{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T18:29:49Z","timestamp":1791052189223,"version":"4.1.0"},"reference-count":15,"publisher":"MathDoc\/Centre Mersenne","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Innate immunity relies on the detection of microbial invaders by two distinct systems. One system comprises a family of membrane-bound receptors, termed the Toll-like receptors, while the other family, termed the nucleotide-binding site\/leucine-rich repeat (NBS\/LRR) proteins, consists of molecules that are found in the cytoplasmic compartment. These two detection systems recognize conserved molecular components of microbes including such structural motifs as lipopolysaccharide from the Gram-negative bacterial cell wall and peptidoglycan (PGN) found in the cell wall of both Gram-negative and Gram-positive bacteria. This review focuses on two members of the NBS\/LRR family of proteins, Nod1 and Nod2. Recently, the microbial motifs sensed by these two molecules have been characterized. Both Nod1 and Nod2 recognize PGN, however, each requires distinct molecular motifs to attain sensing. Nod1 recognizes a naturally occurring muropeptide of PGN that presents a unique amino acid at its terminus called diaminopilemic acid (DAP). This amino acid is found mainly in the PGN of Gram-negative bacteria designating Nod1 as a sensor of Gram-negative bacteria. In contrast, Nod2 can detect the minimal bioactive fragment of PGN, called muramyl dipeptide. Thus Nod2 is a general sensor of bacterial PGN. Since mutations in the gene encoding Nod2 were recently shown to be associated with the chronic inflammatory disease, Crohn's disease, these results are discussed in the context of how disrupting the interplay between host detection and bacterial aggression may lead to inflammatory diseases.<\/jats:p>","DOI":"10.1016\/j.crvi.2004.02.010","type":"journal-article","created":{"date-parts":[[2004,5,30]],"date-time":"2004-05-30T18:53:51Z","timestamp":1085943231000},"page":"551-555","source":"Crossref","is-referenced-by-count":38,"title":["Nods and \u2018intracellular\u2019 innate immunity"],"prefix":"10.5802","volume":"327","author":[{"given":"J\u00e9r\u00f4me","family":"Viala","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Sansonetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana J.","family":"Philpott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"3842","published-online":{"date-parts":[[2004,5,25]]},"reference":[{"key":"key2025102316252688958_1","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/S0952-7915(98)80024-1","article-title":"An ancient system of host defense","volume":"10","author":"Medzhitov, R.","year":"1998","unstructured":"[1] Medzhitov, R.; Janeway, C.A. Jr. An ancient system of host defense, Curr. Opin. Immunol., Volume 10 (1998), pp. 12-15","journal-title":"Curr. Opin. Immunol."},{"key":"key2025102316252688958_2","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/35100529","article-title":"Toll-like receptors and innate immunity","volume":"1","author":"Medzhitov, R.","year":"2001","unstructured":"[2] Medzhitov, R. Toll-like receptors and innate immunity, Nat. Rev. Immunol., Volume 1 (2001), pp. 135-145","journal-title":"Nat. Rev. Immunol."},{"key":"key2025102316252688958_3","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1046\/j.1462-5822.2003.00304.x","article-title":"Nods, Nalps and Naip: intracellular regulators of bacterial-induced inflammation","volume":"5","author":"Chamaillard, M.","year":"2003","unstructured":"[3] Chamaillard, M.; Girardin, S.E.; Viala, J.; Philpott, D.J. Nods, Nalps and Naip: intracellular regulators of bacterial-induced inflammation, Cell. Microbiol., Volume 5 (2003), pp. 581-592","journal-title":"Cell. Microbiol."},{"key":"key2025102316252688958_4","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/nri1086","article-title":"NODs: intracellular proteins involved in inflammation and apoptosis","volume":"3","author":"Inohara, N.","year":"2003","unstructured":"[4] Inohara, N.; Nunez, G. NODs: intracellular proteins involved in inflammation and apoptosis, Nat. Rev. Immunol., Volume 3 (2003), pp. 371-382","journal-title":"Nat. Rev. Immunol."},{"key":"key2025102316252688958_5","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/S0952-7915(00)00235-1","article-title":"Innate immune responses of epithelial cells following infection with bacterial pathogens","volume":"13","author":"Philpott, D.J.","year":"2001","unstructured":"[5] Philpott, D.J.; Girardin, S.E.; Sansonetti, P.J. Innate immune responses of epithelial cells following infection with bacterial pathogens, Curr. Opin. Immunol., Volume 13 (2001), pp. 410-416","journal-title":"Curr. Opin. Immunol."},{"key":"key2025102316252688958_6","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1093\/embo-reports\/kve155","article-title":"CARD4\/Nod1 mediates NF-kappaB and JNK activation by invasive Shigella flexneri","volume":"2","author":"Girardin, S.E.","year":"2001","unstructured":"[6] Girardin, S.E.; Tournebize, R.; Mavris, M.; Page, A.L.; Li, X.; Stark, G.R.; Bertin, J.; DiStefano, P.S.; Yaniv, M.; Sansonetti, P.J.; Philpott, D.J. CARD4\/Nod1 mediates NF-kappaB and JNK activation by invasive Shigella flexneri, EMBO Rep., Volume 2 (2001), pp. 736-742","journal-title":"EMBO Rep."},{"key":"key2025102316252688958_7","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1126\/science.1084677","article-title":"Nod1 detects a unique muropeptide from gram-negative bacterial peptidoglycan","volume":"300","author":"Girardin, S.E.","year":"2003","unstructured":"[7] Girardin, S.E.; Boneca, I.G.; Carneiro, L.A.; Antignac, A.; Jehanno, M.; Viala, J.; Tedin, K.; Taha, M.K.; Labigne, A.; Zathringer, U.; Coyle, A.J.; DiStefano, P.S.; Bertin, J.; Sansonetti, P.J.; Philpott, D.J. Nod1 detects a unique muropeptide from gram-negative bacterial peptidoglycan, Science, Volume 300 (2003), pp. 1584-1587","journal-title":"Science"},{"key":"key2025102316252688958_8","first-page":"18","article-title":"Peptidoglycan molecular requirements allowing detection by Nod1 and Nod2","volume":"18","author":"Girardin, S.E.","year":"2003","unstructured":"[8] Girardin, S.E.; Travassos, L.H.; Herve, M.; Blanot, D.; Boneca, I.G.; Philpott, D.J.; Sansonetti, P.J.; Mengin-Lecreulx, D. Peptidoglycan molecular requirements allowing detection by Nod1 and Nod2, J. Biol. Chem., Volume 18 (2003), p. 18","journal-title":"J. Biol. Chem."},{"key":"key2025102316252688958_9","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1038\/ni945","article-title":"An essential role for NOD1 in host recognition of bacterial peptidoglycan containing diaminopimelic acid","volume":"4","author":"Chamaillard, M.","year":"2003","unstructured":"[9] Chamaillard, M.; Hashimoto, M.; Horie, Y.; Masumoto, J.; Qiu, S.; Saab, L.; Ogura, Y.; Kawasaki, A.; Fukase, K.; Kusumoto, S.; Valvano, M.A.; Foster, S.J.; Mak, T.W.; Nunez, G.; Inohara, N. An essential role for NOD1 in host recognition of bacterial peptidoglycan containing diaminopimelic acid, Nat. Immunol., Volume 4 (2003), pp. 702-707","journal-title":"Nat. Immunol."},{"key":"key2025102316252688958_10","doi-asserted-by":"crossref","first-page":"41701","DOI":"10.1074\/jbc.M206473200","article-title":"Induction of Nod2 in myelomonocytic and intestinal epithelial cells via nuclear factor-kappa B activation","volume":"277","author":"Gutierrez, O.","year":"2002","unstructured":"[10] Gutierrez, O.; Pipaon, C.; Inohara, N.; Fontalba, A.; Ogura, Y.; Prosper, F.; Nunez, G.; Fernandez-Luna, J.L. Induction of Nod2 in myelomonocytic and intestinal epithelial cells via nuclear factor-kappa B activation, J. Biol. Chem., Volume 277 (2002), pp. 41701-41705","journal-title":"J. Biol. Chem."},{"key":"key2025102316252688958_11","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1053\/gast.2003.50157","article-title":"TNF-alpha and IFN-gamma regulate the expression of the NOD2 (CARD15) gene in human intestinal epithelial cells","volume":"124","author":"Rosenstiel, P.","year":"2003","unstructured":"[11] Rosenstiel, P.; Fantini, M.; Brautigam, K.; Kuhbacher, T.; Waetzig, G.H.; Seegert, D.; Schreiber, S. TNF-alpha and IFN-gamma regulate the expression of the NOD2 (CARD15) gene in human intestinal epithelial cells, Gastroenterology, Volume 124 (2003), pp. 1001-1009","journal-title":"Gastroenterology"},{"key":"key2025102316252688958_12","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/35079114","article-title":"A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease","volume":"411","author":"Ogura, Y.","year":"2001","unstructured":"[12] Ogura, Y.; Bonen, D.K.; Inohara, N.; Nicolae, D.L.; Chen, F.F.; Ramos, R.; Britton, H.; Moran, T.; Karaliuskas, R.; Duerr, R.H.; Achkar, J.P.; Brant, S.R.; Bayless, T.M.; Kirschner, B.S.; Hanauer, S.B.; Nunez, G.; Cho, J.H. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease, Nature, Volume 411 (2001), pp. 603-606","journal-title":"Nature"},{"key":"key2025102316252688958_13","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/35079107","article-title":"Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease","volume":"411","author":"Hugot, J.P.","year":"2001","unstructured":"[13] Hugot, J.P.; Chamaillard, M.; Zouali, H.; Lesage, S.; Cezard, J.P.; Belaiche, J.; Almer, S.; Tysk, C.; O'Morain, C.A.; Gassull, M.; Binder, V.; Finkel, Y.; Cortot, A.; Modigliani, R.; Laurent-Puig, P.; Gower-Rousseau, C.; Macry, J.; Colombel, J.F.; Sahbatou, M.; Thomas, G. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease, Nature, Volume 411 (2001), pp. 599-603","journal-title":"Nature"},{"key":"key2025102316252688958_14","doi-asserted-by":"crossref","first-page":"8869","DOI":"10.1074\/jbc.C200651200","article-title":"Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection","volume":"278","author":"Girardin, S.E.","year":"2003","unstructured":"[14] Girardin, S.E.; Boneca, I.G.; Viala, J.; Chamaillard, M.; Labigne, A.; Thomas, G.; Philpott, D.J.; Sansonetti, P.J. Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection, J. Biol. Chem., Volume 278 (2003), pp. 8869-8872","journal-title":"J. Biol. Chem."},{"key":"key2025102316252688958_15","doi-asserted-by":"crossref","first-page":"5509","DOI":"10.1074\/jbc.C200673200","article-title":"Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn's disease","volume":"278","author":"Inohara, N.","year":"2003","unstructured":"[15] Inohara, N.; Ogura, Y.; Fontalba, A.; Gutierrez, O.; Pons, F.; Crespo, J.; Fukase, K.; Inamura, S.; Kusumoto, S.; Hashimoto, M.; Foster, S.J.; Moran, A.P.; Fernandez-Luna, J.L.; Nunez, G. Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn's disease, J. Biol. Chem., Volume 278 (2003), pp. 5509-5512","journal-title":"J. Biol. Chem."}],"container-title":["Comptes Rendus. Biologies"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/comptes-rendus.academie-sciences.fr\/biologies\/item\/10.1016\/j.crvi.2004.02.010.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T14:28:21Z","timestamp":1761229701000},"score":1,"resource":{"primary":{"URL":"https:\/\/comptes-rendus.academie-sciences.fr\/biologies\/articles\/10.1016\/j.crvi.2004.02.010\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,5,25]]},"references-count":15,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2004]]}},"alternative-id":["10.1016\/j.crvi.2004.02.010"],"URL":"https:\/\/doi.org\/10.1016\/j.crvi.2004.02.010","relation":{},"ISSN":["1631-0691","1768-3238"],"issn-type":[{"value":"1631-0691","type":"print"},{"value":"1768-3238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,5,25]]}}}