NOD2, an intracellular innate immune sensor involved in host defense and Crohn's disease

Mucosal Immunology

Volumn 4, Issue 5, 2011, Pages 484-495

  Strober, W ^a   Watanabe, T ^b  

^a NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

^b KYOTO UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

CASPASE RECRUITMENT DOMAIN PROTEIN 15; INTERFERON; PROTEIN SERINE KINASE; RICK PROTEIN; TOLL LIKE RECEPTOR; UNCLASSIFIED DRUG;

AUTOIMMUNITY; AUTOPHAGY; CARD15 GENE; CROHN DISEASE; DISEASE ASSOCIATION; GENE; GENETIC ASSOCIATION; GRAFT VERSUS HOST REACTION; HOST RESISTANCE; HUMAN; INNATE IMMUNITY; MOLECULAR INTERACTION; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN FUNCTION; PROTEIN POLYMORPHISM; PROTEIN STRUCTURE; REVIEW; SIGNAL TRANSDUCTION;

EID: 84860389274     PISSN: 19330219     EISSN: 19353456     Source Type: Journal    
DOI: 10.1038/mi.2011.29     Document Type: Review

References (77)

1. Strober, W., Murray, P. J., Kitani, A. & Watanabe, T. Signalling pathways and molecular interactions of NOD1 and NOD2. Nat. Rev. Immunol. 6, 9-20 (2006). (Pubitemid 43279749)
2. Inohara, Chamaillard, McDonald, C. & Nunez, G. NOD-LRR proteins: role in host-microbial interactions and inflammatory disease. Annu. Rev. Biochem. 74, 355-383 (2005). (Pubitemid 40995511)
3. Cho, J. H. The genetics and immunopathogenesis of inflammatory bowel disease. Nat. Rev. Immunol. 8, 458-466 (2008). (Pubitemid 351733422)
4. Holler, E. et al. Both donor and recipient NOD2/CARD15 mutations associate with transplant-related mortality and GvHD following allogeneic stem cell transplantation. Blood 104, 889-894 (2004). (Pubitemid 38970589)
5. Henckaerts, L. & Vermeire, S. NOD2/CARD15 disease associations other than Crohn's disease. Inflamm. Bowel Dis. 13, 235-241 (2007). (Pubitemid 46806233)
6. Kobayashi, K. S. et al. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 307, 731-734 (2005). (Pubitemid 40194644)
7. Park, J. H. et al. RICK/RIP2 mediates innate immune responses induced through Nod1 and Nod2 but not TLRs. J. Immunol. 178, 2380-2386 (2007).
8. Hasegawa, M. et al. A critical role of RICK/RIP2 polyubiquitination in Nod-induced NF-kappaB activation. EMBO J. 27, 373-383 (2008). (Pubitemid 351161652)
9. Abbott, D. W., Wilkins, A., Asara, J. M. & Cantley, L. C. The Crohn's disease protein, NOD2, requires RIP2 in order to induce ubiquitinylation of a novel site on NEMO. Curr. Biol. 14, 2217-2227 (2004). (Pubitemid 40033358)
10. Abbott, D. W., Yang, Y., Hutti, J. E., Madhavarapu, S., Kelliher, M. A. & Cantley, L. C. Coordinated regulation of Toll-like receptor and NOD2 signaling by K63-linked polyubiquitin chains. Mol. Cell. Biol. 27, 6012-6025 (2007). (Pubitemid 47326691)
11. Bertrand, M. J., Doiron, K., Labbe, K., Korneluk, R. G., Barker, P. A. & Saleh, M. Cellular inhibitors of apoptosis cIAP1 and cIAP2 are required for innate immunity signaling by the pattern recognition receptors NOD1 and NOD2. Immunity 30, 789-801 (2009).
12. Kim, J. Y., Omori, E., Matsumoto, K., Nunez, G. & Ninomiya-Tsuji, J. T A K 1 is a central mediator of NOD2 signaling in epidermal cells. J. Biol. Chem. 283, 137-144 (2008).
13. Tao, M., Scacheri, P. C., Marinis, J. M., Harhaj, E. W., Matesic, L. E. & Abbott, D. W. ITCH K63-ubiquitinates the NOD2 binding protein, RIP2, to influence inflammatory signaling pathways. Curr. Biol. 19, 1255-1263 (2009).
14. Tigno-Aranjuez, J. T., Asara, J. M. & Abbott, D. W. Inhibition of RIP2's tyrosine kinase activity limits NOD2-driven cytokine responses. Genes Dev. 24, 2666-2677 (2010).
15. Windheim, M., Lang, C., Peggie, M., Plater, L. A. & Cohen, P. Molecular mechanisms involved in the regulation of cytokine production by muramyl dipeptide. Biochem. J. 404, 179-190 (2007). (Pubitemid 46849589)
16. Nembrini, C. et al. The kinase activity of Rip2 determines its stability and consequently Nod1-and Nod2-mediated immune responses. J. Biol. Chem. 284, 19183-19188 (2009).
17. Clark, N. M., Marinis, J. M., Cobb, B. A. & Abbott, D. W. MEKK4 sequesters RIP2 to dictate NOD2 signal specificity. Curr. Biol. 18, 1402-1408 (2008).
18. Barnich, N., Aguirre, J. E., Reinecker, H. C., Xavier, R. & Podolsky, D. K. Membrane recruitment of NOD2 in intestinal epithelial cells is essential for nuclear factor-{kappa}B activation in muramyl dipeptide recognition. J. Cell. Biol. 170, 21-26 (2005). (Pubitemid 40994092)
19. Eitel, J. et al. Beta-PIX and Rac1 GTPase mediate trafficking and negative regulation of NOD2. J. Immunol. 181, 2664-2671 (2008).
20. Sabbah, A. et al. Activation of innate immune antiviral responses by Nod2. Nat. Immunol. 10, 1073-1080 (2009).
21. Watanabe, T. et al. NOD1 contributes to mouse host defense against Helicobacter pylori via induction of type I IFN and activation of the ISGF3 signaling pathway. J. Clin. Invest. 120, 1645-1662 (2010).
22. McDonald, C. et al. A role for Erbin in the regulation of Nod2-dependent NF-kappaB signaling. J. Biol. Chem. 280, 40301-40309 (2005). (Pubitemid 41779167)
23. Yamamoto-Furusho, J. K., Barnich, N., Xavier, R., Hisamatsu, T. & Podolsky, D. K. Centaurin beta1 down-regulates nucleotide-binding oligomerization domains 1-and 2-dependent NF-kappaB activation. J. Biol. Chem. 281, 36060-36070 (2006). (Pubitemid 46041339)
24. Bielig, H. et al. A function for AAMP in Nod2-mediated NF-kappaB activation. Mol. Immunol. 46, 2647-2654 (2009).
25. Hsu, Y. M. et al. The adaptor protein CARD9 is required for innate immune responses to intracellular pathogens. Nat. Immunol. 8, 198-205 (2007).
26. Yeretssian, G. et al. Non-apoptotic role of BID in inflammation and innate immunity. Nature 474, 96-99 (2011).
27. Hasegawa, M. et al. Mechanism of ASC-mediated apoptosis: bid-dependent apoptosis in type II cells. Oncogene 26, 1748-1756 (2007). (Pubitemid 46426195)
28. Mizushima, N., Levine, B., Cuervo, A. M. & Klionsky, D. J. Autophagy fights disease through cellular self-digestion. Nature 451, 1069-1075 (2008). (Pubitemid 351317450)
29. Travassos, L. H. et al. Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry. Nat. Immunol. 11, 55-62 (2010).
30. Cooney, R. et al. NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation. Nat. Med. 16, 90-97 (2010).
31. Deretic, V. Multiple regulatory and effector roles of autophagy in immunity. Curr. Opin. Immunol. 21, 53-62 (2009).
32. Watanabe, T., Kitani, A., Murray, P. J. & Strober, W. NOD2 is a negative regulator of Toll-like receptor 2-mediated T helper type 1 responses. Nat. Immunol. 5, 800-808 (2004). (Pubitemid 39172973)
33. Fritz, J. H. et al. 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 (2005). (Pubitemid 41179767)
34. Hirata, N. et al. Selective synergy in anti-inflammatory cytokine production upon cooperated signaling via TLR4 and TLR2 in murine conventional dendritic cells. Mol. Immunol. 45, 2734-2742 (2008).
35. Leber, J. H., Crimmins, G. T., Raghavan, S., Meyer-Morse, N. P., Cox, J. S. & Portnoy, D. A. Distinct TLR-and NLR-mediated transcriptional responses to an intracellular pathogen. PLoS Pathog. 4, e6 (2008).
36. Kim, Y. G., Park, J. H., Shaw, M. H., Franchi, L., Inohara, N. & Nunez, G. The cytosolic sensors Nod1 and Nod2 are critical for bacterial recognition and host defense after exposure to Toll-like receptor ligands. Immunity 28, 246-257 (2008).
37. Hsu, L. C. et al. A NOD2-NALP1 complex mediates caspase-1-dependent IL-1beta secretion in response to Bacillus anthracis infection and muramyl dipeptide. Proc. Natl Acad. Sci. USA 105, 7803-7808 (2008).
38. Pan, Q. et al. MDP-induced interleukin-1beta processing requires Nod2 and CIAS1/NALP3. J. Leukoc. Biol. 82, 177-183 (2007). (Pubitemid 47026429)
39. Toma, C. et al. Pathogenic Vibrio activate NLRP3 inflammasome via cytotoxins and TLR/nucleotide-binding oligomerization domain-mediated NF-kappa B signaling. J. Immunol. 184, 5287-5297 (2010).
40. Kullberg, B. J. et al. Crohn's disease patients homozygous for the 3020insC NOD2 mutation have a defective NOD2/TLR4 cross-tolerance to intestinal stimuli. Immunology 123, 600-605 (2008). (Pubitemid 351280974)
41. Hedl, M., Li, J., Cho, J. H. & Abraham, C. Chronic stimulation of Nod2 mediates tolerance to bacterial products. Proc. Natl Acad. Sci. USA 104, 19440-19445 (2007).
42. Hedl, M. & Abraham, C. Secretory mediators regulate Nod2-induced tolerance in human macrophages. Gastroenterology 140, 231-241 (2010).
43. Watanabe, T., Kitani, A., Murray, P. J., Wakatsuki, Y., Fuss, I. J. & Strober, W. Nucleotide binding oligomerization domain 2 deficiency leads to dysregulated TLR2 signaling and induction of antigen-specific colitis. Immunity 25, 473-485 (2006). (Pubitemid 44355006)
44. Yang, Z. et al. NOD2 transgenic mice exhibit enhanced MDP-mediated down-regulation of TLR2 responses and resistance to colitis induction. Gastroenterology 133, 1510-1521 (2007). (Pubitemid 350029733)
45. Watanabe, T. et al. Muramyl dipeptide activation of nucleotide-binding oligomerization domain 2 protects mice from experimental colitis. J. Clin. Invest. 118, 545-559 (2008). (Pubitemid 351206545)
46. Penack, O. et al. NOD2 regulates hematopoietic cell function during graft-vs.-host disease. J. Exp. Med. 206, 2101-2110 (2009).
47. Negishi, H. et al. Negative regulation of Toll-like-receptor signaling by IRF-4. Proc. Natl Acad. Sci. USA 102, 15989-15994 (2005). (Pubitemid 41552855)
48. Kobayashi, K., Hernandez, L. D., Galan, J. E., Janeway, C. A. Jr, Medzhitov, R. & Flavell, R. A. IRAK-M is a negative regulator of Toll-like receptor signaling. Cell 110, 191-202 (2002). (Pubitemid 34876547)
49. Ogura, Y. et al. Expression of NOD2 in Paneth cells: a possible link to Crohn's ileitis. Gut 52, 1591-1597 (2003). (Pubitemid 37363443)
50. Biswas, A. et al. Induction and rescue of Nod2-dependent Th1-driven granulomatous inflammation of the ileum. Proc. Natl Acad. Sci. USA 107, 14739-14744 (2010).
51. Hruz, P. et al. NOD2 contributes to cutaneous defense against Staphylococcus aureus through alpha-toxin-dependent innate immune activation. Proc. Natl Acad. Sci. USA 106, 12873-12878 (2009).
52. Shimada, K. et al. The NOD/RIP2 pathway is essential for host defenses against Chlamydophila pneumoniae lung infection. PLoS Pathog. 5, e1000379 (2009).
53. Shaw, M. H. et al. T cell-intrinsic role of Nod2 in promoting type 1 immunity to Toxoplasma gondii. Nat. Immunol. 10, 1267-1274 (2009).
54. Ferwerda, G. et al. NOD2 and toll-like receptors are nonredundant recognition systems of Mycobacterium tuberculosis. PLoS Pathog. 1, 279-285 (2005).
55. Coulombe, F. et al. Increased NOD2-mediated recognition of N-glycolyl muramyl dipeptide. J. Exp. Med. 206, 1709-1716 (2009).
56. Pandey, A. K. et al. NOD2, RIP2 and IRF5 play a critical role in the type I interferon response to Mycobacterium tuberculosis. PLoS Pathog. 5, e1000500 (2009).
57. Divangahi, M. et al. NOD2-deficient mice have impaired resistance to Mycobacterium tuberculosis infection through defective innate and adaptive immunity. J. Immunol. 181, 7157-7165 (2008).
58. Gandotra, S., Jang, S., Murray, P. J., Salgame, P. & Ehrt, S. Nucleotide-binding oligomerization domain protein 2-deficient mice control infection with Mycobacterium tuberculosis. Infect. Immun. 75, 5127-5134 (2007). (Pubitemid 350033599)
59. Petnicki-Ocwieja, T. et al. Nod2 suppresses Borrelia burgdorferi mediated murine Lyme arthritis and carditis through the induction of tolerance. PLoS One. 6, e17414 (2010).
60. Dugan, J. W. et al. Nucleotide oligomerization domain-2 interacts with 2'-5'-oligoadenylate synthetase type 2 and enhances RNase-L function in THP-1 cells. Mol. Immunol. 47, 560-566 (2009)
61. Magalhaes, J. G. et al. Nod2-dependent Th2 polarization of antigen-specific immunity. J. Immunol. 181, 7925-7935 (2008).
62. Fritz, J. H. et al. Nod1-mediated innate immune recognition of peptidoglycan contributes to the onset of adaptive immunity Immunity 26, 445-459 (2007)
63. Van Beelen, A. J. et al. Stimulation of the intracellular bacterial sensor NOD2 programs dendritic cells to promote interleukin-17 production in human memory T cells. Immunity 27, 660-669 (2007).
64. Strober, W., Fuss, I. & Mannon, P. The fundamental basis of inflammatory bowel disease. J. Clin. Invest. 117, 514-521 (2007) (Pubitemid 46348505)
65. Wehkamp, J. et al. NOD2 (CARD15) mutations in Crohn's disease are associated with diminished mucosal alpha-defensin expression. Gut 53, 1658-1664 (2004). (Pubitemid 39434112)
66. Strober, W. The multifaceted influence of the mucosal microflora on mucosal dendritic cell responses. Immunity 31, 377-388 (2009).
67. Boirivant, M. et al. A transient breach in the epithelial barrier leads to regulatory T-cell generation and resistance to experimental colitis. Gastroenterology 135, 1612-1623.e5 (2008).
68. Strober, W. Adherent-invasive E. coli in Crohn disease: bacterial " agent provocateur ". J. Clin. Invest. 121, 841-844 (2011).
69. Chassaing, B. et al. Crohn disease-associated adherent-invasive E. coli bacteria target mouse and human Peyer's patches via long polar fimbriae. J. Clin. Invest. 121, 966-975 (2011).
70. Garrett, W. S. et al. Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system. Cell 131, 33-45 (2007) (Pubitemid 47505255)
71. Wehkamp, J. et al. The Paneth cell alpha-defensin deficiency of ileal Crohn's disease is linked to Wnt/Tcf-4. J. Immunol. 179, 3109-3118 (2007).
72. Simms, L A, Doecke, J. D., Walsh, M. D., Huang, N., Fowler, E. V & Radford-Smith, G. L. Reduced alpha-defensin expression is associated with inflammation and not NOD2 mutation status in ileal Crohn's disease. Gut 57, 903-910 (2008) (Pubitemid 351919524)
73. Noguchi, E., Homma, Y, Kang, X., Netea, M. G. & Ma, X. A Crohn's disease-associated NOD2 mutation suppresses transcription of human IL10 by inhibiting activity of the nuclear ribonucleoprotein hnRNP-A1 Nat. Immunol. 10, 471-479 (2009).
74. Maeda, S. et al. Nod2 mutation in Crohn's disease potentiates NF-kappaB activity and IL-1beta processing. Science 307, 734-738 (2005) (Pubitemid 40194645)
75. Ferwerda, G. et al. Engagement of NOD2 has a dual effect on proIL-1beta mRNA transcription and secretion of bioactive IL-1beta. Eur. J. Immunol. 38, 184-191 (2008)
76. Barreau, F. et al. CARD15/NOD2 is required for Peyer's patches homeostasis in mice. PLoS One 2, e523 (2007).
77. Barreau, F. et al. Nod2 regulates the host response towards microflora by modulating T cell function and epithelial permeability in mouse Peyer's patches. Gut 59, 207-217 (2010).