beyond.Cell Mol Life Sci. 2013 Sep;70(18):3391-404. doi: 10.1007/s00018-012-1246-4. Epub 2012 Dec 29. Cell Mol Life Sci. 2013. PMID: 23275943 Free PMC article. Review.
-
Innate immune sensing of microbes by Nod proteins.Ann N Y Acad Sci. 2006 Aug;1072:19-27. doi: 10.1196/annals.1326.020. Ann N Y Acad Sci. 2006. PMID: 17057187 Review.
Cited by
-
Muropeptides and muropeptide transporters impact on host immune response.Gut Microbes. 2024 Jan-Dec;16(1):2418412. doi: 10.1080/19490976.2024.2418412. Epub 2024 Oct 22. Gut Microbes. 2024. PMID: 39439228 Free PMC article. Review.
-
Clinical phenotype, NOD2 genotypes, and treatment observations in Yao syndrome: a retrospective case series.Front Immunol. 2024 Oct 4;15:1304792. doi: 10.3389/fimmu.2024.1304792. eCollection 2024. Front Immunol. 2024. PMID: 39430755 Free PMC article.
-
RIPK2 is crucial for the microglial inflammatory response to bacterial muramyl dipeptide but not to lipopolysaccharide.bioRxiv [Preprint]. 2024 Oct 12:2024.10.09.617444. doi: 10.1101/2024.10.09.617444. bioRxiv. 2024. PMID: 39416057 Free PMC article. Preprint.
-
Bacteria and Allergic Diseases.Int J Mol Sci. 2024 Sep 25;25(19):10298. doi: 10.3390/ijms251910298. Int J Mol Sci. 2024. PMID: 39408628 Free PMC article. Review.
-
Deubiquitination of RIPK2 by OTUB2 augments NOD2 signalling and protective effects in intestinal inflammation.Clin Transl Med. 2024 Oct;14(10):e70038. doi: 10.1002/ctm2.70038. Clin Transl Med. 2024. PMID: 39358938 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases