Table of Contents Author Guidelines Submit a Manuscript
International Journal of Inflammation
Volume 2010, Article ID 671258, 12 pages
http://dx.doi.org/10.4061/2010/671258
Review Article

Microbial Sensing by the Intestinal Epithelium in the Pathogenesis of Inflammatory Bowel Disease

Division of Gastroenterology and Hepatology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland

Received 19 April 2010; Accepted 17 May 2010

Academic Editor: Dirk Haller

Copyright © 2010 Michael Scharl and Gerhard Rogler. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. T. Jess, L. Riis, and L. Riis, “Disease concordance, zygosity, and NOD2/CARD15 status: follow-up of a population-based cohort of Danish twins with inflammatory bowel disease,” American Journal of Gastroenterology, vol. 100, no. 11, pp. 2486–2492, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  2. C. Abraham and J. H. Cho, “Bugging of the intestinal mucosa,” The New England Journal of Medicine, vol. 357, no. 7, pp. 708–710, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  3. N. Sakamoto, S. Kono, and S. Kono, “Dietary risk factors for inflammatory bowel disease: a multicenter case-control study in Japan,” Inflammatory Bowel Diseases, vol. 11, no. 2, pp. 154–163, 2005. View at Publisher · View at Google Scholar · View at Scopus
  4. S. Reif, I. Klein, F. Lubin, M. Farbstein, A. Hallak, and T. Gilat, “Pre-illness dietary factors in inflammatory bowel disease,” Gut, vol. 40, no. 6, pp. 754–760, 1997. View at Google Scholar · View at Scopus
  5. A. Tragnone, D. Valpiani, F. Miglio, G. Elmi, G. Bazzocchi, E. Pipitone, and G. A. Lanfranchi, “Dietary habits as risk factors for inflammatory bowel disease,” European Journal of Gastroenterology and Hepatology, vol. 7, no. 1, pp. 47–51, 1995. View at Google Scholar
  6. O. Sandu, K. Song, W. Cai, F. Zheng, J. Uribarri, and H. Vlassara, “Insulin resistance and type 2 diabetes in high-fat-fed mice are linked to high glycotoxin intake,” Diabetes, vol. 54, no. 8, pp. 2314–2319, 2005. View at Publisher · View at Google Scholar · View at Scopus
  7. D. Cai, M. Yuan, D. F. Frantz, P. A. Melendez, L. Hansen, J. Lee, and S. E. Shoelson, “Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-κB,” Nature Medicine, vol. 11, no. 2, pp. 183–190, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  8. R. Shoda, K. Matsueda, S. Yamato, and N. Umeda, “Epidemiologic analysis of Crohn disease in Japan: increased dietary intake of n-6 polyunsaturated fatty acids and animal protein relates to the increased incidence of Crohn's disease in Japan,” American Journal of Clinical Nutrition, vol. 63, no. 5, pp. 741–745, 1996. View at Google Scholar · View at Scopus
  9. A. Gil, “Polyunsaturated fatty acids and inflammatory diseases,” Biomedicine and Pharmacotherapy, vol. 56, no. 8, pp. 388–396, 2002. View at Publisher · View at Google Scholar · View at Scopus
  10. A. R. Hart, R. Luben, and R. Luben, “Diet in the aetiology of ulcerative colitis: a European prospective cohort study,” Digestion, vol. 77, no. 1, pp. 57–64, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  11. D. N. Frank, A. L. S. Amand, R. A. Feldman, E. C. Boedeker, N. Harpaz, and N. R. Pace, “Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 34, pp. 13780–13785, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  12. C. Manichanh, L. Rigottier-Gois, and L. Rigottier-Gois, “Reduced diversity of faecal microbiota in Crohn's disease revealed by a metagenomic approach,” Gut, vol. 55, no. 2, pp. 205–211, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  13. S. J. Ott, M. Musfeldt, and M. Musfeldt, “Reduction in diversity of the colonic mucosa associated bacterial microflora in patients with active inflammatory bowel disease,” Gut, vol. 53, no. 5, pp. 685–693, 2004. View at Publisher · View at Google Scholar · View at Scopus
  14. M. Baumgart, B. Dogan, and B. Dogan, “Culture independent analysis of ileal mucosa reveals a selective increase in invasive Escherichia coli novel phylogeny relative to depletion of Clostridiales in Crohn's disease involving the ileum,” The ISME Journal, vol. 1, no. 5, pp. 403–418, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  15. M. Martinez-Medina, X. Aldeguer, F. Gonzalez-Huix, D. Acero, and L. J. Garcia-Gil, “Abnormal microbiota composition in the ileocolonic mucosa of Crohn's disease patients as revealed by polymerase chain reaction-denaturing gradient gel electrophoresis,” Inflammatory Bowel Diseases, vol. 12, no. 12, pp. 1136–1145, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  16. H. C. Rath, M. Schultz, and M. Schultz, “Different subsets of enteric bacteria induce and perpetuate experimental colitis in rats and mice,” Infection and Immunity, vol. 69, no. 4, pp. 2277–2285, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  17. C. Veltkamp, S. L. Tonkonogy, and S. L. Tonkonogy, “Continuous stimulation by normal luminal bacteria is essential for the development and perpetuation of colitis in Tgε26 mice,” Gastroenterology, vol. 120, no. 4, pp. 900–913, 2001. View at Google Scholar · View at Scopus
  18. M. Schultz, S. L. Tonkonogy, and S. L. Tonkonogy, “IL-2-deficient mice raised under germfree conditions develop delayed mild focal intestinal inflammation,” American Journal of Physiology, vol. 276, no. 6, pp. G1461–G1472, 1999. View at Google Scholar · View at Scopus
  19. R. K. Sellon, S. Tonkonogy, and S. Tonkonogy, “Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice,” Infection and Immunity, vol. 66, no. 11, pp. 5224–5231, 1998. View at Google Scholar · View at Scopus
  20. H. C. Rath, K. H. Wilson, and R. B. Sartor, “Differential induction of colitis and gastritis in HLA-B27 transgenic rats selectively colonized with Bacteroides vulgatus or Escherichia coli,” Infection and Immunity, vol. 67, no. 6, pp. 2969–2974, 1999. View at Google Scholar · View at Scopus
  21. H. C. Rath, J. S. Ikeda, H.-J. Linde, J. Scholmerich, K. H. Wilson, and R. Balfour Sartor, “Varying cecal bacterial loads influences colitis and gastritis in HLA- B27 transgenic rats,” Gastroenterology, vol. 116, no. 2, pp. 310–319, 1999. View at Publisher · View at Google Scholar · View at Scopus
  22. R. B. Sartor, “The influence of normal microbial flora on the development of chronic mucosal inflammation,” Research in Immunology, vol. 148, no. 8-9, pp. 567–576, 1997. View at Publisher · View at Google Scholar · View at Scopus
  23. H. C. Rath, H. H. Herfarth, and H. H. Herfarth, “Normal luminal bacteria, especially bacteroides species, mediate chronic colitis, gastritis, and arthritis in HLA-B27/human β2 microglobulin transgenic rats,” Journal of Clinical Investigation, vol. 98, no. 4, pp. 945–953, 1996. View at Google Scholar · View at Scopus
  24. Q. Yuan and W. A. Walker, “Innate immunity of the gut: mucosal defense in health and disease,” Journal of Pediatric Gastroenterology and Nutrition, vol. 38, no. 5, pp. 463–473, 2004. View at Google Scholar · View at Scopus
  25. H. Zhang, D. Massey, M. Tremelling, and M. Parkes, “Genetics of inflammatory bowel disease: clues to pathogenesis,” British Medical Bulletin, vol. 87, no. 1, pp. 17–30, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  26. A. C. Ferreira, S. Almeida, and S. Almeida, “NOD2/CARD15 and TNFA, but not IL1B and IL1RN, are associated with Crohn's disease,” Inflammatory Bowel Diseases, vol. 11, no. 4, pp. 331–339, 2005. View at Google Scholar
  27. H. Sashio, K. Tamura, and K. Tamura, “Polymorphisms of the TNF gene and the TNF receptor superfamily member 1B gene are associated with susceptibility to ulcerative colitis and Crohn's disease, respectively,” Immunogenetics, vol. 53, no. 12, pp. 1020–1027, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  28. S. A. Fisher, M. Tremelling, and M. Tremelling, “Genetic determinants of ulcerative colitis include the ECM1 locus and five loci implicated in Crohn's disease,” Nature Genetics, vol. 40, no. 6, pp. 710–712, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  29. P. R. Burton, D. G. Clayton, and D. G. Clayton, “Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls,” Nature, vol. 447, no. 7145, pp. 661–678, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  30. J.-P. Hugot, M. Chamaillard, and M. Chamaillard, “Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease,” Nature, vol. 411, no. 6837, pp. 599–603, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  31. Y. Ogura, D. K. Bonen, and D. K. Bonen, “A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease,” Nature, vol. 411, no. 6837, pp. 603–606, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  32. D. Franchimont, S. Vermeire, and S. Vermeire, “Deficient host-bacteria interactions in inflammatory bowel disease? the toll-like receptor (TLR)-4 Asp299gly polymorphism is associated with Crohn's disease and ulcerative colitis,” Gut, vol. 53, no. 7, pp. 987–992, 2004. View at Publisher · View at Google Scholar · View at Scopus
  33. L. E. Oostenbrug, J. P. H. Drenth, and J. P. H. Drenth, “Association between Toll-like receptor 4 and inflammatory bowel disease,” Inflammatory Bowel Diseases, vol. 11, no. 6, pp. 567–575, 2005. View at Publisher · View at Google Scholar · View at Scopus
  34. D. C. O. Massey and M. Parkes, “Genome-wide association scanning highlights two autophagy genes, ATG16L1 and IRGM, as being significantly associated with Crohn's disease,” Autophagy, vol. 3, no. 6, pp. 649–651, 2007. View at Google Scholar · View at Scopus
  35. R. K. Weersma, P. C. F. Stokkers, and P. C. F. Stokkers, “Confirmation of multiple Crohn's disease susceptibility loci in a large Dutch-Belgian cohort,” American Journal of Gastroenterology, vol. 104, no. 3, pp. 630–638, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  36. A. Franke, T. Balschun, and T. Balschun, “Replication of signals from recent studies of Crohn's disease identifies previously unknown disease loci for ulcerative colitis,” Nature Genetics, vol. 40, no. 6, pp. 713–715, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  37. K. Sugawara, T. S. Olson, and T. S. Olson, “Linkage to peroxisome proliferator-activated receptor-γ in SAMP1/YitFc mice and in human Crohn's disease,” Gastroenterology, vol. 128, no. 2, pp. 351–360, 2005. View at Publisher · View at Google Scholar · View at Scopus
  38. S. R. Brant, C. I. M. Panhuysen, and C. I. M. Panhuysen, “MDR1 Ala893 Polymorphism Is Associated with Inflammatory Bowel Disease,” American Journal of Human Genetics, vol. 73, no. 6, pp. 1282–1292, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  39. M. Schwab, E. Schaeffeler, and E. Schaeffeler, “Association between the C3435T MDR1 gene polymorphism and susceptibility for ulcerative colitis,” Gastroenterology, vol. 124, no. 1, pp. 26–33, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  40. V. D. Peltekova, R. F. Wintle, and R. F. Wintle, “Functional variants of OCTN cation transporter genes are associated with Crohn disease,” Nature Genetics, vol. 36, no. 5, pp. 471–475, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  41. S. Waller, M. Tremelling, F. Bredin, L. Godfrey, J. Howson, and M. Parkes, “Evidence for association of OCTN genes and IBD5 with ulcerative colitis,” Gut, vol. 55, no. 6, pp. 809–814, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  42. E. Cario and D. K. Podolsky, “Intestinal epithelial Tollerance versus inTollerance of commensals,” Molecular Immunology, vol. 42, no. 8, pp. 887–893, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  43. M. Hausmann, S. Kiessling, and S. Kiessling, “Toll-like receptors 2 and 4 are up-regulated during intestinal inflammation,” Gastroenterology, vol. 122, no. 7, pp. 1987–2000, 2002. View at Google Scholar · View at Scopus
  44. P. D. Smith, L. E. Smythies, and L. E. Smythies, “Intestinal macrophages lack CD14 and CD89 and consequently are down-regulated for LPS- and IgA-mediated activities,” Journal of Immunology, vol. 167, no. 5, pp. 2651–2656, 2001. View at Google Scholar · View at Scopus
  45. E. Cario and D. K. Podolsky, “Differential alteration in intestinal epithelial cell expression of Toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease,” in Infection and Immunity, vol. 68, no. 12, pp. 7010–7017, 2000. View at Publisher · View at Google Scholar · View at Scopus
  46. Y. Ogura, N. Inohara, A. Benito, F. F. Chen, S. Yamaoka, and G. Núñez, “Nod2, a Nod1/Apaf-1 family member that is restricted to monocytes and activates NF-κB,” The Journal of Biological Chemistry, vol. 276, no. 7, pp. 4812–4818, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  47. S. Rakoff-Nahoum, J. Paglino, F. Eslami-Varzaneh, S. Edberg, and R. Medzhitov, “Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis,” Cell, vol. 118, no. 2, pp. 229–241, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  48. M. E. H. Bashir, S. Louie, H. N. Shi, and C. Nagler-Anderson, “Toll-like receptor 4 signaling by intestinal microbes influences susceptibility to food allergy,” Journal of Immunology, vol. 172, no. 11, pp. 6978–6987, 2004. View at Google Scholar · View at Scopus
  49. M. Gazouli, G. Mantzaris, and G. Mantzaris, “Association between polymorphisms in the Toll-like receptor 4, CD14, and CARD15/NOD2 and inflammatory bowel disease in the Greek population,” World Journal of Gastroenterology, vol. 11, no. 5, pp. 681–685, 2005. View at Google Scholar · View at Scopus
  50. J.-H. Lee, B. Lee, and B. Lee, “Lactobacillus suntoryeus inhibits pro-inflammatory cytokine expression and TLR-4-linked NF-κB activation in experimental colitis,” International Journal of Colorectal Disease, vol. 24, no. 2, pp. 231–237, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  51. L. Dubuquoy, E. A. Jansson, and E. A. Jansson, “Impaired expression of peroxisome proliferator-activated receptor γ in ulcerative colitis,” Gastroenterology, vol. 124, no. 5, pp. 1265–1276, 2003. View at Publisher · View at Google Scholar · View at Scopus
  52. D. Kelly, J. I. Campbell, and J. I. Campbell, “Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmic shutting of PPAR-γ and ReIA,” Nature Immunology, vol. 5, no. 1, pp. 104–112, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  53. C. O. Elson, R. B. Sartor, G. S. Tennyson, and R. H. Riddell, “Experimental models of inflammatory bowel disease,” Gastroenterology, vol. 109, no. 4, pp. 1344–1367, 1995. View at Publisher · View at Google Scholar · View at Scopus
  54. M. Kobayashi, M.-N. Kweon, H. Kuwata, R. D. Schreiber, H. Kiyono, K. Takeda, and S. Akira, “Toll-like receptor-dependent production of IL-12p40 causes chronic enterocolitis in myeloid cell-specific Stat3-deficient mice,” Journal of Clinical Investigation, vol. 111, no. 9, pp. 1297–1308, 2003. View at Publisher · View at Google Scholar · View at Scopus
  55. F. Martinon, X. Chen, A.-H. Lee, and L. H. Glimcher, “TLR activation of the transcription factor XBP1 regulates innate immune responses in macrophages,” Nature Immunology, vol. 11, no. 5, pp. 411–418, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  56. A. Kaser, A.-H. Lee, and A.-H. Lee, “XBP1 Links ER Stress to Intestinal Inflammation and Confers Genetic Risk for Human Inflammatory Bowel Disease,” Cell, vol. 134, no. 5, pp. 743–756, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  57. A. Shkoda, P. A. Ruiz, H. Daniel, S. C. Kim, G. Rogler, R. B. Sartor, and D. Haller, “Interleukin-10 blocked endoplasmatic reticulum stress in intestinal epithelial cells: impact on chronic inflammation,” Gastroenterology, vol. 132, no. 1, pp. 190–207, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  58. C. K. Heazlewood, M. C. Cook, and M. C. Cook, “Aberrant mucin assembly in mice causes endoplasmic reticulum stress and spontaneous inflammation resembling ulcerative colitis,” PLoS Medicine, vol. 5, no. 3, pp. 440–460, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  59. S. E. Girardin, I. G. Boneca, and I. G. Boneca, “Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection,” The Journal of Biological Chemistry, vol. 278, no. 11, pp. 8869–8872, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  60. N. Inohara, Y. Ogura, and Y. Ogura, “Host recognition of bacterial muramyl dipeptide mediated through NOD2: implications for Crohn's disease,” The Journal of Biological Chemistry, vol. 278, no. 8, pp. 5509–5512, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  61. S. R. Vavricka, M. W. Musch, and M. W. Musch, “hPepT1 transports muramyl dipeptide, activating NF-κB and stimulating IL-8 secretion in human colonic Caco2/bbe cells,” Gastroenterology, vol. 127, no. 5, pp. 1401–1409, 2004. View at Publisher · View at Google Scholar · View at Scopus
  62. T. Hisamatsu, M. Suzuki, H.-C. Reinecker, W. J. Nadeau, B. A. McCormick, and D. K. Podolsky, “CARD15/NOD2 functions as an antibacterial factor in human intestinal epithelial cells,” Gastroenterology, vol. 124, no. 4, pp. 993–1000, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  63. E. Voss, J. Wehkamp, K. Wehkamp, E. F. Stange, J. M. Schröder, and J. Harder, “NOD2/CARD15 mediates induction of the antimicrobial peptide human beta-defensin-2,” The Journal of Biological Chemistry, vol. 281, no. 4, pp. 2005–2011, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  64. J. Wehkamp, J. Harder, and J. Harder, “NOD2 (CARD15) mutations in Crohn's disease are associated with diminished mucosal α-defensin expression,” Gut, vol. 53, no. 11, pp. 1658–1664, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  65. P. Rosenstiel, M. Fantini, K. Bräutigam, T. Kühbacher, G. H. Waetzig, D. Seegert, and S. Schreiber, “TNF-α and IFN-γ regulate the expression of the NOD2 (CARD15) gene in human intestinal epithelial cells,” Gastroenterology, vol. 124, no. 4, pp. 1001–1009, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  66. A. P. Cuthbert, S. A. Fisher, and S. A. Fisher, “The contribution of NOD2 gene mutations to the risk and site of disease in inflammatory bowel disease,” Gastroenterology, vol. 122, no. 4, pp. 867–874, 2002. View at Google Scholar · View at Scopus
  67. S. Lesage, H. Zouali, and H. Zouali, “CARD15/NOD2 mutational analysis and genotype-phenotype correlation in 612 patients with inflammatory bowel disease,” American Journal of Human Genetics, vol. 70, no. 4, pp. 845–857, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  68. S. Maeda, L.-C. Hsu, and L.-C. Hsu, “Nod2 mutation in Crohn's disease potentiates NF-κB activity and IL-1β processing,” Science, vol. 307, no. 5710, pp. 734–738, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  69. A. Swidsinski, A. Ladhoff, and A. Ladhoff, “Mucosal flora in inflammatory bowel disease,” Gastroenterology, vol. 122, no. 1, pp. 44–54, 2002. View at Google Scholar · View at Scopus
  70. E. Holler, G. Rogler, and G. Rogler, “Prognostic significance of NOD2/CARD15 variants in HLA-identical sibling hematopoietic stem cell transplantation: effect on long-term outcome is confirmed in 2 independent cohorts and may be modulated by the type of gastrointestinal decontamination,” Blood, vol. 107, no. 10, pp. 4189–4193, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  71. E. Holler, G. Rogler, and G. Rogler, “Both donor and recipient NOD2/CARD15 mutations associate with transplant-related mortality and GvHD following allogeneic stem cell transplantation,” Blood, vol. 104, no. 3, pp. 889–894, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  72. E. Holler, G. Rogler, and G. Rogler, “The role of genetic variants of NOD2/CARD15, a receptor of the innate immune system, in GvHD and complications following related and unrelated donor haematopoietic stem cell transplantation,” International Journal of Immunogenetics, vol. 35, no. 4-5, pp. 381–384, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  73. A. H. Elmaagacli, M. Koldehoff, and M. Koldehoff, “Mutations in innate immune system NOD2/CARD 15 and TLR-4 (Thr399Ile) genes influence the risk for severe acute graft-versus-host disease in patients who underwent an allogeneic transplantation,” Transplantation, vol. 81, no. 2, pp. 247–254, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  74. O. Penack, O. M. Smith, and O. M. Smith, “NOD2 regulates hematopoietic cell function during graft-versus-host disease,” The Journal of Experimental Medicine, vol. 206, no. 10, pp. 2101–2110, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  75. W. J. F. M. Van der Velden, N. M. A. Blijlevens, and N. M. A. Blijlevens, “NOD2 polymorphisms predict severe acute graft-versus-host and treatment-related mortality in T-cell-depleted haematopoietic stem cell transplantation,” Bone Marrow Transplantation, vol. 44, no. 4, pp. 243–248, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  76. D. E. Jones and C. L. Bevins, “Paneth cells of the human small intestine express an antimicrobial peptide gene,” The Journal of Biological Chemistry, vol. 267, no. 32, pp. 23216–23225, 1992. View at Google Scholar · View at Scopus
  77. K. Fellermann, J. Wehkamp, K. R. Herrlinger, and E. F. Stange, “Crohn's disease: a defensin deficiency syndrome?” European Journal of Gastroenterology and Hepatology, vol. 15, no. 6, pp. 627–634, 2003. View at Publisher · View at Google Scholar · View at Scopus
  78. R. N. Cunliffe, “α-defensins in the gastrointestinal tract,” Molecular Immunology, vol. 40, no. 7, pp. 463–467, 2003. View at Publisher · View at Google Scholar · View at Scopus
  79. J. Wehkamp, M. Schmid, and E. F. Stange, “Defensins and other antimicrobial peptides in inflammatory bowel disease,” Current Opinion in Gastroenterology, vol. 23, no. 4, pp. 370–378, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  80. J. Wehkamp, H. Chu, B. Shen, R. W. Feathers, R. J. Kays, S. K. Lee, and C. L. Bevins, “Paneth cell antimicrobial peptides: topographical distribution and quantification in human gastrointestinal tissues,” FEBS Letters, vol. 580, no. 22, pp. 5344–5350, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  81. J. Wehkamp, N. H. Salzman, and N. H. Salzman, “Reduced Paneth cell α-defensins in ileal Crohn's disease,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 50, pp. 18129–18134, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  82. M. C. Grimm and P. Pavli, “NOD2 mutations and Crohn's disease: are Paneth cells and their antimicrobial peptides the link?” Gut, vol. 53, no. 11, pp. 1558–1560, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  83. L. Agostini, F. Martinon, K. Burns, M. F. McDermott, P. N. Hawkins, and J. Tschopp, “NALP3 forms an IL-1β-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder,” Immunity, vol. 20, no. 3, pp. 319–325, 2004. View at Publisher · View at Google Scholar · View at Scopus
  84. T. Ghayur, S. Banerjee, and S. Banerjee, “Caspase-1 processes IFN-γ-inducing factor and regulates LPS-induced IFN-γ production,” Nature, vol. 386, no. 6625, pp. 619–623, 1997. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  85. Y. Gu, K. Kuida, and K. Kuida, “Activation of interferon-γ inducing factor mediated by interleukin-1β converting enzyme,” Science, vol. 275, no. 5297, pp. 206–209, 1997. View at Publisher · View at Google Scholar · View at Scopus
  86. K. Kuida, J. A. Lippke, G. Ku, M. W. Harding, D. J. Livingston, M. S.-S. Su, and R. A. Flavell, “Altered cytokine export and apoptosis in mice deficient in interleukin-1β converting enzyme,” Science, vol. 267, no. 5206, pp. 2000–2003, 1995. View at Google Scholar · View at Scopus
  87. S. C. Eisenbarth, O. R. Colegio, W. O'Connor Jr., F. S. Sutterwala, and R. A. Flavell, “Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants,” Nature, vol. 453, no. 7198, pp. 1122–1126, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  88. V. Hornung, F. Bauernfeind, and F. Bauernfeind, “Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization,” Nature Immunology, vol. 9, no. 8, pp. 847–856, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  89. M. Kool, V. Pétrilli, and V. Pétrilli, “Cutting edge: alum adjuvant stimulates inflammatory dendritic cells through activation of the NALP3 inflammasome,” Journal of Immunology, vol. 181, no. 6, pp. 3755–3759, 2008. View at Google Scholar · View at Scopus
  90. H. Li, S. B. Willingham, J. P.-Y. Ting, and F. Re, “Cutting edge: inflammasome activation by alum and alum's adjuvant effect are mediated by NLRP3,” Journal of Immunology, vol. 181, no. 1, pp. 17–21, 2008. View at Google Scholar · View at Scopus
  91. S. Mariathasan, D. S. Weiss, and D. S. Weiss, “Cryopyrin activates the inflammasome in response to toxins and ATP,” Nature, vol. 440, no. 7081, pp. 228–232, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  92. N. Özören, J. Masumoto, and J. Masumoto, “Distinct roles of TLR2 and the adaptor ASC in IL-1β/IL-18 secretion in response to Listeria monocytogenes,” Journal of Immunology, vol. 176, no. 7, pp. 4337–4342, 2006. View at Google Scholar · View at Scopus
  93. F. Martinon, L. Agostini, E. Meylan, and J. Tschopp, “Identification of bacterial muramyl dipeptide as activator of the NALP3/Cryopyrin inflammasome,” Current Biology, vol. 14, no. 21, pp. 1929–1934, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  94. F. Martinon and J. Tschopp, “NLRs join TLRs as innate sensors of pathogens,” Trends in Immunology, vol. 26, no. 8, pp. 447–454, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  95. Q. Pan, J. Mathison, and J. Mathison, “MDP-induced interleukin-1β processing requires Nod2 and CIAS1/NALP3,” Journal of Leukocyte Biology, vol. 82, no. 1, pp. 177–183, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  96. M. Kramer, M. G. Netea, D. J. De Jong, B. J. Kullberg, and G. J. Adema, “Impaired dendritic cell function in Crohn's disease patients with NOD2 3020insC mutation,” Journal of Leukocyte Biology, vol. 79, no. 4, pp. 860–866, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  97. D. A. Van Heel, S. Ghosh, and S. Ghosh, “Muramyl dipeptide and toll-like receptor sensitivity in NOD2-associated Crohn's disease,” The Lancet, vol. 365, no. 9473, pp. 1794–1796, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  98. J.-M. Bruey, N. Bruey-Sedano, and N. Bruey-Sedano, “Bcl-2 and Bcl-XL regulate proinflammatory caspase-1 activation by interaction with NALP1,” Cell, vol. 129, no. 1, pp. 45–56, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  99. B. Faustin, L. Lartigue, and L. Lartigue, “Reconstituted NALP1 inflammasome reveals two-step mechanism of caspase-1 activation,” Molecular Cell, vol. 25, no. 5, pp. 713–724, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  100. B. Levine and V. Deretic, “Unveiling the roles of autophagy in innate and adaptive immunity,” Nature Reviews Immunology, vol. 7, no. 10, pp. 767–777, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  101. M. Parkes, J. C. Barrett, and J. C. Barrett, “Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility,” Nature Genetics, vol. 39, no. 7, pp. 830–832, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  102. J. Hampe, A. Franke, and A. Franke, “A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1,” Nature Genetics, vol. 39, no. 2, pp. 207–211, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  103. N. Barnich, F. A. Carvalho, and F. A. Carvalho, “CEACAM6 acts as a receptor for adherent-invasive E. coli, supporting ileal mucosa colonization in Crohn disease,” Journal of Clinical Investigation, vol. 117, no. 6, pp. 1566–1574, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  104. A. Darfeuille-Michaud, J. Boudeau, and J. Boudeau, “High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn's disease,” Gastroenterology, vol. 127, no. 2, pp. 412–421, 2004. View at Publisher · View at Google Scholar · View at Scopus
  105. A.-L. Glasser, J. Boudeau, N. Barnich, M.-H. Perruchot, J.-F. Colombel, and A. Darfeuille-Michaud, “Adherent invasive Escherichia coli strains from patients with Crohn's disease survive and replicate within macrophages without inducing host cell death,” Infection and Immunity, vol. 69, no. 9, pp. 5529–5537, 2001. View at Publisher · View at Google Scholar · View at Scopus
  106. P. Lapaquette, A.-L. Glasser, A. Huett, R. J. Xavier, and A. Darfeuille-Michaud, “Crohn's disease-associated adherent-invasive E. coli are selectively favoured by impaired autophagy to replicate intracellularly,” Cellular Microbiology, vol. 12, no. 1, pp. 99–113, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  107. C. L. Birmingham, A. C. Smith, M. A. Bakowski, T. Yoshimori, and J. H. Brumell, “Autophagy controls Salmonellainfection in response to damage to the Salmonella-containing vacuole,” The Journal of Biological Chemistry, vol. 281, no. 16, pp. 11374–11383, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  108. P. Kuballa, A. Huett, J. D. Rioux, M. J. Daly, and R. J. Xavier, “Impaired autophagy of an intracellular pathogen induced by a Crohn's disease associated ATG16L1 variant,” PLoS ONE, vol. 3, no. 10, article e3391, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  109. K. Cadwell, J. Y. Liu, and J. Y. Liu, “A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells,” Nature, vol. 456, no. 7219, pp. 259–263, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  110. T. Saitoh, N. Fujita, and N. Fujita, “Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1β production,” Nature, vol. 456, no. 7219, pp. 264–268, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  111. R. Cooney, J. Baker, and J. Baker, “NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation,” Nature Medicine, vol. 16, pp. 90–97, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  112. L. H. Travassos, L. A. M. Carneiro, and L. A. M. Carneiro, “Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry,” Nature Immunology, vol. 11, pp. 55–62, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  113. J. Ten Hoeve, M. D. J. Ibarra-Sanchez, Y. Fu, W. Zhu, M. Tremblay, M. David, and K. Shuai, “Identification of a nuclear Stat1 protein tyrosine phosphatase,” Molecular and Cellular Biology, vol. 22, no. 16, pp. 5662–5668, 2002. View at Publisher · View at Google Scholar · View at Scopus
  114. T. Yamamoto, Y. Sekine, K. Kashima, A. Kubota, N. Sato, N. Aoki, and T. Matsuda, “The nuclear isoform of protein-tyrosine phosphatase TC-PTP regulates interleukin-6-mediated signaling pathway through STAT3 dephosphorylation,” Biochemical and Biophysical Research Communications, vol. 297, no. 4, pp. 811–817, 2002. View at Publisher · View at Google Scholar · View at Scopus
  115. W. Zhu, T. Mustelin, and M. David, “Arginine methylation of STAT1 regulates its dephosphorylation by T cell protein tyrosine phosphatase,” The Journal of Biological Chemistry, vol. 277, no. 39, pp. 35787–35790, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  116. C. Van Vliet, P. E. Bukczynska, M. A. Puryer, C. M. Sadek, B. J. Shields, M. L. Tremblay, and T. Tiganis, “Selective regulation of tumor necrosis factor-induced Erk signaling by Src family kinases and the T cell protein tyrosine phosphatase,” Nature Immunology, vol. 6, no. 3, pp. 253–260, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  117. E. Matilla, T. Pellinen, J. Nevo, K. Vuoriluoto, A. Arjonen, and J. Ivaska, “Negative regulation of EGFR signalling through integrin-α1β1-mediated activation of protein tyrosine phosphatase TCPTP,” Nature Cell Biology, vol. 7, no. 1, pp. 78–85, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  118. T. Tiganis, A. M. Bennett, K. S. Ravichandran, and N. K. Tonks, “Epidermal growth factor receptor and the adaptor protein p52(Shc) are specific substrates of T-cell protein tyrosine phosphatase,” Molecular and Cellular Biology, vol. 18, no. 3, pp. 1622–1634, 1998. View at Google Scholar · View at Scopus
  119. S. Galic, M. Klingler-Hoffmann, M. T. Fodero-Tavoletti, M. A. Puryer, T.-C. Meng, N. K. Tonks, and T. Tiganis, “Regulation of insulin receptor signaling by the protein tyrosine phosphatase TCPTP,” Molecular and Cellular Biology, vol. 23, no. 6, pp. 2096–2108, 2003. View at Publisher · View at Google Scholar · View at Scopus
  120. K. M. Heinonen, F. P. Nestel, E. W. Newell, G. Charette, T. A. Seemayer, M. L. Tremblay, and W. S. Lapp, “T-cell protein tyrosine phosphatase deletion results in progressive systemic inflammatory disease,” Blood, vol. 103, no. 9, pp. 3457–3464, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  121. K. E. You-Ten, E. S. Muise, and E. S. Muise, “Impaired bone marrow microenvironment and immune function in T cell protein tyrosine phosphatase-deficient mice,” Journal of Experimental Medicine, vol. 186, no. 5, pp. 683–693, 1997. View at Publisher · View at Google Scholar · View at Scopus
  122. M. Dupuis, M. D. J. Ibarra-Sánchez, M. L. Tremblay, and P. Duplay, “Gr-1+ myeloid cells lacking T cell protein tyrosine phosphatase inhibit lymphocyte proliferation by an IFN-γ- and nitric oxide-dependent mechanism,” Journal of Immunology, vol. 171, no. 2, pp. 726–732, 2003. View at Google Scholar · View at Scopus
  123. M. Scharl, G. Paul, and G. Paul, “Protection of epithelial barrier function by the Crohn’s disease associated gene, protein tyrosine phosphatase N2,” Gastroenterology, vol. 137, no. 6, pp. 2030–2040, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus