The nodosome: Nod1 and Nod2 control bacterial infections and inflammation

Seminars in Immunopathology

Volumn 29, Issue 3, 2007, Pages 289-301

  Tattoli, Ivan ^a   Travassos, Leonardo H ^a   Carneiro, Leticia A ^a   Magalhaes, Joao G ^a   Girardin, Stephen E ^a  

^a UNIVERSITY OF TORONTO   (Canada)

Author keywords

Bacterial pathogenesis; Crohn's disease; Inflammation; Innate immunity; Nod like receptors; Nod1; Nod2

Indexed keywords

CASPASE RECRUITMENT DOMAIN PROTEIN 15; CASPASE RECRUITMENT DOMAIN PROTEIN 4; CYTOKINE; NITRIC OXIDE; NOD LIKE RECEPTOR; PEPTIDOGLYCAN; POLYPEPTIDE ANTIBIOTIC AGENT; RECEPTOR PROTEIN; TOLL LIKE RECEPTOR; UNCLASSIFIED DRUG;

ADAPTIVE IMMUNITY; ATOPY; BACTERIAL INFECTION; BACTERIUM DETECTION; BLAU SYNDROME; CELL MEMBRANE; CROHN DISEASE; CYTOSOL; GENE MUTATION; HUMAN; IMMUNE RESPONSE; INFLAMMATION; INFLAMMATORY DISEASE; INNATE IMMUNITY; MOLECULAR SENSOR; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; REVIEW; SARCOIDOSIS; SIGNAL TRANSDUCTION;

ANIMALS; BACTERIAL INFECTIONS; HUMANS; IMMUNE SYSTEM DISEASES; INFLAMMATION; MODELS, BIOLOGICAL; NOD1 SIGNALING ADAPTOR PROTEIN; NOD2 SIGNALING ADAPTOR PROTEIN; SIGNAL TRANSDUCTION;

EID: 34548688429     PISSN: 18632297     EISSN: 18632300     Source Type: Journal    
DOI: 10.1007/s00281-007-0083-2     Document Type: Review

References (134)

1. Abbott DW, Wilkins A, Asara JM, Cantley LC (2004) The Crohn's disease protein, NOD2, requires RIP2 in order to induce ubiquitinylation of a novel site on NEMO. Curr Biol 14:2217-2227
2. Akira S, Uematsu S, Takeuchi O (2006) Pathogen recognition and innate immunity. Cell 124:783-801
3. Aliprantis AO, Yang RB, Weiss DS, Godowski P, Zychlinsky A (2000) The apoptotic signaling pathway activated by Toll-like receptor-2. The EMBO J 19:3325-3336
4. Azevedo C, Sadanandom A, Kitagawa K, Freialdenhoven A, Shirasu K, Schulze-Lefert P (2002) The RAR1 interactor SGT1, an essential component of R gene-triggered disease resistance. Science 295:2073-2076
5. Barnich N, Hisamatsu T, Aguirre JE, Xavier R, Reinecker HC, Podolsky DK (2005) GRIM-19 interacts with nucleotide oligomerization domain 2 and serves as downstream effector of anti-bacterial function in intestinal epithelial cells. J Biol Chem 280:19021-19026
6. Barreiro-de Acosta M, Dominguez-Munoz JE, Nunez-Pardo de Vera MC, Lozano-Leon A, Lorenzo A, Pena S (2007) Relationship between clinical features of Crohn's disease and the risk of developing extraintestinal manifestations. Eur J Gastroenterol Hepatol 19:73-78
7. Becker ML, Rose CD (2005) Blau syndrome and related genetic disorders causing childhood arthritis. Curr Rheumatol Rep 7:427-433
8. Becker ML, Martin TM, Doyle TM, Rose CD (2007) Interstitial pneumonitis in Blau syndrome with documented mutation in CARD15. Arthritis Rheum 56:1292-1294
9. Berrebi D, Maudinas R, Hugot JP, Chamaillard M, Chareyre F, De Lagausie P, Yang C, Desreumaux P, Giovannini M, Cezard JP, Zouali H, Emilie D, Peuchmaur M (2003) Card15 gene overexpression in mononuclear and epithelial cells of the inflamed Crohn's disease colon. Gut 52:840-846
10. Bertin J, Nir WJ, Fischer CM, Tayber OV, Errada PR, Grant JR, Keilty JJ, Gosselin ML, Robison KE, Wong GH, Glucksmann MA, DiStefano PS (1999) Human CARD4 protein is a novel CED-4/Apaf-1 cell death family member that activates NF-kappaB. J Biol Chem 274:12955-12958
11. Blau EB (1985) Familial granulomatous arthritis, iritis, and rash. J Pediatr 107:689-693
12. Boneca IG (2005) The role of peptidoglycan in pathogenesis. Curr Opin Microbiol 8:46-53
13. Bonen DK, Cho JH (2003) The genetics of inflammatory bowel disease. Gastroenterology 124:521-536
14. Boughan PK, Argent RH, Body-Malapel M, Park J-H, Ewings KE, Bowie AG, Ong SJ, Cook SJ, Sorensen OE, Manzo BA, Inohara N, Klein NJ, Nunez G, Atherton JC, Bajaj-Elliott M (2006) Nucleotide-binding oligomerization domain-1 and epidermal growth factor receptor: critical regulators of beta-defensins during helicobacter pylori infection. J Biol Chem 281:11637-11648
15. Burns KA, Martinon F (2004) Inflammatory diseases: is ubiquitinated NEMO at the hub? Curr Biol 14:R1040-R1042
16. Chamaillard M, Hashimoto M, Horie Y, Masumoto J, Qiu S, Saab L, Ogura Y, Kawasaki A, Fukase K, Kusumoto S, Valvano MA, Foster SJ, Mak TW, Nunez G, Inohara N (2003) An essential role for NOD1 in host recognition of bacterial peptidoglycan containing diaminopimelic acid. Nat Immunol 4:702-707
17. Chamaillard M, Philpott D, Girardin SE, Zouali H, Lesage S, Chareyre F, Bui TH, Giovannini M, Zaehringer U, Penard-Lacronique V, Sansonetti PJ, Hugot JP, Thomas G (2003) Gene-environment interaction modulated by allelic heterogeneity in inflammatory diseases. Proc Natl Acad Sci U S A 100:3455-3460
18. Chan CC, Smith JA, Shen DF, Ursea R, LeHoang P, Grossniklaus HE (2004) Helicobacter pylori (H. pylori) molecular signature in conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma. Histol Histopathol 19:1219-1226
19. Chen CM, Gong Y, Zhang M, Chen JJ (2004) Reciprocal cross-talk between Nod2 and TAK1 signaling pathways. J Biol Chem 279:25876-25882
20. D'Inca R, Annese V, Di Leo V, Latiano A, Quaino V, Abazia C, Vettorato MG, Sturniolo GC (2006) Increased intestinal permeability and NOD2 variants in familial and sporadic Crohn's disease. Aliment Pharmacol Ther 23:1455-1461
21. da Silva Correia J, Miranda Y, Austin-Brown N, Hsu J, Mathison J, Xiang R, Zhou H, Li Q, Han J, Ulevitch RJ (2006) Nod1-dependent control of tumor growth. Proc Natl Acad Sci U S A 103:1840-1845
22. da Silva Correia J, Miranda Y, Leonard N, Hsu J, Ulevitch RJ (2006) Regulation of Nod1-mediated signaling pathways. Cell Death Differ 14(4):830-839
23. da Silva Correia J, Miranda Y, Leonard N, Ulevitch R (2007) SGT1 is essential for Nod1 activation. Proc Natl Acad Sci U S A 104:6764-6769
24. da Silva Correia J, Miranda Y, Leonard N, Ulevitch RJ (2007) The subunit CSN6 of the COP9 signalosome is cleaved during apoptosis. J Biol Chem 282(17):12557-12565
25. David Sterka DMRIM Jr (2006) Functional expression of NOD2, a novel pattern recognition receptor for bacterial motifs, in primary murine astrocytes. Glia 53:322-330
26. Dufner A, Mak TW (2006) CARD tricks: controlling the interactions of CARD6 with RICK and microtubules. Cell cycle (Georgetown). Tex 5:797-800
27. Dziarski R, Gupta D (2005) Staphylococcus aureus peptidoglycan is a toll-like receptor 2 activator: a reevaluation. Infect Immun 73:5212-5216
28. Eckmann L, Karin M (2005) NOD2 and Crohn's disease: loss or gain of function? Immunity 22:661-667
29. Economou M, Trikalinos TA, Loizou KT, Tsianos EV, Ioannidis JP (2004) Differential effects of NOD2 variants on Crohn's disease risk and phenotype in diverse populations: a metaanalysis. Am J Gastroenterol 99:2393-2404
30. Eder W, Klimecki W, Yu L, von Mutius E, Riedler J, Braun-Fahrlander C, Nowak D, Holst O, Martinez FD (2006) Association between exposure to farming, allergies and genetic variation in CARD4/NOD1. Allergy 61:1117-1124
31. Ferwerda G, Girardin SE, Kullberg B-J, Le Bourhis L, de Jong DJ, Langenberg DML, van Crevel R, Adema GJ, Ottenhoff THM, Van der Meer JWM, Netea MG (2005) NOD2 and Toll-like receptors are nonredundant recognition systems of mycobacterium tuberculosis. PLoS Pathogens 1:e34
32. Fritz JH, Ferrero RL, Philpott DJ, Girardin SE (2006) Nod-like proteins in immunity, inflammation and disease. Nat Immunol 7:1250-1257
33. Fritz JH, Le Bourhis L, Sellge G, Magalhaes JG, Fsihi H, Kufer TA, Collins C, Viala J, Ferrero RL, Girardin SE, Philpott DJ (2007) Nod1-mediated innate immune recognition of peptidoglycan contributes to the onset of adaptive immunity. Immunity 26(4):445-459
34. Girardin SE, Tournebize R, Mavris M, Page AL, Li X, Stark GR, Bertin J, DiStefano PS, Yaniv M, Sansonetti PJ, Philpott DJ (2001) CARD4/Nod1 mediates NF-kappaB and JNK activation by invasive Shigella flexneri. EMBO Reports 2:736-742
35. Girardin SE, Sansonetti PJ, Philpott DJ (2002) Intracellular vs extracellular recognition of pathogens-common concepts in mammals and flies. Trends Microbiol 10:193-199
36. Girardin SE, Boneca IG, Carneiro LAM, Antignac A, Jehanno M, Viala J, Tedin K, Taha M-K, Labigne A, Zathringer U, Coyle AJ, DiStefano PS, Bertin J, Sansonetti PJ, Philpott DJ (2003) Nod1 Detects a Unique Muropeptide from Gram-Negative Bacterial Peptidoglycan. Science 300:1584-1587
37. Girardin SE, Boneca IG, Viala J, Chamaillard M, Labigne A, Thomas G, Philpott DJ, Sansonetti PJ (2003) Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection. J Biol Chem 278:8869-8872
38. Girardin SE, Jehanno M, Mengin-Lecreulx D, Sansonetti PJ, Alzari PM, Philpott DJ (2005) Identification of the critical residues involved in peptidoglycan detection by Nod1. J Biol Chem 280:38648-38656
39. Guo QS, Xia B, Jiang Y, Qu Y, Li J (2004) NOD2 3020insC frameshift mutation is not associated with inflammatory bowel disease in Chinese patients of Han nationality. World J Gastroenterol 10:1069-1071
40. Hampe J, Cuthbert A, Croucher PJ, Mirza MM, Mascheretti S, Fisher S, Frenzel H, King K, Hasselmeyer A, MacPherson AJ, Bridger S, van Deventer S, Forbes A, Nikolaus S, Lennard-Jones JE, Foelsch UR, Krawczak M, Lewis C, Schreiber S, Mathew CG (2001) Association between insertion mutation in NOD2 gene and Crohn's disease in German and British populations. Lancet 357:1925-1928
41. Hisamatsu T, Suzuki M, Reinecker HC, Nadeau WJ, McCormick BA, Podolsky DK (2003) CARD15/NOD2 functions as an antibacterial factor in human intestinal epithelial cells. Gastroenterology 124:993-1000
42. Hofmann K, Bucher P, Tschopp J (1997) The CARD domain: a new apoptotic signalling motif. Trends Biochem Sci 22:155-156
43. Hsu Y-MS, Zhang Y, You Y, Wang D, Li H, Duramad O, Qin X-F, Dong C, Lin X (2007) The adaptor protein CARD9 is required for innate immune responses to intracellular pathogens. Nat Immunol 8:198-205
44. Hugot JP, Chamaillard M, Zouali H, Lesage S, Cezard JP, Belaiche J, Almer S, Tysk C, O'Morain CA, Gassull M, Binder V, Finkel Y, Cortot A, Modigliani R, Laurent-Puig P, Gower-Rousseau C, Macry J, Colombel JF, Sahbatou M, Thomas G (2001) Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 411:599-603
45. Hysi P, Kabesch M, Moffatt MF, Schedel M, Carr D, Zhang Y, Boardman B, von Mutius E, Weiland SK, Leupold W, Fritzsch C, Klopp N, Musk AW, James A, Nunez G, Inohara N, Cookson WO (2005) NOD1 variation, immunoglobulin E and asthma. Hum Mol Genet 14:935-941
46. Inohara N, Koseki T, del Peso L, Hu Y, Yee C, Chen S, Carrio R, Merino J, Liu D, Ni J, Nunez G (1999) Nod1, an Apaf-1-like activator of caspase-9 and nuclear factor-kappaB. J Biol Chem 274:14560-14567
47. Inohara N, Koseki T, Lin J, del Peso L, Lucas PC, Chen FF, Ogura Y, Nunez G (2000) An induced proximity model for NF-kappa B activation in the Nod1/RICK and RIP signaling pathways. J Biol Chem 275:27823-27831
48. Inohara N, Ogura Y, Nunez G (2002) Nods: a family of cytosolic proteins that regulate the host response to pathogens. Curr Opin Microbiol 5:76-80
49. Inohara N, Ogura Y, Fontalba A, Gutierrez O, Pons F, Crespo J, Fukase K, Inamura S, Kusumoto S, Hashimoto M, Foster SJ, Moran AP, Fernandez-Luna JL, Nunez G (2003) Host Recognition of Bacterial Muramyl Dipeptide Mediated through NOD2. Implications for crohn's disease. J Biol Chem 278:5509-5512
50. Inoue N, Tamura K, Kinouchi Y, Fukuda Y, Takahashi S, Ogura Y, Inohara N, Nunez G, Kishi Y, Koike Y, Shimosegawa T, Shimoyama T, Hibi T (2002) Lack of common NOD2 variants in Japanese patients with Crohn's disease. Gastroenterology 123:86-91
51. Ismair MG, Vavricka SR, Kullak-Ublick GA, Fried M, Mengin-Lecreulx D, Girardin SE (2006) hPepT1 selectively transports muramyl dieptide but not Nod1-activating muramyl peptides. Can J Physiol Pharmacol 84:1313-1319
52. Jörg H (2005) Fritz Stephen EGCFCWDM-LMCJ-MCDana JPMA-C Synergistic stimulation of human monocytes and dendritic cells by Toll-like receptor 4 and NOD1- and NOD2-activating agonists. Eur J Immunol 35:2459-2470
53. Kanazawa N, Matsushima S, Kambe N, Tachibana T, Nagai S, Miyachi Y (2004) Presence of a sporadic case of systemic granulomatosis syndrome with a CARD15 mutation. J Invest Dermatol 122:851-852
54. Kanazawa N, Okafuji I, Kambe N, Nishikomori R, Nakata-Hizume M, Nagai S, Fuji A, Yuasa T, Manki A, Sakurai Y, Nakajima M, Kobayashi H, Fujiwara I, Tsutsumi H, Utani A, Nishigori C, Heike T, Nakahata T, Miyachi Y (2005) Early-onset sarcoidosis and CARD15 mutations with constitutive nuclear factor-kappaB activation: common genetic etiology with Blau syndrome. Blood 105:1195-1197
55. Kim JG, Lee SJ, Kagnoff MF (2004) Nod1 is an essential signal transducer in intestinal epithelial cells infected with bacteria that avoid recognition by Toll-like receptors. Infect Immun 72:1487-1495
56. Kitagawa K, Skowyra D, Elledge SJ, Harper JW, Hieter P (1999) SGT1 encodes an essential component of the yeast kinetochore assembly pathway and a novel subunit of the SCF ubiquitin ligase complex. Mol Cell 4:21-33
57. Kobayashi KS, Chamaillard M, Ogura Y, Henegariu O, Inohara N, Nunez G, Flavell RA (2005) Nod2-Dependent regulation of innate and adaptive immunity in the intestinal tract. Science 307:731-734
58. Kufer TA, Kremmer E, Banks DJ, Philpott DJ (2006) Role for erbin in bacterial activation of Nod2. Infection and immunity 74:3115-3124
59. Lakatos PL, Szalay F, Tulassay Z, Molnar T, Kovacs A, Gasztonyi B, Papp J, Lakatos L (2005) Clinical presentation of Crohn's disease. association between familial disease, smoking, disease phenotype, extraintestinal manifestations and need for surgery. Hepatogastroenterology 52:817-822
60. Lakatos PL, Hitre E, Szalay F, Zinober K, Fuszek P, Lakatos L, Fischer S, Osztovits J, Gemela O, Veres G, Papp J, Ferenci P (2007) Common NOD2/CARD15 variants are not associated with susceptibility or the clinicopathologic characteristics of sporadic colorectal cancer in Hungarian patients. BMC Cancer 7:54
61. Lala S, Ogura Y, Osborne C, Hor SY, Bromfield A, Davies S, Ogunbiyi O, Nunez G, Keshav S (2003) Crohn's disease and the NOD2 gene: a role for paneth cells. Gastroenterology 125:47-57
62. Lazarus R, Vercelli D, Palmer LJ, Klimecki WJ, Silverman EK, Richter B, Riva A, Ramoni M, Martinez FD, Weiss ST, Kwiatkowski DJ (2002) Single nucleotide polymorphisms in innate immunity genes: abundant variation and potential role in complex human disease. Immunol Rev 190:9-25
63. Lecine P, Esmiol S, Metais J-Y, Nicoletti C, Nourry C, McDonald C, Nunez G, Hugot J-P, Borg J-P, Ollendorff V (2007) The NOD2-RICK complex signals from the plasma membrane. J Biol Chem 282(20):15197-15207
64. Lesage S, Zouali H, Cezard JP, Colombel JF, Belaiche J, Almer S, Tysk C, O'Morain C, Gassull M, Binder V, Finkel Y, Modigliani R, Gower-Rousseau C, Macry J, Merlin F, Chamaillard M, Jannot AS, Thomas G, Hugot JP (2002) CARD15/NOD2 mutational analysis and genotype-phenotype correlation in 612 patients with inflammatory bowel disease. Am J Hum Genet 70:845-857
65. Li J, Moran T, Swanson E, Julian C, Harris J, Bonen DK, Hedl M, Nicolae DL, Abraham C, Cho JH (2004) Regulation of IL-8 and IL-1{beta} expression in Crohn's disease associated NOD2/CARD15 mutations. Hum Mol Genet 13:1715-1725
66. Li L, Bin LH, Li F, Liu Y, Chen D, Zhai Z, Shu HB (2005) TRIP6 is a RIP2-associated common signaling component of multiple NF-kappaB activation pathways. J Cell Sci 118:555-563
67. Lyapina S, Cope G, Shevchenko A, Serino G, Tsuge T, Zhou C, Wolf DA, Wei N, Shevchenko A, Deshaies RJ (2001) Promotion of NEDD-CUL1 conjugate cleavage by COP9 signalosome. Science 292:1382-1385
68. Magalhaes JG (2005) Murine Nod1 but not its human orthologue mediates innate immune detection of tracheal cytotoxin. EMBO Rep 6:1201-1207
69. Mahida YR, Rolfe VE (2004) Host-bacterial interactions in inflammatory bowel disease. Clin Sci (Lond) 107:331-341
70. Manguso F, Sanges M, Staiano T, Gargiulo S, Nastro P, Gargano D, Somma P, Mansueto G, Peluso R, Scarpa R, D'Armiento FP, Astarita C, Ayala F, Renda A, Mazzacca G, D'Arienzo A (2004) Cigarette smoking and appendectomy are risk factors for extraintestinal manifestations in ulcerative colitis. Am J Gastroenterol 99:327-334
71. Marks DJB, Harbord MWN, MacAllister R, Rahman FZ, Young J, Al-Lazikani B, Lees W, Novelli M, Bloom S, Segal AW (2006) Defective acute inflammation in Crohn's disease: a clinical investigation. The Lancet 367:668-678
72. Marriott I, Rati DM, McCall SH, Tranguch SL (2005) Induction of Nod1 and Nod2 intracellular pattern recognition receptors in murine osteoblasts following bacterial challenge. Infect Immun 73:2967-2973
73. Masumoto J, Yang K, Varambally S, Hasegawa M, Tomlins SA, Qiu S, Fujimoto Y, Kawasaki A, Foster SJ, Horie Y, Mak TW, Nunez G, Chinnaiyan AM, Fukase K, Inohara N (2006) Nod1 acts as an intracellular receptor to stimulate chemokine production and neutrophil recruitment in vivo. J Exp Med 203:203-213
74. Mayor A, Martinon F, De Smedt T, Petrilli V, Tschopp J (2007) A crucial function of SGT1 and HSP90 in inflammasome activity links mammalian and plant innate immune responses. Nat Immunol 8:497-503
75. McDonald C, Chen FF, Ollendorff V, Ogura Y, Marchetto S, Lecine P, Borg JP, Nunez G (2005) A role for Erbin in the regulation of Nod2-dependent NF-kappaB signaling. J Biol Chem 280:40301-40309
76. McGovern DP, Hysi P, Ahmad T, van Heel DA, Moffatt MF, Carey A, Cookson WO, Jewell DP (2005) Association between a complex insertion/deletion polymorphism in NOD1 (CARD4) and susceptibility to inflammatory bowel disease. Hum Mol Genet 14:1245-1250
77. Medzhitov R, Preston-Hurlburt P, Janeway CA, Jr. (1997) A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388:394-397
78. Meylan E, Tschopp J, Karin M (2006) Intracellular pattern recognition receptors in the host response. Nature 442:39-44
79. Miceli-Richard C, Lesage S, Rybojad M, Prieur AM, Manouvrier-Hanu S, Hafner R, Chamaillard M, Zouali H, Thomas G, Hugot JP (2001) CARD15 mutations in Blau syndrome. Nat Genet 29:19-20
80. Mihai G (2004) Netea Bart JKDirk JdJBFTSTon HJNJoost PHDJos WMVdM NOD2 mediates anti-inflammatory signals induced by TLR2 ligands: implications for Crohn's disease. Eur J Immunol 34:2052-2059
81. Milman N, Nielsen OH, Hviid TV, Fenger K (2007) CARD15 single nucleotide polymorphisms 8, 12 and 13 are not increased in ethnic Danes with sarcoidosis. Respiration 74:76-79
82. Munkholm P (2003) Review article: the incidence and prevalence of colorectal cancer in inflammatory bowel disease. Aliment Pharmacol Ther 18(Suppl 2):1-5
83. Netea MG, Azam T, Ferwerda G, Girardin SE, Walsh M, Park prevalenceJ-S, Abraham E, Kim J-M, Yoon D-Y, Dinarello CA, Kim S-H (2005) IL-32 synergizes with nucleotide oligomerization domain (NOD) 1 and NOD2 ligands for IL-1{beta} and IL-6 production through a caspase 1-dependent mechanism. PNAS 102:16309-16314
84. Netea MG, Ferwerda G, de Jong DJ, Girardin SE, Kullberg BJ, van der Meer JW (2005) NOD2 3020insC mutation and the pathogenesis of Crohn's disease: impaired IL-1beta production points to a loss-of-function phenotype. Neth J Med 63:305-308
85. Netea MG, Ferwerda G, de Jong DJ, Jansen T, Jacobs L, Kramer M, Naber THJ, Drenth JPH, Girardin SE, Jan Kullberg B, Adema GJ, Van der Meer JWM (2005) Nucleotide-binding oligomerization domain-2 modulates specific TLR pathways for the induction of cytokine release. J Immunol 174:6518-6523
86. Netea MG, Ferwerda G, de Jong DJ, Werts C, Boneca IG, Jehanno M, Van Der Meer JWM, Mengin-Lecreulx D, Sansonetti PJ, Philpott DJ, Dharancy S, Girardin SE (2005) The frameshift mutation in Nod2 results in unresponsiveness not only to Nod2- but also Nod1-activating peptidoglycan agonists. J Biol Chem 280:35859-35867
87. O'Riordan M, Yi CH, Gonzales R, Lee KD, Portnoy DA (2002) Innate recognition of bacteria by a macrophage cytosolic surveillance pathway. Proc Natl Acad Sci U S A 99:13861-13866
88. Ogura Y, Bonen DK, Inohara N, Nicolae DL, Chen FF, Ramos R, Britton H, Moran T, Karaliuskas R, Duerr RH, Achkar JP, Brant SR, Bayless TM, Kirschner BS, Hanauer SB, Nunez G, Cho JH (2001) A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature 411:603-606
89. Ogura Y, Lala S, Xin W, Smith E, Dowds TA, Chen FF, Zimmermann E, Tretiakova M, Cho JH, Hart J, Greenson JK, Keshav S, Nunez G (2003) Expression of NOD2 in Paneth cells: a possible link to Crohn's ileitis. Gut 52:1591-1597
90. Opitz B, Puschel A, Schmeck B, Hocke AC, Rosseau S, Hammerschmidt S, Schumann RR, Suttorp N, Hippenstiel S (2004) Nucleotide-binding Oligomerization Domain Proteins Are Innate Immune Receptors for Internalized Streptococcus pneumoniae. J Biol Chem 279:36426-36432
91. Opitz B, Forster S, Hocke AC, Maass M, Schmeck B, Hippenstiel S, Suttorp N, Krull M (2005) Nod1-mediated endothelial cell activation by chlamydophila pneumoniae. Circ Res 96:319-326
92. Opitz B, Puschel A, Beermann W, Hocke AC, Forster S, Schmeck B, van Laak V, Chakraborty T, Suttorp N, Hippenstiel S (2006) Listeria monocytogenes activated p38 MAPK and induced IL-8 secretion in a nucleotide-binding oligomerization domain 1-dependent manner in endothelial cells. J Immunol 176:484-490
93. Otte JM, Rosenberg IM, Podolsky DK (2003) Intestinal myofibroblasts in innate immune responses of the intestine. Gastroenterology 124:1866-1878
94. Papaconstantinou I, Theodoropoulos G, Gazouli M, Panoussopoulos D, Mantzaris GJ, Felekouras E, Bramis J (2005) Association between mutations in the CARD15/NOD2 gene and colorectal cancer in a Greek population. Int J Cancer 114:433-435
95. Park J-H, Kim Y-G, McDonald C, Kanneganti T-D, Hasegawa M, Body-Malapel M, Inohara N, Nunez G (2007) RICK/RIP2 Mediates innate immune responses induced through Nod1 and Nod2 but Not TLRs. J Immunol 178:2380-2386
96. Philpott DJ, Yamaoka S, Israel A, Sansonetti PJ (2000) Invasive Shigella flexneri activates NF-[kappa]B through a lipopolysaccharide-dependent innate intracellular response and leads to IL-8 expression in epithelial cells. J Immunol 165:903-914
97. Roberts RL, Gearry RB, Allington MD, Morrin HR, Robinson BA, Frizelle FA (2006) Caspase recruitment domain-containing protein 15 mutations in patients with colorectal cancer. Cancer Res 66:2532-2535
98. Rose CD, Doyle TM, McIlvain-Simpson G, Coffman JE, Rosenbaum JT, Davey MP, Martin TM (2005) Blau syndrome mutation of CARD15/NOD2 in sporadic early onset granulomatous arthritis. J Rheumatol 32:373-375
99. Rosenstiel P, Hellmig S, Hampe J, Ott S, Till A, Fischbach W, Sahly H, Lucius R, Folsch UR, Philpott D, Schreiber S (2006) Influence of polymorphisms in the NOD1/CARD4 and NOD2/CARD15 genes on the clinical outcome of Helicobacter pylori infection. Cell Microbiol 8:1188-1198
100. Schurmann M, Valentonyte R, Hampe J, Muller-Quernheim J, Schwinger E, Schreiber S (2003) CARD15 gene mutations in sarcoidosis. Eur Respir J 22:748-754
101. Shaoul R, Eliakim R, Tamir A, Karban A (2006) Ileal lymphonodular hyperplasia is not associated with NOD2/CARD15 mutations. J Pediatr Gastroenterol Nutr 43:30-34
102. Stehlik C, Hayashi H, Pio F, Godzik A, Reed JC (2003) CARD6 is a modulator of NF-kappa B activation by Nod1- and Cardiak-mediated pathways. J Biol Chem 278:31941-31949
103. Tada H, Aiba S, Shibata K-I, Ohteki T, Takada H (2005) Synergistic effect of Nod1 and Nod2 agonists with toll-like receptor agonists on human dendritic cells to generate interleukin-12 and T helper Type 1 cells. Infect Immun 73:7967-7976
104. Tanabe T, Ishige I, Suzuki Y, Aita Y, Furukawa A, Ishige Y, Uchida K, Suzuki T, Takemura T, Ikushima S, Oritsu M, Yokoyama T, Fujimoto Y, Fukase K, Inohara N, Nunez G, Eishi Y (2006) Sarcoidosis and NOD1 variation with impaired recognition of intracellular Propionibacterium acnes. Biochim Biophys Acta 1762:794-801
105. Totemeyer S, Sheppard M, Lloyd A, Roper D, Dowson C, Underhill D, Murray P, Maskell D, Bryant C (2006) IFN-{gamma} Enhances Production of Nitric Oxide from Macrophages via a Mechanism That Depends on Nucleotide Oligomerization Domain-2. J Immunol 176:4804-4810
106. Traub S, Kubasch N, Morath S, Kresse M, Hartung T, Schmidt RR, Hermann C (2004) Structural requirements of synthetic muropeptides to synergize with lipopolysaccharide in cytokine induction. J Biol Chem 279:8694-8700
107. Travassos LH, Girardin SE, Philpott DJ, Blanot D, Nahori MA, Werts C, Boneca IG (2004) Toll-like receptor 2-dependent bacterial sensing does not occur via peptidoglycan recognition. EMBO Reports 5:1000-1006
108. Travassos LH, Carneiro LAM, Girardin SE, Boneca IG, Lemos R, Bozza MT, Domingues RCP, Coyle AJ, Bertin J, Philpott DJ, Plotkowski MC (2005) Nod1 Participates in the Innate Immune Response to Pseudomonas aeruginosa. J Biol Chem 280:36714-36718
109. Tremelling M, Hancock L, Bredin F, Sharpstone D, Bingham SA, Parkes M (2006) Complex insertion/deletion polymorphism in NOD1 (CARD4) is not associated with inflammatory bowel disease susceptibility in East Anglia panel. Inflamm Bowel Dis 12:967-971
110. Tuupanen S, Alhopuro P, Mecklin JP, Jarvinen H, Aaltonen LA (2007) No evidence for association of NOD2 R702W and G908R with colorectal cancer. Int J Cancer
111. Uehara A, Yang S, Fujimoto Y, Fukase K, Kusumoto S, Shibata K, Sugawara S, Takada H (2005) Muramyldipeptide and diaminopimelic acid-containing desmuramylpeptides in combination with chemically synthesized Toll-like receptor agonists synergistically induced production of interleukin-8 in a NOD2- and NOD1-dependent manner, respectively, in human monocytic cells in culture. Cell Microbiol 7:53-61
112. Uehara A, Fujimoto Y, Kawasaki A, Kusumoto S, Fukase K, Takada H (2006) Meso-diaminopimelic acid and meso-lanthionine, amino acids specific to bacterial peptidoglycans, activate human epithelial cells through NOD1. J Immunol 177:1796-1804
113. Uehara A, Fujimoto Y, Fukase K, Takada H (2007) Various human epithelial cells express functional Toll-like receptors, NOD1 and NOD2 to produce anti-microbial peptides, but not proinflammatory cytokines. Mol Immunol 44:3100-3111
114. van Duist MM, Albrecht M, Podswiadek M, Giachino D, Lengauer T, Punzi L, De Marchi M (2005) A new CARD15 mutation in Blau syndrome. Eur J Hum Genet 13:742-747
115. van Heel DA, Ghosh S, Butler M, Hunt KA, Lundberg AM, Ahmad T, McGovern DP, Onnie C, Negoro K, Goldthorpe S, Foxwell BM, Mathew CG, Forbes A, Jewell DP, Playford RJ (2005) Muramyl dipeptide and toll-like receptor sensitivity in NOD2-associated Crohn's disease. Lancet 365:1794-1796
116. van Heel DA, Ghosh S, Hunt KA, Mathew CG, Forbes A, Jewell DP, Playford RJ (2005) Synergy between TLR9 and NOD2 innate immune responses is lost in genetic Crohn's disease. Gut 54:1553-1557
117. Van Limbergen J, Russell RK, Nimmo ER, Torkvist L, Lees CW, Drummond HE, Smith L, Anderson NH, Gillett PM, McGrogan P, Hassan K, Weaver LT, Bisset WM, Mahdi G, Arnott ID, Sjoqvist U, Lordal M, Farrington SM, Dunlop MG, Wilson DC, Satsangi J (2007) Contribution of the NOD1/CARD4 insertion/deletion polymorphism +32656 to inflammatory bowel disease in Northern Europe. Inflamm Bowel Dis 13(7):882-889
118. Vavricka SR, Musch MW, Chang JE, Nakagawa Y, Phanvijhitsiri K, Waypa TS, Merlin D, Schneewind O, Chang EB (2004) hPepT1 transports muramyl dipeptide, activating NF-kappaB and stimulating IL-8 secretion in human colonic Caco2/bbe cells. Gastroenterology 127:1401-1409
119. Viala J, Chaput C, Boneca IG, Cardona A, Girardin SE, Moran AP, Athman R, Memet S, Huerre MR, Coyle AJ, DiStefano PS, Sansonetti PJ, Labigne A, Bertin J, Philpott DJ, Ferrero RL (2004) Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island. Nat Immunol 5:1166-1174
120. Voss E, Wehkamp J, Wehkamp K, Stange EF, Schroder JM, Harder J (2006) NOD2/CARD15 mediates induction of the antimicrobial peptide human beta-defensin-2. J Biol Chem 281:2005-2011
121. Watanabe T, Kitani A, Murray PJ, Strober W (2004) NOD2 is a negative regulator of Toll-like receptor 2-mediated T helper type 1 responses. Nat Immunol 5:800-808
122. Watanabe T, Kitani A, Murray PJ, Wakatsuki Y, Fuss IJ, Strober W (2006) Nucleotide binding oligomerization domain 2 deficiency leads to dysregulated TLR2 signaling and induction of antigen-specific colitis. Immunity 25:473-485
123. Wehkamp J, Harder J, Weichenthal M, Schwab M, Schaffeler E, Schlee M, Herrlinger KR, Stallmach A, Noack F, Fritz P, Schroder JM, Bevins CL, Fellermann K, Stange EF (2004) NOD2 (CARD15) mutations in Crohn's disease are associated with diminished mucosal alpha-defensin expression. Gut 53:1658-1664
124. Weidinger S, Klopp N, Rummler L, Wagenpfeil S, Novak N, Baurecht HJ, Groer W, Darsow U, Heinrich J, Gauger A, Schafer T, Jakob T, Behrendt H, Wichmann HE, Ring J, Illig T (2005) Association of NOD1 polymorphisms with atopic eczema and related phenotypes. J Allergy Clin Immunol 116:177-184
125. Welter-Stahl L, Ojcius DM, Viala J, Girardin S, Liu W, Delarbre C, Philpott D, Kelly KA, Darville T (2006) Stimulation of the cytosolic receptor for peptidoglycan, Nod1, by infection with Chlamydia trachomatis or Chlamydia muridarum. Cell Microbiol 8:1047-1057
126. Werts C, Girardin SE, Philpott DJ (2006) TIR, CARD and PYRIN: three domains for an antimicrobial triad. Cell Death Differ 13:798-815
127. Wolfert MA, Murray TF, Boons G-J, Moore JN (2002) The origin of the synergistic effect of muramyl dipeptide with endotoxin and peptidoglycan. J Biol Chem 277:39179-39186
128. Wright SD, Ramos RA, Tobias PS, Ulevitch RJ, Mathison JC (1990) CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science 249:1431-1433
129. Yamazaki K, Takazoe M, Tanaka T, Kazumori T, Nakamura Y (2002) Absence of mutation in the NOD2/CARD15 gene among 483 Japanese patients with Crohn's disease. J Hum Genet 47:469-472
130. Yang S, Tamai R, Akashi S, Takeuchi O, Akira S, Sugawara S, Takada H (2001) Synergistic effect of muramyldipeptide with lipopolysaccharide or lipoteichoic acid to induce inflammatory cytokines in human monocytic cells in culture. Infect Immun 69:2045-2053
131. Yoo NJ, Park WS, Kim SY, Reed JC, Son SG, Lee JY, Lee SH (2002) Nod1, a CARD protein, enhances pro-interleukin-1beta processing through the interaction with pro-caspase-1. Biochem Biophys Res Commun 299:652-658
132. Zaahl MG, Winter T, Warnich L, Kotze MJ (2005) Analysis of the three common mutations in the CARD15 gene (R702W, G908R and 1007fs) in South African colored patients with inflammatory bowel disease. Mol Cell Probes 19:278-281
133. Zouali H, Lesage S, Merlin F, Cezard JP, Colombel JF, Belaiche J, Almer S, Tysk C, O'Morain C, Gassull M, Christensen S, Finkel Y, Modigliani R, Gower-Rousseau C, Macry J, Chamaillard M, Thomas G, Hugot JP (2003) CARD4/NOD1 is not involved in inflammatory bowel disease. Gut 52:71-74
134. Zouiten-Mekki L, Zaouali H, Boubaker J, Karoui S, Fekih M, Matri S, Hamzaoui S, Filali A, Chaabouni H, Hugot JP (2005) CARD15/NOD2 in a Tunisian population with Crohn's disease. Dig Dis Sci 50:130-135