Nod2

Summary

Gene Symbol: Nod2
Description: nucleotide-binding oligomerization domain containing 2
Alias: ACUG, BLAU, Card15, F830032C23Rik, IBD1, Nlrc2, nucleotide-binding oligomerization domain-containing protein 2, caspase recruitment domain family, member 15, caspase recruitment domain-containing protein 15
Species: mouse
Products:     Nod2

Top Publications

  1. Finney C, Lu Z, Lebourhis L, Philpott D, Kain K. Disruption of Nod-like receptors alters inflammatory response to infection but does not confer protection in experimental cerebral malaria. Am J Trop Med Hyg. 2009;80:718-22 pubmed
    ..We therefore demonstrate for the first time that Nod proteins are activated in response to parasites, and they play a role in regulating host inflammatory responses during malaria infection. ..
  2. Chauhan V, Sterka D, Furr S, Young A, Marriott I. NOD2 plays an important role in the inflammatory responses of microglia and astrocytes to bacterial CNS pathogens. Glia. 2009;57:414-23 pubmed publisher
    ..demonstrated that microglia and astrocytes constitutively express nucleotide-binding oligomerization domain-2 (NOD2), a member of the novel nucleotide-binding domain leucine-rich repeat region containing a family of proteins (NLR) ..
  3. Müller Anstett M, Muller P, Albrecht T, Nega M, Wagener J, Gao Q, et al. Staphylococcal peptidoglycan co-localizes with Nod2 and TLR2 and activates innate immune response via both receptors in primary murine keratinocytes. PLoS ONE. 2010;5:e13153 pubmed publisher
    In mammalian host cells staphylococcal peptidoglycan (PGN) is recognized by Nod2. Whether PGN is also recognized by TLR2 is disputed...
  4. Jamontt J, Petit S, Clark N, Parkinson S, Smith P. Nucleotide-binding oligomerization domain 2 signaling promotes hyperresponsive macrophages and colitis in IL-10-deficient mice. J Immunol. 2013;190:2948-58 pubmed publisher
    ..oligomerization domain (NOD) 2 is an intracellular receptor of bacterial peptidoglycan products, and, although NOD2 mutations are associated with Crohn's disease, the precise role of NOD2 in the development of intestinal ..
  5. Stockinger S, Reutterer B, Schaljo B, Schellack C, Brunner S, Materna T, et al. IFN regulatory factor 3-dependent induction of type I IFNs by intracellular bacteria is mediated by a TLR- and Nod2-independent mechanism. J Immunol. 2004;173:7416-25 pubmed
    ..Expression of Nod2, a candidate receptor for intracellular bacteria, increased during infection, but the protein was not required for ..
  6. Davis K, Nakamura S, Weiser J. Nod2 sensing of lysozyme-digested peptidoglycan promotes macrophage recruitment and clearance of S. pneumoniae colonization in mice. J Clin Invest. 2011;121:3666-76 pubmed publisher
    ..in mice lacking digestion of peptidoglycan by lysozyme (LysM) and cytosolic sensing of the products of digestion by Nod2. Ex vivo macrophages produced CCL2 following bacterial uptake, digestion by LysM, and sensing of peptidoglycan by ..
  7. Mariathasan S, Weiss D, Newton K, McBride J, O Rourke K, Roose Girma M, et al. Cryopyrin activates the inflammasome in response to toxins and ATP. Nature. 2006;440:228-32 pubmed
    ..Therefore, cryopyrin is essential for inflammasome activation in response to signalling pathways triggered specifically by ATP, nigericin, maitotoxin, S. aureus or L. monocytogenes. ..
  8. Rosenzweig H, Jann M, Glant T, Martin T, Planck S, van Eden W, et al. Activation of nucleotide oligomerization domain 2 exacerbates a murine model of proteoglycan-induced arthritis. J Leukoc Biol. 2009;85:711-8 pubmed publisher
    ..Notably, mutations in NOD2 cause the inherited granulomatous disease of the joints called Blau syndrome, thereby linking NOD2 with joint disease as well...
  9. Liu X, Chauhan V, Young A, Marriott I. NOD2 mediates inflammatory responses of primary murine glia to Streptococcus pneumoniae. Glia. 2010;58:839-47 pubmed publisher
    ..demonstrated that microglia and astrocytes constitutively express nucleotide-binding oligomerization domain-2 (NOD2), a member of the novel nucleotide-binding domain leucine-rich repeat region-containing family of proteins (NLR) ..

More Information

Publications78

  1. Röhrl J, Yang D, Oppenheim J, Hehlgans T. Identification and Biological Characterization of Mouse beta-defensin 14, the orthologue of human beta-defensin 3. J Biol Chem. 2008;283:5414-9 pubmed publisher
    ..expression of mBD14 seems to be regulated by activation of the intracellular pattern recognition receptor NOD2/CARD15 as revealed by reporter gene analysis...
  2. Barreau F, Madre C, Meinzer U, Berrebi D, Dussaillant M, Merlin F, et al. Nod2 regulates the host response towards microflora by modulating T cell function and epithelial permeability in mouse Peyer's patches. Gut. 2010;59:207-17 pubmed publisher
    Nucleotide oligomerisation domain 2 (NOD2) mutations are associated with susceptibility to Crohn's disease and graft-versus-host disease, two human disorders related with dysfunctions of Peyer's patches (PPs)...
  3. Body Malapel M, Dharancy S, Berrebi D, Louvet A, Hugot J, Philpott D, et al. NOD2: a potential target for regulating liver injury. Lab Invest. 2008;88:318-27 pubmed publisher
    The recent discovery of bacterial receptors such as NOD2 that contribute to crosstalk between innate and adaptive immune systems in the digestive tract constitutes an important challenge in our understanding of liver injury mechanisms...
  4. Abbott D, Yang Y, Hutti J, Madhavarapu S, Kelliher M, Cantley L. Coordinated regulation of Toll-like receptor and NOD2 signaling by K63-linked polyubiquitin chains. Mol Cell Biol. 2007;27:6012-25 pubmed
    ..inflammatory disorder in which this process may be faulty as the major Crohn's disease-associated protein, NOD2 (nucleotide oligomerization domain 2), regulates the formation of K63-linked polyubiquitin chains on the I kappa ..
  5. Berrington W, Iyer R, Wells R, Smith K, Skerrett S, Hawn T. NOD1 and NOD2 regulation of pulmonary innate immunity to Legionella pneumophila. Eur J Immunol. 2010;40:3519-27 pubmed publisher
    The role of nucleotide-binding oligomerization domain-1 (NOD1) and nucleotide-binding oligomerization domain-2 (NOD2), cytoplasmic receptors which detect bacterial cell wall molecules, in pulmonary innate immune responses is poorly ..
  6. Manni M, Ding W, Stohl L, Granstein R. Muramyl dipeptide induces Th17 polarization through activation of endothelial cells. J Immunol. 2011;186:3356-63 pubmed publisher
    ..These results are important for the understanding of Th17-related disorders of the skin such as psoriasis. ..
  7. Watanabe T, Kitani A, Murray P, Wakatsuki Y, Fuss I, Strober W. Nucleotide binding oligomerization domain 2 deficiency leads to dysregulated TLR2 signaling and induction of antigen-specific colitis. Immunity. 2006;25:473-85 pubmed
    ..conditions leading to the development of colitis in mice with nucleotide binding oligomerization domain 2 (NOD2) deficiency, a susceptibility factor in Crohn's disease...
  8. Scurrell E, Stanley R, Schöniger S. Immunohistochemical detection of NOD1 and NOD2 in the healthy murine and canine eye. Vet Ophthalmol. 2009;12:269-75 pubmed publisher
    The innate immune system provides the immediate defense against pathogens. NOD1 and NOD2 proteins are intracytoplasmic signaling receptors of the innate immune system and recognize conserved microbial molecular structures...
  9. Couturier Maillard A, Secher T, Rehman A, Normand S, De Arcangelis A, Haesler R, et al. NOD2-mediated dysbiosis predisposes mice to transmissible colitis and colorectal cancer. J Clin Invest. 2013;123:700-11 pubmed publisher
    ..Here, we show that dysbiosis caused by Nod2 deficiency gives rise to a reversible, communicable risk of colitis and colitis-associated carcinogenesis in mice...
  10. Watanabe T, Asano N, Murray P, Ozato K, Tailor P, Fuss I, et al. Muramyl dipeptide activation of nucleotide-binding oligomerization domain 2 protects mice from experimental colitis. J Clin Invest. 2008;118:545-59 pubmed publisher
    The mechanisms underlying the susceptibility of individuals with caspase recruitment domain 15 (CARD15) mutations and corresponding abnormalities of nucleotide-binding oligomerization domain 2 (NOD2) protein to Crohn disease are still ..
  11. Herskovits A, Auerbuch V, Portnoy D. Bacterial ligands generated in a phagosome are targets of the cytosolic innate immune system. PLoS Pathog. 2007;3:e51 pubmed
    ..bacterial ligands in the phago-lysosome and was largely dependent on nucleotide-binding oligomerization domain 2 (NOD2), a cytosolic receptor known to respond to bacterial peptidoglycan fragments...
  12. Kim Y, Kamada N, Shaw M, Warner N, Chen G, Franchi L, et al. The Nod2 sensor promotes intestinal pathogen eradication via the chemokine CCL2-dependent recruitment of inflammatory monocytes. Immunity. 2011;34:769-80 pubmed publisher
    The intracellular sensor Nod2 is activated in response to bacteria, and the impairment of this response is linked to Crohn's disease. However, the function of Nod2 in host defense remains poorly understood...
  13. Kanneganti T, Lamkanfi M, Kim Y, Chen G, Park J, Franchi L, et al. Pannexin-1-mediated recognition of bacterial molecules activates the cryopyrin inflammasome independent of Toll-like receptor signaling. Immunity. 2007;26:433-43 pubmed
  14. Travassos L, Carneiro L, Ramjeet M, Hussey S, Kim Y, Magalhaes J, et al. Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry. Nat Immunol. 2010;11:55-62 pubmed publisher
    ..Here we demonstrated that the intracellular sensors Nod1 and Nod2 are critical for the autophagic response to invasive bacteria...
  15. Schertzer J, Tamrakar A, Magalhaes J, Pereira S, Bilan P, Fullerton M, et al. NOD1 activators link innate immunity to insulin resistance. Diabetes. 2011;60:2206-15 pubmed publisher
    ..mimetics of meso-diaminopimelic acid-containing PGN or the minimal bioactive PGN motif, which activate NOD1 and NOD2, respectively...
  16. Caetano B, Biswas A, Lima D, Benevides L, Mineo T, Horta C, et al. Intrinsic expression of Nod2 in CD4+ T lymphocytes is not necessary for the development of cell-mediated immunity and host resistance to Toxoplasma gondii. Eur J Immunol. 2011;41:3627-31 pubmed publisher
    b>Nod2 belongs to the nucleotide-binding domain leucine-rich repeat family of proteins and senses bacterial cell wall components to initiate innate immune responses against various pathogens...
  17. Hruz P, Zinkernagel A, Jenikova G, Botwin G, Hugot J, Karin M, et al. NOD2 contributes to cutaneous defense against Staphylococcus aureus through alpha-toxin-dependent innate immune activation. Proc Natl Acad Sci U S A. 2009;106:12873-8 pubmed publisher
    ..aureus in vitro, but the physiological significance of these observations is not well defined. Here we show that NOD2-deficient mice exhibit a delayed but ultimately exacerbated ulcerative response and impaired bacterial clearance ..
  18. Biswas A, Liu Y, Hao L, Mizoguchi A, Salzman N, Bevins C, et al. Induction and rescue of Nod2-dependent Th1-driven granulomatous inflammation of the ileum. Proc Natl Acad Sci U S A. 2010;107:14739-44 pubmed publisher
    Mutations in the NOD2 gene are strong genetic risk factors for ileal Crohn's disease. However, the mechanism by which these mutations predispose to intestinal inflammation remains a subject of controversy...
  19. Marriott I, Rati D, McCall S, Tranguch S. Induction of Nod1 and Nod2 intracellular pattern recognition receptors in murine osteoblasts following bacterial challenge. Infect Immun. 2005;73:2967-73 pubmed
    ..we demonstrate that murine osteoblasts express the novel intracellular pattern recognition receptors Nod1 and Nod2. Levels of mRNA encoding Nod molecules and protein expression are significantly and differentially increased from ..
  20. Kim Y, Park J, Shaw M, 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. 2008;28:246-57 pubmed publisher
    The cytosolic sensors Nod1 and Nod2 and Toll-like receptors (TLRs) activate defense signaling pathways in response to microbial stimuli...
  21. Sterka D, Rati D, Marriott I. Functional expression of NOD2, a novel pattern recognition receptor for bacterial motifs, in primary murine astrocytes. Glia. 2006;53:322-30 pubmed
    ..We show that isolated cultures of murine astrocytes constitutively express robust levels of NOD2, a molecule that can recognize a minimal peptidoglycan motif...
  22. Shimada K, Chen S, Dempsey P, Sorrentino R, Alsabeh R, Slepenkin A, et al. The NOD/RIP2 pathway is essential for host defenses against Chlamydophila pneumoniae lung infection. PLoS Pathog. 2009;5:e1000379 pubmed publisher
    ..Both Nod1(-/-) and Nod2(-/-) mice also showed delayed bacterial clearance, suggesting that C...
  23. Abbott D, Wilkins A, Asara J, Cantley L. The Crohn's disease protein, NOD2, requires RIP2 in order to induce ubiquitinylation of a novel site on NEMO. Curr Biol. 2004;14:2217-27 pubmed
    ..The function of the Crohn's disease protein, NOD2, highlights the biphasic nature of the pathology of Crohn's disease...
  24. Frutuoso M, Hori J, Pereira M, Junior D, Sonego F, Kobayashi K, et al. The pattern recognition receptors Nod1 and Nod2 account for neutrophil recruitment to the lungs of mice infected with Legionella pneumophila. Microbes Infect. 2010;12:819-27 pubmed publisher
    ..By using mice deficient for Nod1, Nod2, and Rip2, we found that these receptors accounted for NE recruitment to the lungs of infected mice...
  25. Girardin S, Boneca I, Viala J, Chamaillard M, Labigne A, Thomas G, et al. Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection. J Biol Chem. 2003;278:8869-72 pubmed
    b>Nod2 activates the NF-kappaB pathway following intracellular stimulation by bacterial products...
  26. Selvanantham T, Escalante N, Cruz Tleugabulova M, Fiéve S, Girardin S, Philpott D, et al. Nod1 and Nod2 enhance TLR-mediated invariant NKT cell activation during bacterial infection. J Immunol. 2013;191:5646-54 pubmed publisher
    ..We show that the cytosolic peptidoglycan-sensing receptors Nod1 and Nod2 are necessary for optimal IFN-? production by iNKT cells, as well as NK cells...
  27. Coulombe F, Divangahi M, Veyrier F, de Léséleuc L, Gleason J, Yang Y, et al. Increased NOD2-mediated recognition of N-glycolyl muramyl dipeptide. J Exp Med. 2009;206:1709-16 pubmed publisher
    Peptidoglycan-derived muramyl dipeptide (MDP) activates innate immunity via the host sensor NOD2. Although MDP is N-acetylated in most bacteria, mycobacteria and related Actinomycetes convert their MDP to an N-glycolylated form through ..
  28. Iwanaga Y, Davey M, Martin T, Planck S, DePriest M, Baugh M, et al. Cloning, sequencing and expression analysis of the mouse NOD2/CARD15 gene. Inflamm Res. 2003;52:272-6 pubmed
    Mutations in the human NOD2/CARD15 gene have been associated with Crohn's disease and Blau syndrome...
  29. Yang Y, Yin C, Pandey A, Abbott D, Sassetti C, Kelliher M. NOD2 pathway activation by MDP or Mycobacterium tuberculosis infection involves the stable polyubiquitination of Rip2. J Biol Chem. 2007;282:36223-9 pubmed
    ..We find Rip2 required for Nod2-mediated NF-kappaB activation and to a lesser extent mitogen-activated protein kinase activation...
  30. Oh S, Kim J, Chung D. NOD2-mediated suppression of CD55 on neutrophils enhances C5a generation during polymicrobial sepsis. PLoS Pathog. 2013;9:e1003351 pubmed publisher
    ..C5a, which has harmful effects in sepsis, interacts with innate proteins. However, whether NOD2 regulates C5a generation during sepsis remains to be determined...
  31. Divangahi M, Mostowy S, Coulombe F, Kozak R, Guillot L, Veyrier F, et al. NOD2-deficient mice have impaired resistance to Mycobacterium tuberculosis infection through defective innate and adaptive immunity. J Immunol. 2008;181:7157-65 pubmed
    NOD2/CARD15 mediates innate immune responses to mycobacterial infection. However, its role in the regulation of adaptive immunity has remained unknown...
  32. Kapetanovic R, Jouvion G, Fitting C, Parlato M, Blanchet C, Huerre M, et al. Contribution of NOD2 to lung inflammation during Staphylococcus aureus-induced pneumonia. Microbes Infect. 2010;12:759-67 pubmed publisher
    ..In this work, we investigated the role of NOD2 in S. aureus-induced pneumonia. We found that the absence of NOD2 affected weight loss and recovery speed...
  33. Kayagaki N, Warming S, Lamkanfi M, Vande Walle L, Louie S, Dong J, et al. Non-canonical inflammasome activation targets caspase-11. Nature. 2011;479:117-21 pubmed publisher
    ..These data highlight a unique pro-inflammatory role for caspase-11 in the innate immune response to clinically significant bacterial infections. ..
  34. Kobayashi K, Chamaillard M, Ogura Y, Henegariu O, Inohara N, Nunez G, et al. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science. 2005;307:731-4 pubmed
    The gene encoding the Nod2 protein is frequently mutated in Crohn's disease (CD) patients, although the physiological function of Nod2 in the intestine remains elusive...
  35. Hasegawa M, Yamazaki T, Kamada N, Tawaratsumida K, Kim Y, Nunez G, et al. Nucleotide-binding oligomerization domain 1 mediates recognition of Clostridium difficile and induces neutrophil recruitment and protection against the pathogen. J Immunol. 2011;186:4872-80 pubmed publisher
    ..Nod1(-/-), but not Nod2(-/-), mice exhibited increased lethality in response to C...
  36. Yang Z, Fuss I, Watanabe T, Asano N, Davey M, Rosenbaum J, et al. NOD2 transgenic mice exhibit enhanced MDP-mediated down-regulation of TLR2 responses and resistance to colitis induction. Gastroenterology. 2007;133:1510-21 pubmed
    Mutations in the CARD15 gene encoding NOD2 are susceptibility factors in Crohn's disease. We explored the mechanism of this susceptibility using mice that over express NOD2...
  37. Watanabe T, Kitani A, Murray P, Strober W. NOD2 is a negative regulator of Toll-like receptor 2-mediated T helper type 1 responses. Nat Immunol. 2004;5:800-8 pubmed
    The mechanism by which mutations in CARD15, which encodes nucleotide-binding oligomerization domain 2 (NOD2), cause Crohn disease is poorly understood...
  38. Miller J, Maylor Hagen H, Ma Y, Weis J, Weis J. The Lyme disease spirochete Borrelia burgdorferi utilizes multiple ligands, including RNA, for interferon regulatory factor 3-dependent induction of type I interferon-responsive genes. Infect Immun. 2010;78:3144-53 pubmed publisher
    ..burgdorferi-stimulated BMDMs occurs independently of the adapter TRIF and of the cytoplasmic sensor NOD2. In contrast, B...
  39. Maeda S, Hsu L, Liu H, Bankston L, Iimura M, Kagnoff M, et al. Nod2 mutation in Crohn's disease potentiates NF-kappaB activity and IL-1beta processing. Science. 2005;307:734-8 pubmed
    Variants of NOD2, an intracellular sensor of bacteria-derived muramyl dipeptide (MDP), increase susceptibility to Crohn's disease (CD)...
  40. Shaw P, Barr M, Lukens J, McGargill M, Chi H, Mak T, et al. Signaling via the RIP2 adaptor protein in central nervous system-infiltrating dendritic cells promotes inflammation and autoimmunity. Immunity. 2011;34:75-84 pubmed publisher
    ..Here we report that the progression of EAE was dependent on the intracellular PGN sensors NOD1 and NOD2 and their common downstream adaptor molecule, receptor interacting protein 2 (RIP2; also known as RIPK2 and RICK)...
  41. Pan Q, Mathison J, Fearns C, Kravchenko V, da Silva Correia J, Hoffman H, et al. MDP-induced interleukin-1beta processing requires Nod2 and CIAS1/NALP3. J Leukoc Biol. 2007;82:177-83 pubmed
    ..b>Nod2 also plays a role in some autoinflammatory diseases...
  42. Liu X, Chauhan V, Marriott I. NOD2 contributes to the inflammatory responses of primary murine microglia and astrocytes to Staphylococcus aureus. Neurosci Lett. 2010;474:93-8 pubmed publisher
    We have recently demonstrated that microglia and astrocytes express nucleotide-binding oligomerization domain-2 (NOD2), a novel cytosolic pattern recognition receptor for bacterial motifs, and we have shown that this intracellular ..
  43. Hsu L, Ali S, McGillivray S, Tseng P, Mariathasan S, Humke E, 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 U S A. 2008;105:7803-8 pubmed publisher
    b>NOD2, a NOD-like receptor (NLR), is an intracellular sensor of bacterial muramyl dipeptide (MDP) that was suggested to promote secretion of the proinflammatory cytokine IL-1beta...
  44. Ogura Y, Saab L, Chen F, Benito A, Inohara N, Nunez G. Genetic variation and activity of mouse Nod2, a susceptibility gene for Crohn's disease. Genomics. 2003;81:369-77 pubmed
    Genetic variation in human Nod2 has been associated with susceptibility to Crohn's disease. The mouse Nod2 locus is located at chromosome 8 and composed of 12 exons, 11 of which encode the Nod2 protein...
  45. Anand P, Tait S, Lamkanfi M, Amer A, Nunez G, Pages G, et al. TLR2 and RIP2 pathways mediate autophagy of Listeria monocytogenes via extracellular signal-regulated kinase (ERK) activation. J Biol Chem. 2011;286:42981-91 pubmed publisher
    ..monocytogenes. Inefficient autophagy in Tlr2(-/-) and Nod2(-/-) macrophages led to a defect in bacteria colocalization with the autophagosomal marker GFP-LC3...
  46. Chattoraj P, Yang Q, Khandai A, Al Hendy O, Ismail N. TLR2 and Nod2 mediate resistance or susceptibility to fatal intracellular Ehrlichia infection in murine models of ehrlichiosis. PLoS ONE. 2013;8:e58514 pubmed publisher
    ..cytokines and chemokines, which was associated with increased expression levels of Toll-like receptor-2 (TLR2), Nod2, MyD88, nuclear factor-kappa B (NF-kB), Caspase 4, NLRP1, NLRP12, Pycard, and IL-1?, suggesting enhanced TLR ..
  47. Conforti Andreoni C, Beretta O, Licandro G, Qian H, Urbano M, Vitulli F, et al. Synergism of NOD2 and NLRP3 activators promotes a unique transcriptional profile in murine dendritic cells. J Leukoc Biol. 2010;88:1207-16 pubmed publisher
    ..study, we employed microarrays to investigate in DCs the regulation of gene transcription mediated by activation of NOD2 and NLRP3 pathways using MDP and MSU...
  48. Magalhaes J, Fritz J, Le Bourhis L, Sellge G, Travassos L, Selvanantham T, et al. Nod2-dependent Th2 polarization of antigen-specific immunity. J Immunol. 2008;181:7925-35 pubmed
    ..Here, we examined the unfolding of the adaptive immune response induced by Nod2 in vivo upon activation by its specific ligand, muramyl dipeptide, a component of peptidoglycan...
  49. Ferwerda G, Kullberg B, de Jong D, Girardin S, Langenberg D, van Crevel R, et al. Mycobacterium paratuberculosis is recognized by Toll-like receptors and NOD2. J Leukoc Biol. 2007;82:1011-8 pubmed
    ..mutations in the intracellular pathogen recognition receptor (PRR) nucleotide-binding oligomerization domain 2 (NOD2). The aim of this study is to investigate the PRR involved in the recognition of M. paratuberculosis...
  50. Martinon F, Tschopp J. NLRs join TLRs as innate sensors of pathogens. Trends Immunol. 2005;26:447-54 pubmed
  51. Deshmukh H, Hamburger J, Ahn S, McCafferty D, Yang S, Fowler V. Critical role of NOD2 in regulating the immune response to Staphylococcus aureus. Infect Immun. 2009;77:1376-82 pubmed publisher
    b>NOD2 (the nucleotide-binding oligomerization domain containing protein 2) is known to be involved in host recognition of bacteria, although its role in the host response to Staphylococcus aureus infection is unknown...
  52. Rosenzweig H, Kawaguchi T, Martin T, Planck S, Davey M, Rosenbaum J. Nucleotide oligomerization domain-2 (NOD2)-induced uveitis: dependence on IFN-gamma. Invest Ophthalmol Vis Sci. 2009;50:1739-45 pubmed publisher
    ..Notably, NOD2 is linked to eye inflammation because mutations in NOD2 cause a granulomatous type of uveitis called Blau syndrome...
  53. Rosenzweig H, Martin T, Jann M, Planck S, Davey M, Kobayashi K, et al. NOD2, the gene responsible for familial granulomatous uveitis, in a mouse model of uveitis. Invest Ophthalmol Vis Sci. 2008;49:1518-24 pubmed publisher
    ..Specific mutations in the human NOD2 gene cause Blau syndrome, an autosomal dominant form of uveitis, arthritis, and dermatitis...
  54. Saha S, Qi J, Wang S, Wang M, Li X, Kim Y, et al. PGLYRP-2 and Nod2 are both required for peptidoglycan-induced arthritis and local inflammation. Cell Host Microbe. 2009;5:137-50 pubmed publisher
    ..We demonstrate that PGLYRP-2 and Nod2 are both required for arthritis in this model...
  55. Penack O, Smith O, Cunningham Bussel A, Liu X, Rao U, Yim N, et al. NOD2 regulates hematopoietic cell function during graft-versus-host disease. J Exp Med. 2009;206:2101-10 pubmed publisher
    Nucleotide-binding oligomerization domain 2 (NOD2) polymorphisms are independent risk factors for Crohn's disease and graft-versus-host disease (GVHD)...
  56. Clarke T, Davis K, Lysenko E, Zhou A, Yu Y, Weiser J. Recognition of peptidoglycan from the microbiota by Nod1 enhances systemic innate immunity. Nat Med. 2010;16:228-31 pubmed publisher
    ..meso-diaminopimelic acid (mesoDAP)-containing peptidoglycan found predominantly in Gram-negative bacteria), but not Nod2 (which detects peptidoglycan found in Gram-positive and Gram-negative bacteria) or Toll-like receptor 4 (Tlr4, ..
  57. Geddes K, Rubino S, Streutker C, Cho J, Magalhaes J, Le Bourhis L, et al. Nod1 and Nod2 regulation of inflammation in the Salmonella colitis model. Infect Immun. 2010;78:5107-15 pubmed publisher
    The pattern recognition molecules Nod1 and Nod2 play important roles in intestinal homeostasis; however, how these proteins impact on the development of inflammation during bacterial colitis has not been examined...
  58. Kim Y, Park J, Reimer T, Baker D, Kawai T, Kumar H, et al. Viral infection augments Nod1/2 signaling to potentiate lethality associated with secondary bacterial infections. Cell Host Microbe. 2011;9:496-507 pubmed publisher
    ..show that the TLR3/MDA5 agonist poly I:C or viral infection dramatically augments signaling via the NLRs Nod1 and Nod2 and enhances the production of proinflammatory cytokines...
  59. Werts C, Le Bourhis L, Liu J, Magalhaes J, Carneiro L, Fritz J, et al. Nod1 and Nod2 induce CCL5/RANTES through the NF-kappaB pathway. Eur J Immunol. 2007;37:2499-508 pubmed
    The Nod-like receptor proteins Nod1 and Nod2 participate in innate immune responses against bacteria through intracellular detection of peptidoglycan, a component of bacterial cell wall...
  60. Barreau F, Meinzer U, Chareyre F, Berrebi D, Niwa Kawakita M, Dussaillant M, et al. CARD15/NOD2 is required for Peyer's patches homeostasis in mice. PLoS ONE. 2007;2:e523 pubmed
    b>CARD15/NOD2 mutations are associated with susceptibility to Crohn's Disease (CD) and Graft Versus Host Disease (GVHD)...
  61. Shaw M, Reimer T, Sánchez Valdepeñas C, Warner N, Kim Y, Fresno M, et al. T cell-intrinsic role of Nod2 in promoting type 1 immunity to Toxoplasma gondii. Nat Immunol. 2009;10:1267-74 pubmed publisher
    b>Nod2 belongs to the nucleotide-binding oligomerization domain receptor (NLR) family of proteins, which function as intracellular pathogen sensors in innate immune cells...
  62. Tigno Aranjuez J, Asara J, Abbott D. Inhibition of RIP2's tyrosine kinase activity limits NOD2-driven cytokine responses. Genes Dev. 2010;24:2666-77 pubmed publisher
    Upon intracellular bacterial exposure, the Crohn's disease and sarcoidosis susceptibility protein NOD2 (nucleotide oligomerization domain protein 2) binds to the protein kinase RIP2 (receptor-interacting protein 2) to coordinate NF-?B (..
  63. Petnicki Ocwieja T, Hrncir T, Liu Y, Biswas A, Hudcovic T, Tlaskalova Hogenova H, et al. Nod2 is required for the regulation of commensal microbiota in the intestine. Proc Natl Acad Sci U S A. 2009;106:15813-8 pubmed publisher
    Mutations in the Nod2 gene are among the strongest genetic risk factors in the pathogenesis of ileal Crohn's disease, but the exact contributions of Nod2 to intestinal mucosal homeostasis are not understood...
  64. Hiemstra I, Bouma G, Geerts D, Kraal G, den Haan J. Nod2 improves barrier function of intestinal epithelial cells via enhancement of TLR responses. Mol Immunol. 2012;52:264-72 pubmed publisher
    ..shRNA knock-down studies showed that MDP recognition by Nod2 mediated the enhancement of TLR responses...
  65. Rosenzweig H, Martin T, Planck S, Galster K, Jann M, Davey M, et al. Activation of NOD2 in vivo induces IL-1beta production in the eye via caspase-1 but results in ocular inflammation independently of IL-1 signaling. J Leukoc Biol. 2008;84:529-36 pubmed publisher
    Nucleotide-binding and oligomerization domain 2 (NOD2) belongs to the emerging Nod-like receptor (NLR) family considered important in innate immunity...
  66. Meinzer U, Esmiol Welterlin S, Barreau F, Berrebi D, Dussaillant M, Bonacorsi S, et al. Nod2 mediates susceptibility to Yersinia pseudotuberculosis in mice. PLoS ONE. 2008;3:e2769 pubmed publisher
    Nucleotide oligomerisation domain 2 (NOD2) is a component of the innate immunity known to be involved in the homeostasis of Peyer patches (PPs) in mice. However, little is known about its role during gut infection in vivo...
  67. Tsai W, Huang D, Yu Y, Chen C, Lin W. Dual roles of NOD2 in TLR4-mediated signal transduction and -induced inflammatory gene expression in macrophages. Cell Microbiol. 2011;13:717-30 pubmed publisher
    b>NOD2 of the NLRs and TLR4 of the TLRs are major pattern-recognition receptors, which sense different microbial pathogens and have important roles in innate immunity...
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