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Nod2 Mutation in Crohn's Disease Potentiates NF-κB Activity and IL-1ß Processing

Science, 4 February 2005
Vol. 307, Issue 5710, p. 734-738
DOI: 10.1126/science.1103685

Nod2 Mutation in Crohn's Disease Potentiates NF-κB Activity and IL-1ß Processing

  1. Shin Maeda1,
  2. Li-Chung Hsu1,*,
  3. Hongjun Liu1,*,
  4. Laurie A. Bankston1,3,
  5. Mitsutoshi Iimura2,
  6. Martin F. Kagnoff2,
  7. Lars Eckmann2,
  8. Michael Karin1,
  1. 1 Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093–0723, USA.
  2. 2 Laboratory of Mucosal Immunology, Departments of Medicine and Pediatrics, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093–0723, USA.
  3. 3 Program on Cell Adhesion, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
  1. To whom correspondence should be addressed. E-mail: karinoffice{at}
  • * These authors contributed equally to this work.


Variants of NOD2, an intracellular sensor of bacteria-derived muramyl dipeptide (MDP), increase susceptibility to Crohn's disease (CD). These variants are thought to be defective in activation of nuclear factor κB (NF-κB) and antibacterial defenses, but CD clinical specimens display elevated NF-κB activity. To illuminate the pathophysiological function of NOD2, we introduced such a variant to the mouse Nod2 locus. Mutant mice exhibited elevated NF-κB activation in response to MDP and more efficient processing and secretion of the cytokine interleukin-1β (IL-1β). These effects are linked to increased susceptibility to bacterial-induced intestinal inflammation and identify NOD2 as a positive regulator of NF-κB activation and IL-1β secretion.

    • Received for publication 5 August 2004.
    • Accepted for publication 8 December 2004.


    S. Maeda, L.-C. Hsu, H. Liu, L. A. Bankston, M. Iimura, M. F. Kagnoff, L. Eckmann, and M. Karin, Nod2 Mutation in Crohn's Disease Potentiates NF-κB Activity and IL-1ß Processing. Science 307, 734-738 (2005).

    Nucleotide-Binding Oligomerization Domain 2 Receptor Is Expressed in Platelets and Enhances Platelet Activation and Thrombosis
    S. Zhang, S. Zhang, L. Hu, L. Zhai, R. Xue, J. Ye, L. Chen, G. Cheng, J. Mruk, S. P. Kunapuli et al.
    Circulation 131, 1160-1170 (31 March 2015)

    Perilla frutescens extract ameliorates DSS-induced colitis by suppressing proinflammatory cytokines and inducing anti-inflammatory cytokines
    H. Urushima, J. Nishimura, T. Mizushima, N. Hayashi, K. Maeda, and T. Ito
    Am. J. Physiol. Gastrointest. Liver Physiol. 308, G32-G41 (1 January 2015)

    ClC-3 chloride channel/antiporter defect contributes to inflammatory bowel disease in humans and mice
    L.-Y. Huang, Q. He, S.-J. Liang, Y.-X. Su, L.-X. Xiong, Q.-Q. Wu, Q.-Y. Wu, J. Tao, J.-P. Wang, Y.-B. Tang et al.
    Gut 63, 1587-1595 (1 October 2014)

    Robustness trade-offs and host-microbial symbiosis in the immune system
    H. Kitano, and K. Oda
    Mol Syst Biol 2, 2006.0022-2006.0022 (28 July 2014)

    CD47 fusion protein targets CD172a+ cells in Crohn's disease and dampens the production of IL-1{beta} and TNF
    N. Baba, V. Q. Van, K. Wakahara, M. Rubio, G. Fortin, B. Panzini, G. Soucy, R. Wassef, C. Richard, R. Tamaz et al.
    JEM 210, 1251-1263 (3 June 2013)

    The Therapeutic Potential of Modifying Inflammasomes and NOD-Like Receptors
    F. Di Virgilio, V. Q. Van, K. Wakahara, M. Rubio, G. Fortin, B. Panzini, G. Soucy, R. Wassef, C. Richard, R. Tamaz et al.
    Pharmacol. Rev. 65, 872-905 (16 April 2013)

    Nucleotide-Binding Oligomerization Domain 2 Signaling Promotes Hyperresponsive Macrophages and Colitis in IL-10-Deficient Mice
    J. Jamontt, S. Petit, N. Clark, S. J. Parkinson, and P. Smith
    J. Immunol. 190, 2948-2958 (15 March 2013)

    Autophagy as an innate defense against mycobacteria
    E.-K. Jo, S. Petit, N. Clark, S. J. Parkinson, and P. Smith
    Pathog Dis 67, 108-118 (1 March 2013)

    Roles of NOD1 (NLRC1) and NOD2 (NLRC2) in innate immunity and inflammatory diseases
    R. G. Correa, S. Milutinovic, and J. C. Reed
    Biosci. Rep. 32, 597-608 (1 December 2012)

    IL-1{beta} mediates chronic intestinal inflammation by promoting the accumulation of IL-17A secreting innate lymphoid cells and CD4+ Th17 cells
    M. Coccia, O. J. Harrison, C. Schiering, M. J. Asquith, B. Becher, F. Powrie, and K. J. Maloy
    JEM 209, 1595-1609 (27 August 2012)

    Novel treatment concepts for graft-versus-host disease
    D. Wolf, M. von Lilienfeld-Toal, A. M. Wolf, M. Schleuning, M. von Bergwelt-Baildon, S. A. E. Held, and P. Brossart
    Blood 119, 16-25 (5 January 2012)

    Crohn's disease: NOD2, autophagy and ER stress converge
    T. Fritz, L. Niederreiter, T. Adolph, R. S. Blumberg, and A. Kaser
    Gut 60, 1580-1588 (1 November 2011)

    Cutting Edge: Crohn's Disease-Associated Nod2 Mutation Limits Production of Proinflammatory Cytokines To Protect the Host from Enterococcus faecalis-Induced Lethality
    Y.-G. Kim, M. H. Shaw, N. Warner, J.-H. Park, F. Chen, Y. Ogura, and G. Nunez
    J. Immunol. 187, 2849-2852 (15 September 2011)

    Innate Immunity in the Small Intestine of the Preterm Infant.
    S. J. McElroy, and J.-H. Weitkamp
    Neoreviews 12, e517-e526 (1 September 2011)

    The mononuclear phagocyte system of the pig as a model for understanding human innate immunity and disease
    L. Fairbairn, R. Kapetanovic, D. P. Sester, and D. A. Hume
    J. Leukoc. Biol. 89, 855-871 (1 June 2011)

    The Inflammasomes in Kidney Disease
    H.-J. Anders, and D. A. Muruve
    J. Am. Soc. Nephrol. 22, 1007-1018 (1 June 2011)

    Genome-Wide Expression Profiling Identifies an Impairment of Negative Feedback Signals in the Crohn's Disease-Associated NOD2 Variant L1007fsinsC
    S. Billmann-Born, A. Till, A. Arlt, S. Lipinski, C. Sina, A. Latiano, V. Annese, R. Hasler, M. Kerick, T. Manke et al.
    J. Immunol. 186, 4027-4038 (1 April 2011)

    Intestinal epithelial cells as producers but not targets of chronic TNF suffice to cause murine Crohn-like pathology
    M. Roulis, M. Armaka, M. Manoloukos, M. Apostolaki, and G. Kollias
    Proc. Natl. Acad. Sci. USA 108, 5396-5401 (29 March 2011)

    Epithelial crosstalk at the microbiota-mucosal interface
    J. M. Wells, O. Rossi, M. Meijerink, and P. van Baarlen
    Proc. Natl. Acad. Sci. USA 108, 4607-4614 (15 March 2011)

    Intracellular Pathogen Sensor NOD2 Programs Macrophages to Trigger Notch1 Activation
    K. Bansal, and K. N. Balaji
    J Biol Chem 286, 5823-5835 (18 February 2011)

    Muramyl Dipeptide Synergizes with Staphylococcus aureus Lipoteichoic Acid To Recruit Neutrophils in the Mammary Gland and To Stimulate Mammary Epithelial Cells
    S. Bougarn, P. Cunha, A. Harmache, A. Fromageau, F. B. Gilbert, and P. Rainard
    CVI 17, 1797-1809 (1 November 2010)

    Colitis induced in mice with dextran sulfate sodium (DSS) is mediated by the NLRP3 inflammasome
    C. Bauer, P. Duewell, C. Mayer, H. A. Lehr, K. A. Fitzgerald, M. Dauer, J. Tschopp, S. Endres, E. Latz, M. Schnurr et al.
    Gut 59, 1192-1199 (1 September 2010)

    Induction and rescue of Nod2-dependent Th1-driven granulomatous inflammation of the ileum
    A. Biswas, Y.-J. Liu, L. Hao, A. Mizoguchi, N. H. Salzman, C. L. Bevins, and K. S. Kobayashi
    Proc. Natl. Acad. Sci. USA 107, 14739-14744 (17 August 2010)

    The Pathogen Recognition Receptor NOD2 Regulates Human FOXP3+ T Cell Survival
    M. K. Rahman, E. H. Midtling, P. A. Svingen, Y. Xiong, M. P. Bell, J. Tung, T. Smyrk, L. J. Egan, and W. A. Faubion
    J. Immunol. 184, 7247-7256 (15 June 2010)

    Regulation of innate immune responses by autophagy-related proteins
    T. Saitoh, and S. Akira
    JCB 189, 925-935 (14 June 2010)

    CARD15/NOD2 polymorphisms are associated with severe pulmonary sarcoidosis
    H. Sato, H. R. T. Williams, P. Spagnolo, A. Abdallah, T. Ahmad, T. R. Orchard, S. J. Copley, S. R. Desai, A. U. Wells, R. M. du Bois et al.
    Eur Respir J 35, 324-330 (1 February 2010)

    Nod2 regulates the host response towards microflora by modulating T cell function and epithelial permeability in mouse Peyer's patches
    F. Barreau, C. Madre, U. Meinzer, D. Berrebi, M. Dussaillant, F. Merlin, L. Eckmann, M. Karin, G. Sterkers, S. Bonacorsi et al.
    Gut 59, 207-217 (1 February 2010)

    How the Noninflammasome NLRs Function in the Innate Immune System
    J. P. Y. Ting, J. A. Duncan, and Y. Lei
    Science 327, 286-290 (15 January 2010)

    A role for Campylobacter jejuni-induced enteritis in inflammatory bowel disease?
    L. D. Kalischuk, and A. G. Buret
    Am. J. Physiol. Gastrointest. Liver Physiol. 298, G1-G9 (1 January 2010)

    NOD2 regulates hematopoietic cell function during graft-versus-host disease
    O. Penack, O. M. Smith, A. Cunningham-Bussel, X. Liu, U. Rao, N. Yim, I.-K. Na, A. M. Holland, A. Ghosh, S. X. Lu et al.
    JEM 206, 2101-2110 (28 September 2009)

    NLRP3/Cryopyrin Is Necessary for Interleukin-1{beta} (IL-1{beta}) Release in Response to Hyaluronan, an Endogenous Trigger of Inflammation in Response to Injury
    K. Yamasaki, J. Muto, K. R. Taylor, A. L. Cogen, D. Audish, J. Bertin, E. P. Grant, A. J. Coyle, A. Misaghi, H. M. Hoffman et al.
    J Biol Chem 284, 12762-12771 (8 May 2009)

    Blimp-1/PRDM1 Mediates Transcriptional Suppression of the NLR Gene NLRP12/Monarch-1
    C. A. Lord, D. Savitsky, R. Sitcheran, K. Calame, J. R. Wright, J. P.-Y. Ting, and K. L. Williams
    J. Immunol. 182, 2948-2958 (1 March 2009)

    The Innate Immune Receptor Nod1 Protects the Intestine from Inflammation-Induced Tumorigenesis
    G. Y. Chen, M. H. Shaw, G. Redondo, and G. Nunez
    Cancer Res. 68, 10060-10067 (15 December 2008)

    {beta}-PIX and Rac1 GTPase Mediate Trafficking and Negative Regulation of NOD2
    J. Eitel, M. Krull, A. C. Hocke, P. D. N'Guessan, J. Zahlten, B. Schmeck, H. Slevogt, S. Hippenstiel, N. Suttorp, B. Opitz et al.
    J. Immunol. 181, 2664-2671 (15 August 2008)

    Differential function of the NACHT-LRR (NLR) members Nod1 and Nod2 in arthritis
    L. A. B. Joosten, B. Heinhuis, S. Abdollahi-Roodsaz, G. Ferwerda, L. LeBourhis, D. J. Philpott, M.-A. Nahori, C. Popa, S. A. Morre, J. W. M. van der Meer et al.
    Proc. Natl. Acad. Sci. USA 105, 9017-9022 (1 July 2008)

    A NOD2-NALP1 complex mediates caspase-1-dependent IL-1{beta} secretion in response to Bacillus anthracis infection and muramyl dipeptide
    L.-C. Hsu, S. R. Ali, S. McGillivray, P.-H. Tseng, S. Mariathasan, E. W. Humke, L. Eckmann, J. J. Powell, V. Nizet, V. M. Dixit et al.
    Proc. Natl. Acad. Sci. USA 105, 7803-7808 (3 June 2008)

    Development of a Novel Noncompetitive Antagonist of IL-1 Receptor
    C. Quiniou, P. Sapieha, I. Lahaie, X. Hou, S. Brault, M. Beauchamp, M. Leduc, L. Rihakova, J.-S. Joyal, S. Nadeau et al.
    J. Immunol. 180, 6977-6987 (15 May 2008)

    Activation of Human NK Cells by the Bacterial Pathogen-Associated Molecular Pattern Muramyl Dipeptide
    V. Athie-Morales, G. M. O'Connor, and C. M. Gardiner
    J. Immunol. 180, 4082-4089 (15 March 2008)

    Pannexin-1-Mediated Intracellular Delivery of Muramyl Dipeptide Induces Caspase-1 Activation via Cryopyrin/NLRP3 Independently of Nod2
    N. Marina-Garcia, L. Franchi, Y.-G. Kim, D. Miller, C. McDonald, G.-J. Boons, and G. Nunez
    J. Immunol. 180, 4050-4057 (15 March 2008)

    Innate Immune Homeostasis by the Homeobox Gene Caudal and Commensal-Gut Mutualism in Drosophila
    J.-H. Ryu, S.-H. Kim, H.-Y. Lee, J. Y. Bai, Y.-D. Nam, J.-W. Bae, D. G. Lee, S. C. Shin, E.-M. Ha, W.-J. Lee et al.
    Science 319, 777-782 (8 February 2008)

    NLR proteins: integral members of innate immunity and mediators of inflammatory diseases
    J. M. Wilmanski, T. Petnicki-Ocwieja, and K. S. Kobayashi
    J. Leukoc. Biol. 83, 13-30 (1 January 2008)

    Chronic stimulation of Nod2 mediates tolerance to bacterial products
    M. Hedl, J. Li, J. H. Cho, and C. Abraham
    Proc. Natl. Acad. Sci. USA 104, 19440-19445 (4 December 2007)

    Low Dietary Calcium Levels Modulate Mucosal Caspase Expression and Increase Disease Activity in Mice with Dextran Sulfate Sodium Induced Colitis
    L. C. Pele, V. Thoree, F. Mustafa, S. He, L. Tsaprouni, N. A. Punchard, R. P. H. Thompson, S. M. Evans, and J. J. Powell
    J. Nutr. 137, 2475-2480 (1 November 2007)

    Single Nucleotide Polymorphisms in the NOD2/CARD15 Gene Are Associated With an Increased Risk of Relapse and Death for Patients With Acute Leukemia After Hematopoietic Stem-Cell Transplantation With Unrelated Donors
    N. P. Mayor, B. E. Shaw, D. A. Hughes, H. Maldonado-Torres, J. A. Madrigal, S. Keshav, and S. G.E. Marsh
    JCO 25, 4262-4269 (20 September 2007)

    MDP-induced interleukin-1{beta} processing requires Nod2 and CIAS1/NALP3
    Q. Pan, J. Mathison, C. Fearns, V. V. Kravchenko, J. Da Silva Correia, H. M. Hoffman, K. S. Kobayashi, J. Bertin, E. P. Grant, A. J. Coyle et al.
    J. Leukoc. Biol. 82, 177-183 (1 July 2007)

    Deubiquitinating enzyme CYLD negatively regulates the ubiquitin-dependent kinase Tak1 and prevents abnormal T cell responses
    W. W. Reiley, W. Jin, A. J. Lee, A. Wright, X. Wu, E. F. Tewalt, T. O. Leonard, C. C. Norbury, L. Fitzpatrick, M. Zhang et al.
    JEM 204, 1475-1485 (11 June 2007)

    The NOD2-RICK Complex Signals from the Plasma Membrane
    P. Lecine, S. Esmiol, J.-Y. Metais, C. Nicoletti, C. Nourry, C. McDonald, G. Nunez, J.-P. Hugot, J.-P. Borg, V. Ollendorff et al.
    J Biol Chem 282, 15197-15207 (18 May 2007)

    Modulation of Nod2-dependent NF-{kappa}B signaling by the actin cytoskeleton
    S. Legrand-Poels, G. Kustermans, F. Bex, E. Kremmer, T. A. Kufer, and J. Piette
    J. Cell Sci. 120, 1299-1310 (1 April 2007)

    The Role of Microbes in Crohn's Disease
    P. B. Eckburg, and D. A. Relman
    Clinical Infectious Diseases 44, 256-262 (15 January 2007)

    Pathogenesis of familial periodic fever syndromes or hereditary autoinflammatory syndromes
    A. Simon, and J. W. M. van der Meer
    Am. J. Physiol. Regul. Integr. Comp. Physiol. 292, R86-R98 (1 January 2007)

    A role for transcription factor NF-{kappa}B in autoimmunity: possible interactions of genes, sex, and the immune response
    E. Dale, M. Davis, and D. L. Faustman
    Adv. Physiol. Educ. 30, 152-158 (1 December 2006)

    Centaurin beta1 Down-regulates Nucleotide-binding Oligomerization Domains 1- and 2-dependent NF-{kappa}B Activation
    J. K. Yamamoto-Furusho, N. Barnich, R. Xavier, T. Hisamatsu, and D. K. Podolsky
    J Biol Chem 281, 36060-36070 (24 November 2006)

    Inhibition of Helicobacter hepaticus-Induced Colitis by IL-10 Requires the p50/p105 Subunit of NF-{kappa}B
    M. F. Tomczak, S. E. Erdman, A. Davidson, Y. Y. Wang, P. R. Nambiar, A. B. Rogers, B. Rickman, D. Luchetti, J. G. Fox, B. H. Horwitz et al.
    J. Immunol. 177, 7332-7339 (15 November 2006)

    Platelet-Activating Factor Receptor and Innate Immunity: Uptake of Gram-Positive Bacterial Cell Wall into Host Cells and Cell-Specific Pathophysiology
    S. Fillon, K. Soulis, S. Rajasekaran, H. Benedict-Hamilton, J. N. Radin, C. J. Orihuela, K. C. El Kasmi, G. Murti, D. Kaushal, M. W. Gaber et al.
    J. Immunol. 177, 6182-6191 (1 November 2006)

    Interleukin-23 drives innate and T cell-mediated intestinal inflammation
    S. Hue, P. Ahern, S. Buonocore, M. C. Kullberg, D. J. Cua, B. S. McKenzie, F. Powrie, and K. J. Maloy
    JEM 203, 2473-2483 (30 October 2006)

    Rescue of TRAF3-null mice by p100 NF-{kappa}B deficiency
    J. Q. He, B. Zarnegar, G. Oganesyan, S. K. Saha, S. Yamazaki, S. E. Doyle, P. W. Dempsey, and G. Cheng
    JEM 203, 2413-2418 (30 October 2006)

    The Inflammatory Caspases: Key Players in the Host Response to Pathogenic Invasion and Sepsis
    A. Nadiri, M. K. Wolinski, and M. Saleh
    J. Immunol. 177, 4239-4245 (1 October 2006)

    Nucleotide-Binding Oligomerization Domain-Like Receptors: Intracellular Pattern Recognition Molecules for Pathogen Detection and Host Defense
    L. Franchi, C. McDonald, T.-D. Kanneganti, A. Amer, and G. Nunez
    J. Immunol. 177, 3507-3513 (15 September 2006)

    Adherent and Invasive Escherichia coli Is Associated with Granulomatous Colitis in Boxer Dogs
    K. W. Simpson, B. Dogan, M. Rishniw, R. E. Goldstein, S. Klaessig, P. L. McDonough, A. J. German, R. M. Yates, D. G. Russell, S. E. Johnson et al.
    Infect. Immun. 74, 4778-4792 (1 August 2006)

    The gut flora as a forgotten organ
    A. M. O'Hara, and F. Shanahan
    EMBO Rep. 7, 688-693 (1 July 2006)

    IL-1{beta} Breaks Tolerance through Expansion of CD25+ Effector T Cells
    B. J. O'Sullivan, H. E. Thomas, S. Pai, P. Santamaria, Y. Iwakura, R. J. Steptoe, T. W. H. Kay, and R. Thomas
    J. Immunol. 176, 7278-7287 (15 June 2006)

    Dominant-negative TLR5 polymorphism reduces adaptive immune response to flagellin and negatively associates with Crohn's disease
    A. T. Gewirtz, M. Vijay-Kumar, S. R. Brant, R. H. Duerr, D. L. Nicolae, and J. H. Cho
    Am. J. Physiol. Gastrointest. Liver Physiol. 290, G1157-G1163 (1 June 2006)

    ASC Directs NF-{kappa}B Activation by Regulating Receptor Interacting Protein-2 (RIP2) Caspase-1 Interactions
    A. Sarkar, M. Duncan, J. Hart, E. Hertlein, D. C. Guttridge, and M. D. Wewers
    J. Immunol. 176, 4979-4986 (15 April 2006)

    Impaired dendritic cell function in Crohn's disease patients with NOD2 3020insC mutation
    M. Kramer, M. G. Netea, D. J. de Jong, B. J. Kullberg, and G. J. Adema
    J. Leukoc. Biol. 79, 860-866 (1 April 2006)

    Invited review: MDP and other muropeptides direct and synergistic effects on the immune system
    S. Traub, S. von Aulock, T. Hartung, and C. Hermann
    Innate Immunity 12, 69-85 (1 April 2006)

    Slipping the barrier: how variants in CARD15 could alter permeability of the intestinal wall and population health
    S Schreiber, S. von Aulock, T. Hartung, and C. Hermann
    Gut 55, 308-309 (1 March 2006)

    Layers of mutualism with commensal bacteria protect us from intestinal inflammation
    C Mueller, and A J Macpherson
    Gut 55, 276-284 (1 February 2006)

    Analysis of NOD2-mediated Proteome Response to Muramyl Dipeptide in HEK293 Cells
    D. Weichart, J. Gobom, S. Klopfleisch, R. Hasler, N. Gustavsson, S. Billmann, H. Lehrach, D. Seegert, S. Schreiber, P. Rosenstiel et al.
    J Biol Chem 281, 2380-2389 (27 January 2006)

    A Role for Erbin in the Regulation of Nod2-dependent NF-{kappa}B Signaling
    C. McDonald, F. F. Chen, V. Ollendorff, Y. Ogura, S. Marchetto, P. Lecine, J.-P. Borg, and G. Nunez
    J Biol Chem 280, 40301-40309 (2 December 2005)

    How Toll-like receptors and Nod-like receptors contribute to innate immunity in mammals
    J. H. Fritz, and S. E. Girardin
    Innate Immunity 11, 390-394 (1 December 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
    M. G. Netea, T. Azam, G. Ferwerda, S. E. Girardin, M. Walsh, J.-S. Park, E. Abraham, J.-M. Kim, D.-Y. Yoon, C. A. Dinarello et al.
    Proc. Natl. Acad. Sci. USA 102, 16309-16314 (8 November 2005)

    Synergy between TLR9 and NOD2 innate immune responses is lost in genetic Crohn's disease
    D A van Heel, S Ghosh, K A Hunt, C G Mathew, A Forbes, D P Jewell, and R J Playford
    Gut 54, 1553-1557 (1 November 2005)

    NOD2 regulation of Toll-like receptor responses and the pathogenesis of Crohn's disease
    T Watanabe, A Kitani, and W Strober
    Gut 54, 1515-1518 (1 November 2005)

    The Frameshift Mutation in Nod2 Results in Unresponsiveness Not Only to Nod2- but Also Nod1-activating Peptidoglycan Agonists
    M. G. Netea, G. Ferwerda, D. J. de Jong, C. Werts, I. G. Boneca, M. Jehanno, J. W. M. Van Der Meer, D. Mengin-Lecreulx, P. J. Sansonetti, D. J. Philpott et al.
    J Biol Chem 280, 35859-35867 (28 October 2005)

    DLG5 variants do not influence susceptibility to inflammatory bowel disease in the Scottish population
    C L Noble, E R Nimmo, H Drummond, L Smith, I D R Arnott, and J Satsangi
    Gut 54, 1416-1420 (1 October 2005)

    Mycobacterium avium subsp. paratuberculosis, Genetic Susceptibility to Crohn's Disease, and Sardinians: the Way Ahead
    L. A. Sechi, M. Gazouli, J. Ikonomopoulos, J. C. Lukas, A. M. Scanu, N. Ahmed, G. Fadda, and S. Zanetti
    J. Clin. Microbiol. 43, 5275-5277 (1 October 2005)

    Does innate immune response defect underlie inflammatory bowel disease in the Asian population?
    F Lanzarotto, A Akbar, and S Ghosh
    Postgrad. Med. J. 81, 483-485 (1 August 2005)

    E Cario, A Akbar, and S Ghosh
    Gut 54, 1182-1193 (1 August 2005)

    Membrane recruitment of NOD2 in intestinal epithelial cells is essential for nuclear factor-{kappa}B activation in muramyl dipeptide recognition
    N. Barnich, J. E. Aguirre, H.-C. Reinecker, R. Xavier, and D. K. Podolsky
    JCB 170, 21-26 (4 July 2005)

    Recognition of Staphylococcus aureus by the Innate Immune System
    B. Fournier, and D. J. Philpott
    Clin. Microbiol. Rev. 18, 521-540 (1 July 2005)

    GRIM-19 Interacts with Nucleotide Oligomerization Domain 2 and Serves as Downstream Effector of Anti-bacterial Function in Intestinal Epithelial Cells
    N. Barnich, T. Hisamatsu, J. E. Aguirre, R. Xavier, H.-C. Reinecker, and D. K. Podolsky
    J Biol Chem 280, 19021-19026 (13 May 2005)

    TLR Signaling in the Gut in Health and Disease
    M. T. Abreu, M. Fukata, and M. Arditi
    J. Immunol. 174, 4453-4460 (15 April 2005)

    Immunity, Inflammation, and Allergy in the Gut
    T. T. MacDonald, and G. Monteleone
    Science 307, 1920-1925 (25 March 2005)

    A Nod toward understanding Crohn's disease
    D. Secko, and G. Monteleone
    CMAJ 172, 738-739 (15 March 2005)

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