Normal responses to specific NOD1-activating peptidoglycan agonists in the presence of the NOD2 frameshift and other mutations in Crohn's disease

European Journal of Immunology
David A van HeelRaymond J Playford

Abstract

Both NOD2/CARD15 alleles are mutated in approximately 10% of Crohn's disease patients, causing loss of functional responses to low-dose muropeptide agonists. We hypothesized that NOD2 mutations may also impair NOD1/CARD4 responses, supported by data suggesting NOD2 1007fs/1007fs patients had reduced responses to a putative NOD1 agonist, diaminopimelic acid-containing muramyl tripeptide (M-TriDAP). We measured peripheral blood mononuclear cell (n = 8 NOD2 wild type, n = 4 1007fs/1007fs, n = 6 702Trp/1007fs, n = 5 702Trp/702Trp, n = 3 908Arg/1007fs) responses to NOD1 agonists alone (IL-8/TNF-alpha), and agonist enhancement of lipopolysaccharide (LPS) responses (IL-1beta). Significant responses were seen with M-TriDAP at 10 nM (as with NOD2 agonists), but only at > or =100 nM with FK565/TriDAP. M-TriDAP induced IL-8/TNF-alpha secretion, and enhancement of LPS IL-1beta responses was significantly reduced between NOD2 double mutation carriers versus healthy controls, whereas there was no difference with FK565 or TriDAP stimulation, or between 1007fs/1007fs cells and other genotypes. M-TriDAP contains both NOD1 (gamma-D-Glu-mesoDAP) and NOD2 (MurNAc-L-Ala-D-Glu) minimal structures whereas FK565/TriDAP contain only NOD1 activating str...Continue Reading

References

Nov 1, 1984·Infection and Immunity·M W Vermeulen, G R Gray
Jul 6, 2000·The Journal of Biological Chemistry·N InoharaG Núñez
Nov 4, 2000·The Journal of Biological Chemistry·N InoharaG Nuñez
Mar 21, 2002·Proceedings of the National Academy of Sciences of the United States of America·Andrew I SuJohn B Hogenesch
Jan 7, 2003·The Journal of Biological Chemistry·Naohiro InoharaGabriel Nuñez
Jun 7, 2003·Science·Stephen E GirardinDana J Philpott
Jul 23, 2003·The Journal of Biological Chemistry·Stephen E GirardinDominique Mengin-Lecreulx
Apr 13, 2004·Proceedings of the National Academy of Sciences of the United States of America·Andrew I SuJohn B Hogenesch
Sep 14, 2004·Oncogene·Jerry UsaryCharles M Perou
Jul 16, 2005·European Journal of Immunology·David A van HeelRaymond J Playford
Jan 19, 2006·The Journal of Experimental Medicine·Junya MasumotoNaohiro Inohara

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Citations

Jan 9, 2007·Inflammatory Bowel Diseases·Johan Van LimbergenJack Satsangi
Jan 20, 2007·American Journal of Respiratory and Critical Care Medicine·Neil CartwrightJane A Mitchell
Oct 3, 2006·European Journal of Immunology·Gerben FerwerdaMihai G Netea
Nov 27, 2007·Annals of Medicine·Leticia A M CarneiroStephen E Girardin

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