{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:38:59Z","timestamp":1791225539491,"version":"4.1.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2015,2,16]],"date-time":"2015-02-16T00:00:00Z","timestamp":1424044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100003035","name":"Aase og Ejnar Danielsens Fond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003035","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Axel Muusfeldts Foundation"},{"name":"Direkt\u00c3\u00b8r Kurt B\u00c3\u00b8nnelyck og hustru fru Grethe B\u00c3\u00b8nnelyckes Foundation"},{"name":"Else og Mogens Wedell-Wedellsborgs Foundation"},{"name":"Holger og Ruth Hesses Mindefond"},{"DOI":"10.13039\/501100008267","name":"Kong Christian Den Tiendes Fond","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008267","id-type":"DOI","asserted-by":"crossref"}]},{"name":"P. A. Messerchmidt og Hustrus Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,2,16]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>Recognition of bacterial peptidoglycan-derived muramyl-dipeptide (MDP) by nucleotide oligomerization domain 2 (NOD2) induces crucial innate immune responses. Most bacteria carry the N-acetylated form of MDP (A-MDP) in their cell membranes, whereas N-glycolyl MDP (G-MDP) is typical for mycobacteria. Experimental murine studies have reported G-MDP to have a greater NOD2-stimulating capacity than A-MDP. As NOD2 polymorphisms are associated with Crohn's disease (CD), a link has been suggested between mycobacterial infections and CD. Thus, the aim was to investigate if NOD2 responses are dependent upon type of MDP and further to determine the role of NOD2 gene variants for the bacterial recognition in CD. The response pattern to A-MDP, G-MDP, Mycobacterium segmatis (expressing mainly G-MDP) and M. segmatis\u0394namH (expressing A-MDP), Listeria monocytogenes (LM) (an A-MDP-containing bacteria) and M. avium paratuberculosis (MAP) (a G-MDP-containing bacteria associated with CD) was investigated in human peripheral blood mononuclear cells (PBMCs). A-MDP and M. segmatis\u0394namH induced significantly higher tumour necrosis factor (TNF)-\u03b1 protein levels in healthy wild-type NOD2\u2005PBMCs compared with G-MDP and M. segmatis. NOD2 mutations resulted in a low tumour necrosis factor (TNF)-\u03b1 protein secretion following stimulation with LM. Contrary to this, TNF-\u03b1 levels were unchanged upon MAP stimulation regardless of NOD2 genotype and MAP solely activated NOD2- and Toll-like receptor (TLRs)-pathway with an enhanced production of interleukin (IL)-1\u03b2 and IL-10. In conclusion, the results indicate that CD-associated NOD2 deficiencies might affect the response towards a broader array of commensal and pathogenic bacteria expressing A-MDP, whereas they attenuate the role of mycobacteria in the pathogenesis of CD.<\/jats:p>","DOI":"10.1111\/cei.12471","type":"journal-article","created":{"date-parts":[[2014,10,22]],"date-time":"2014-10-22T04:45:39Z","timestamp":1413953139000},"page":"426-434","source":"Crossref","is-referenced-by-count":23,"title":["Species-specific engagement of human nucleotide oligomerization domain 2 (NOD)2 and Toll-like receptor (TLR) signalling upon intracellular bacterial infection: role of Crohn's associated NOD2 gene variants"],"prefix":"10.1093","volume":"179","author":[{"given":"M","family":"Salem","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J 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