TLR signaling in the gut in health and disease

Journal of Immunology

Volumn 174, Issue 8, 2005, Pages 4453-4460

  Abreu, Maria T ^a   Fukata, Masayuki ^a   Arditi, Moshe ^b  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^b BURNS AND ALLEN RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIGEN; BACTERIUM LIPOPOLYSACCHARIDE; CASPASE RECRUITMENT DOMAIN PROTEIN 15; DEFENSIN; LIPOPEPTIDE; LIPOTEICHOIC ACID; NUCLEOTIDE OLIGOMERIZATION DOMAIN PROTEIN 1; OLIGODEOXYNUCLEOTIDE; PEPTIDOGLYCAN; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; POLYINOSINIC POLYCYTIDYLIC ACID; POLYPEPTIDE ANTIBIOTIC AGENT; PROBIOTIC AGENT; PROTEIN DERIVATIVE; T LYMPHOCYTE RECEPTOR; UNCLASSIFIED DRUG;

ANAPHYLACTIC SHOCK; B LYMPHOCYTE; BACTERIAL FLORA; CELL DAMAGE; CELL PROLIFERATION; CLEARANCE; COLITIS; CPG ISLAND; CROHN DISEASE; DNA POLYMORPHISM; ENTERITIS; ENTEROCOLITIS; GENE CONTROL; HEALTH; HEMOSTASIS; HUMAN; IDIOPATHIC DISEASE; INNATE IMMUNITY; INTESTINE EPITHELIUM CELL; INTESTINE FLORA; INTESTINE INFECTION; INTESTINE MUCOSA; MICROBIAL DIVERSITY; MOLECULAR EVOLUTION; MOLECULAR RECOGNITION; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; RADIATION INJURY; SALMONELLOSIS; SHORT SURVEY; SIGNAL TRANSDUCTION; SPECIES INVASION; T LYMPHOCYTE; WOUND HEALING;

EID: 17044385039     PISSN: 00221767     EISSN: None     Source Type: Journal    
DOI: 10.4049/jimmunol.174.8.4453     Document Type: Short Survey

References (104)

1. Rescigno, M., M. Urbano, B. Valzasina, M. Francolini, G. Rotta, R. Bonasio, F. Granucci, J. P. Kraehenbuhl, and P. Ricciardi-Castagnoli. 2001. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat. Immunol. 2:361.
2. Leveque, G., V. Forgetta, S. Morroll, A. L. Smith, N. Bumstead, P. Barrow, J. C. Loredo-Osti, K. Morgan, and D. Malo. 2003, Allelic variation in TLR4 is linked to susceptibility to Salmonella enterica serovar Typhimurium infection in chickens. Infect. Immun. 71:1116.
3. Hershberg, R. M. 2002. The epithelial cell cytoskeleton and intracellular trafficking: V. Polarized compartmentalization of antigen processing and Toll-like receptor signaling in intestinal epithelial cells. Am. J. Physiol. 283:G833.
4. Finegold, S. M., V. L. Sutter, P. T. Sugihara, H. A. Elder, S. M. Lehmann, and R. L. Phillips. 1977. Fecal microbial flora in Seventh Day Adventist populations and control subjects. Am. J. Clin. Nutr. 30:1781.
5. Abreu, M. T., P. Vora, E. Faure, L. S. Thomas, E. T. Arnold, and M. Arditi. 2001. Decreased expression of Toll-like receptor-4 and MD-2 correlates with intestinal epithelial cell protection against dysregulated proinflammatory gene expression in response to bacterial lipopolysaccharide. J. Immunol. 167:1609-
6. Naik, S., E. J. Kelly, L. Meijer, S. Pettersson, and I. R. Sanderson. 2001. Absence of Toll-like receptor 4. explains endotoxin hyporesponsiveness in human intestinal epithelium. J. Pediat. Gastroenterol. Nutr. 32:449.
7. Suzuki, M., T. Hisamatsu, and D. K. Podolsky. 2003. Gamma interferon augments the intracellular pathway for lipopolysaccharide (LPS) recognition in human intestinal epithelial cells through coordinated up-regulation of LPS uptake and expression of the intracellular Toll-like receptor 4-MD-2 complex. Infect. Immun. 71:3503.
8. Melmed, G., L. S. Thomas, N. Lee, S. Y. Tesfay, K. Lukasek, K. S. Michelsen, Y. Zhou, B. Hu, M. Arditi, and M. T. Abreu. 2003. Human intestinal epithelial cells are broadly unresponsive to Toll-like receptor 2-dependent bacterial ligands: implications for host-microbial interactions in the gut. J. Immunol. 170:1406.
9. Otte, J. M., E. Cario, and D. K. Podolsky. 2004. Mechanisms of cross hyporesponsiveness to Toll-like receptor bacterial ligands in intestinal epithelial cells. Gastroenterology 126:1054.
10. Gewirtz, A. T., T. A. Navas, S. Lyons, P. J. Godowski, and J. L Madara. 2001. Cutting edge: bacterial flagellin activates basolaterally expressed TLR5 to induce epithelial proinflammatory gene expression. J. Immunol. 167:1882.
11. Didierlaurent, A., J. C. Sirard, J. P. Kraehenbuhl, and M. R. Neutra. 2002. How the gut senses its content. Cell Microbiol. 4:61.
12. Reed, K. A., M. E. Hobert, C. E. Kolenda, K. A. Sands, M. Rathman, M. O'Connor, S. Lyons, A. T. Gewirtz, P. J. Sansonetti, and J. L. Madara. 2002. The Salmonella typhimurium flagellar basal body protein FIiE is required for flagellin production and to induce a proinflammatory response in epithelial cells. J. Biol. Chem. 277:13346.
13. Sierro, F., B. Dubois, A. Coste, D. Kaiserlian, J. P. Kraehenbuhl, and J. C. Sirard. 2001. Flagellin stimulation of intestinal epithelial cells triggers CCL20-mediated migration of dendritic cells. Proc. Natl. Acad. Sci. USA 98:13722.
14. Rhee, S. H., A. C. Keates, M. P. Mover, and C. Pothoulakis. 2004. MEK is a key modulator for TLR5-induced interleukin-8 and MIP3α gene expression in non-transformed human colonic epithelial cells. J. Biol. Chem. 279:25179.
15. Lodes, M. J., Y. Cong, C. O. Elson, R. Mohamath, C. J. Landers, S. R. Targan, M. Fort, and R. M. Hershberg. 2004. Bacterial flagellin is a dominant antigen in Crohn disease. J. Clin. Invest. 113:1296.
16. Hornef, M. W., B. H. Normark, A. Vandewalle, and S. Normark. 2003. Intracellular recognition of lipopolysaccharide by toll-like receptor 4 in intestinal epithelial cells. J. Exp. Med. 198:1225.
17. Hornef, M. W., T. Frisan, A. Vandewalle, S. Normark, and A. Richter-Dahlfors. 2002. Toll-like receptor 4 resides in the Golgi apparatus and colocalizes with internalized lipopolysaccharide in intestinal epithelial cells. J. Exp. Med. 195-559.
18. Hausmann, M., S. Kiessling, S. Mestermann, G. Webb, T. Spottl, T. Andus, J. Scholmerich, H. Herfarth, K. Ray, W. Falk, and G. Rogler. 2002. Toll-like receptors 2 and 4 are up-regulated during intestinal inflammation. Gastroenterology 122:1987.
19. Smith, P. D., L. E. Smythies, M. Mosteller-Barnum, D. A. Sibley, M. W. Russell, M. Merger, M. T. Sellers, J. M. Orenstein, T. Shimada, M. F. Graham, and H. Kubagawa. 2001. Intestinal macrophages lack CD14 and CD89 and consequently are down-regulated for LPS- and IgA-mediated activities. J. Immunol. 167:2651.
20. + regulatory T cells control T helper cell type 1 responses to foreign antigens induced by mature dendritic cells in vivo. J. Exp. Med. 198:259.
21. Burns, K., J. Clatworthy, L. Martin, F. Martinon, C. Plumpton, B. Maschera, A. Lewis, K. Ray, J. Tschopp, and F. Volpe. 2000. Tollip, a new component of the IL-IRI pathway, links IRAK to the IL-1 receptor. Nat. Cell Biol. 2:346.
22. Abreu, M. T., E. T. Arnold, L. S. Thomas, R. Gonsky, Y. Zhou, B. Hu, and M. Arditi. 2002, TLR4 and MD-2 expression is regulated by immune-mediated signals in human intestinal epithelial cells. J. Biol. Chem. 277:20431.
23. Wald, D., J. Qin, Z. Zhao, Y. Qian, M. Naramura, L. Tian, J. Towne, J. E. Sims, G. R. Stark, and X. Li. 2003. SIGIRR, a negative regulator of Toll-like receptor-interleukin 1 receptor signaling. Nat. Immunol. 4:920.
24. Garlanda, C., F. Riva, N. Polentarutti, C. Buracchi, M. Sitoni, M. De Bortoli, M. Muzio, R. Bergortini, E. Scanziani, A. Vecchi, et al. 2004. Intestinal inflammation in mice deficient in Tir8, an inhibitory member of the IL-1 receptor family. Proc. Natl. Acad. Sci. USA 101:3522.
25. Mantovani, A., M. Locati, N. Polentarutti, A. Vecchi, and C. Garlanda. 2004. Extracellular and intracellular decoys in the tuning of inflammatory cytokines and Toll-like receptors: the new entry TIR8/SIGIRR. J. Leukocyte Biol. 75:738.
26. Dubuquoy, L., E. A. Jansson, S. Deeb, S. Rakotobe, M. Karoui, J. F. Colombel, J. Auwerx, S. Pettersson, and P. Desreumaux. 2003. Impaired expression of peroxisome prolifetator-activated receptor γ in ulcerative colitis. Gastroenterology 124:1265.
27. Ganz, T. 2003. Defensins: antimicrobial peptides of innate immunity. Nat. Rev. Immunol. 3:710.
28. Yang, D., O. Chertov, S. N. Bykovskaia, Q. Chen, M. J. Buffo, J. Shogan, M. Anderson, J. M. Schroder, J. M. Wang, O. M. Howard, and J. J. Oppenheim. 1999. β-Defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science 286:525.
29. Porter, E. M., C. L. Bevins, D. Ghosh, and T. Ganz. 2002. The multifaceted Paneth cell. Cell. Mol. Life Sci. 59:156.
30. Ayabe, T., D. P. Satchell, C. L. Wilson, W. C. Parks, M. E. Selsted, and A. J. Ouellette. 2000. Secretion of microbicidal α-defensins by intestinal Paneth cells in response to bacteria. Nat. Immunol. 1:113.
31. Rumio, C., D. Besusso, M. Palazzo, S. Selleri, L. Sfondrini, F. Dubini, S. Menard, and A. Balsari. 2004. Degranulation of paneth cells via toll-like receptor 9. Am. J. Pathol. 165:373.
32. Hooper, L. V., T. S. Stappenbeck, C. V. Hong, and J. I. Gordon. 2003. Angiogenins: a new class of microbicidal proteins involved in innate immunity. Nat. Immunol. 4:269.
33. Fahlgren, A., S. Hammarstrom, A. Damelsson, and M. L. Hammarstrom. 2003. Increased expression of antimicrobial peptides and lysozyme in colonic epithelial cells of patients with ulcerative colitis. Clin. Exp. Immunol. 131:90.
34. Ogushi, K., A. Wada, T. Niidome, N. Mori, K. Oishi, T. Nagatake, A. Takahashi, H. Asakura, S. Makino, H. Hojo, et al. 2001. Salmonella, enteritidis FliC (flagella filament protein) induces human β-defensin-2 mRNA production by Caco-2 cells. J. Biol. Chem. 276:30521.
35. Ogushi, K., A. Wada, T. Niidome, T. Okuda, R. Llanes, M. Nakayama, Y. Nishi, H. Kurazono, K. D. Smith, A. Aderem, et al. 2004. Gangliosides act as co-receptors for Salmonella enteritidis FliC and promote FIiC induction of human β-defensin-2 expression in Caco-2 cells. J. Biol. Chem. 279:12213.
36. Vora, P., A. Youdim, L. S. Thomas, M. Fukata, S. Y. Tesfay, K. Lukasek, K. S. Michelsen, A. Wada, T. Hirayama, M. Arditi, and M. T. Abreu. 2004. β-Defensin-2 expression is regulated by TLR signaling in intestinal epithelial cells. J. Immunol. 173:5398.
37. Hooper, L. V., M. H. Wong, A. Thelin, L. Hansson, P. G. Falk, and J. I. Gordon. 2001. Molecular analysis of commensal host-microbial relationships in the intestine. Science 291:881.
38. Cario, E., G. Gerken, and D. K. Podolsky. 2004. Toll-like teceptor 2 enhances ZO-1-associated intestinal epithelial barrier integrity via protein kinase C. Gastroenterology 127:224.
39. Madsen, K., A. Cornish, P. Soper, C. McKaigney, H. Jijon, C. Yachimec, J. Doyle, L. Jewell, and C. De Simone. 2001. Probiotic bacteria enhance murine and human intestinal epithelial barrier function. Gastroenterology 121:580.
40. Resta-Lenert, S., and K. E. Barrett. 2003. Live probiotics protect intestinal epithelial cells from the effects of infection with enteroinvasive Escherichia coli (EIEC). Gut 52:988.
41. Madsen, K. L., J. S. Doyle, L. D. Jewell, M. M. Tavernini, and R. N. Fedorak. 1999. Lactobacillus species prevents colitis in interleukin 10 gene-deficient mice. Gastroenterology 116:1107.
42. Dieleman, L. A., M. S. Goerres, A. Arends, D. Sprengers, C. Torrice, F. Hoentjen, W. B. Grenther, and R. B. Sartor. 2003. Lactobacillus GG prevents recurrence of colitis in HLA-B27 transgenic rats after antibiotic treatment. Gut 52:370.
43. Schultz, M., C. Veltkamp, L. A. Dieleman, W. B. Grenther, P. B. Wyrick, S. L. Tonkonogy, and R. B. Sartor. 2002. Lactobacillus plantarum 299V in the treatment and prevention of spontaneous colitis in interleukin-10-deficient mice. Inflamm. Bowel Dis. 8:71.
44. Cetin, S., H. R. Ford, L. R. Sysko, C. Agarwal, J. Wang, M. D. Neal, C. Bary, G. Apodaca, and D. J. Hackam. 2004. Endotoxin inhibits intestinal epithelial restitution through activation of Rho-GTPase and increased focal adhesions. J. Biol. Chem. 279:24592.
45. Rakoff-Nahoum, S., J. Paglino, F. Eslami-Varzaneh, S. Edberg, and R. Medzhitov. 2004. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 118:229.
46. Abrams, G. D., H. Bauer, and H. Sprinz. 1903. Influence of the normal flora on mucosal morphology and cellular renewal in the ileum. A comparison of germ-free and conventional mice. Lab. Invest. 12:355.
47. Fukata, M., K. S. Michelsen, R. Eri, L. S. Thomas, B. Hu, K. Lukasek, C. C. Nast, J. Lechago, R. Xu, Y. Naiki, et al. 2005. Toll-like receptor-4 (TLR4) is required for the intestinal response to epithelial injury and limiting bacterial translocation in a murine model of acute colitis. Am. J. Physiol. Gastrointest. Liver Physiol. 288:G1055.
48. Kojima, K., M. W. Musch, M. J. Ropeleski, D. L. Boone, A. Ma, and E. B. Chang. 2004. Escherichia coli LPS induces heat shock protein 25 in intestinal epithelial cells through MAP ldnase activation. Am. J. Physiol. 286:G645.
49. Riehl, T., S. Cohn, T. Tessner, S. Schloemann, and W. F. Stenson. 2000. Lipopolysaccharide is radioprotective in the mouse intestine through a prostaglandin-mediated mechanism. Gastroenterology 118:1106.
50. McClelland, D. B. 1976. Peyer's-patch-associated synthesis of immunoglobulin in germ-free, specific-pathogen-free, and conventional mice. Scand. J. Immunol. 5:909.
51. + T cells. J. Immunol. 158:2099.
52. Papadakis, K. A., J. Prehn, S. T. Moreno, L. Cheng, E. A. Kouroumalis, R. Deem, T. Breaverman, P. D. Ponath, D. P. Andrew, P. H. Green, et al. 2001. CCR9-positive lymphocytes and thymus-expressed chemokine distinguish small bowel from colonic Crohn's disease. Gastroenterology 121:246.
53. Papadakis, K. A., C. Landers, J. Prehn, E. A. Kouroumalis, S. T. Moreno, J. C. Gutierrez-Ramos, M. R. Hodge, and S. R. Targan. 2003. CC chemokine receptor 9 expression defines a subset of peripheral blood lymphocytes with mucosal T cell phenotype and Th1 or T-regulatory 1 cytokine profile. J Immunol. 171:159.
54. Johansson-Lindbom, B., M. Svensson, M. A. Wurbel, B. Malissen, G. Marquez, and W. Agace. 2003. Selective generation of gut tropic T cells in gut-associated lymphoid tissue (GALT): requirement for GALT dendritic cells and adjuvant. J. Exp. Med. 198:963.
55. Stagg, A. J., M. A. Kamm, and S. C. Knight. 2002. Intestinal dendritic cells increase T cell expression of alpha4beta7 integrin. Eur. J. Immunol. 32:1445.
56. Jump, R. L., and A. D. Levine. 2004. Mechanisms of natural tolerance in the intestine: implications for inflammatory bowel disease. Inflamm. Bowel Dis. 10:462.
57. Duchmann, R., I. Kaiser, E. Hermann, W. Mayet, K. Ewe, and K. H. Meyer zum Buschenfelde. 1995. Tolerance exists towards resident intestinal flora but is broken in active inflammatory bowel disease (IBD). Clin. Exp. Immunol. 102:448.
58. Duchmann, R., M. F. Neurath, and K. H. Meyer zum Buschenfelde. 1997. Responses to self and non-self intestinal microflora in health and inflammatory bowel disease. Res. Immunol. 148:589.
59. Mow, W. S., E. A. Vasiliauskas, Y.-C. Lin, P. R. Fleshner, K. A. Papadakis, K. D. Taylor, C. J. Landers, M. T. Abreu, J. I. Rotter, H. Yang, and S. R. Targan. 2004. Association of antibody responses to microbial antigens and complications of small bowel Crohn's disease. Gastroenterology 126:414.
60. + T cell suppressor function. J. Immunol. 172:6519.
61. + regulatory T cells. J. Immunol. 170:3939.
62. Shirai, Y., M. Hashimoto, R. Kato, Y. I. Kawamura, T. Kirikae, H. Yano, J. Takashima, Y. Kirihara, Y. Saito, M. A. Fujino, and T. Dohi. 2004. Lipopolysaccharide induces CD25-positive, IL-10-producing lymphocytes without secretion of pro inflammatory cytokmes in the human colon: low MD-2 mRNA expression in colonic macrophages. J. Clin. Immunol. 24:42.
63. Uhlig, H. H., and F. Powrie. 2003. Dendriric cells and the intestinal bacterial flora: a role for localized mucosal immune responses. J. Clin. Invest. 112:648.
64. Stagg, A. J., A. L. Hart, S. C. Knight, and M. A. Kamm. 2003. The dendritic cell: its role in intestinal inflammation and relationship with gut bacteria. Gut 52:1522.
65. Macpherson, A. J., and T. Uhr. 2004. Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria. Science 303:1662.
66. Strober, W., I. J. Fuss, and R. S. Blumberg. 2002. The immunology of mucosal models of inflammation. Annual Review of Immunology 20:495.
67. Kobayashi, M., M. N. Kweon, H. Kuwata, R. D. Schreiber, H. Kiyono, K. Takeda, and S. Akira. 2003. Toll-like receptor-dependent production of IL-12p40 causes chronic enterocolitis in myeloid cell-specific Stat3-deficient mice. J. Clin. Invest. 111:1297.
68. Rachmilewitz, D., F. Karmeli, K. Takabayashi, T. Hayashi, L. Leider-Trejo, J. Lee, L. M. Leoni, and E. Raz. 2002. Immunostimulatory DNA ameliorates experimental and spontaneous mutine colitis. Gastroenterology 122:1428.
69. Rachmilewitz, D., K. Karakura, F. Karmeli, T. Hayashi, C. Reinus, B. Rudensky, S. Akira, K. Takeda, J. Lee, K. Takabayashi, and E. Raz. 2004. Toll-like receptor 9 signaling mediates the anti-inflammatory effects of probiotics in murine experimental coliris. Gastroenterology 126:520.
70. Torok, H. P., J. Glas, L. Tonenchi, G. Bruennler, M. Folwaczny, and C. Folwaczny. 2004. Crohn's disease is associated with a toll-like receptor-9 polymorphism. Gastroenterology 127:365.
71. Bashir, M. E., S. Louie, H. N. Shi, and C. Nagler-Anderson. 2004. Toll-like receptor 4 signaling by intestinal microbes influences susceptibility to food allergy. J. Immunol. 172:6978.
72. Athman, R., and D. Philpott. 2004. Innate immunity via Toll-like receptors and Nod proteins. Curr. Opin. Microbiol. 7:25.
73. Chamaillard, M., S. E. Girardin, J. Viala, and D. J. Philpott. 2003. Nods, Nalps and Naip: intracellular regulators of bacterial-induced inflammation. Cell. Microbiol. 5:581.
74. Inohara, N., Y. Ogura, F. F. Chen, A. Muto, and G. Nunez. 2001, Human Nod1 confers responsiveness to bacterial lipopolysaccharides. J. Biol. Chem. 276:2551.
75. Ogura, Y., N. Inohara, A. Benito, F. F. Chen, S. Yamaoka, and G. Nunez. 2001. Nod2, a Nod1/Apaf-1 family member that is restricted to monocytes and activates NF-κB. J. Biol. Chem. 276:4812.
76. Kobayashi, K., N. Inohara, L. D. Hernandez, J. E. Galan, G. Nunez, C. A. Janeway, R. Medzhitov, and R. A. Flavell, 2002. RICK/Rip2/CARDIAK mediates signalling for receptors of the innate and adaptive immune systems. Nature 416:194.
77. Girardin, S. E., I. G. Boneca, L. A. Carneiro, A. Antignac, M. Jehanno, J. Viala, K. Tedin, M. K. Taha, A. Labigne, U. Zathringer, et al. 2003. Nod1 detects a unique muropeptide from gram-negative bacterial peptidoglyean. Science 300:1584.
78. Kim, J. G., S. J. Lee, and M. F. Kagnoff. 2004. Nod1 is an essential signal transducer in intestinal epithelial cells infected with bacteria chat avoid recognition by toll-like receptors. Infect. Immun. 72:1487.
79. Girardin, S. E., I. G. Boneca, J. Viala, M. Chamaillard, A. Labigne, G. Thomas, D. J. Philpotr, and P. J. Sansonetti. 2003. Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection. J. Biol. Chem. 278:8869.
80. Lala, S., Y. Ogura, C. Osborne, S. Y. Hor, A. Bromfield, S. Davies, O. Ogunbiyi, G. Nunez, and S. Keshav. 2003. Crohn's disease and the NOD2 gene: a role for paneth cells. Gastroenterology 125:47.
81. Gutierrez, O., C. Pipaon, N. Inohara, A. Fontalba, Y. Ogura, F. Prosper, G. Nunez, and J. L. Fernandez-Luna. 2002. Induction of Nod2 in myelomonocytic and intestinal epithelial cells via nuclear factor-κ B activation. J. Biol. Chem. 277:41701.
82. Rosenstiel, P., M. Fantini, K. Brautigam, T. Kuhbacker, G. H. Waetzig, D. Seegert, and S. Schreiber. 2003. TNF-α and IFN-γ regulate the expression of the NOD2 (CARD15) gene in human intestinal epithelial cells. Gastroenterology 124:1001.
83. Berrebi, D., R. Maudinas, J. P. Hugot, M. Chamaillard, F. Chareyre, P. De Lagausie, C. Yang, P. Desreumaux, M. Giovannini, J. P. Cezard, et al. 2003. Card15 gene overexpression in mononuclear and epithelial cells of the inflamed Crohn's disease colon. Gut 52:840.
84. Ogura, Y., D. K. Bonen, N. Inohara, D. L. Nicolae, F. F. Chen, R. Ramos, H. Britton, T. Moran, R. Karaliuskas, R. H. Duerr, et al. 2001. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature 411:603.
85. Hugoc, J. P., M. Chamaillard, H. Zouali, S. Lesage, J. P. Cezard, J. Belaiche, S. Almer, C. Tysk, C. A. O'Morain, M. Gassull, et al. 2001. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 411:599.
86. Maeda, S., L. C. Hsu, H. Liu, L. A. Bankston, M. Iimura, M. F. Kagnoff, L. Eckmann, and M. Karin. 2005. Nod2 mutation in Crohn's disease potentiates NF-κB activity and IL-1β processing. Science 307:734.
87. Netea, M. G., B. J. Kullberg, D. J. De Jong, B. Franke, T. Sprong, T. H. Naber, J. P. Drenth, and J. W. Van Der Meer. 2004. NOD2 mediates anti-inflammatory signals induced by TLR2 ligands: implications for Crohn's disease. Eur. J. Immunol. 34:2052.
88. Rock, F. L., G. Hardiman, J. C. Timans, R. A. Kastelein, and J. F. Bazan. 1998. A family of human receptors structurally related to Drosophila Toll. Proc. Natl. Acad. Sci. USA 95:588.
89. Catio, E., and D. K. Podolsky. 2000. Differential alteration in intestinal epithelial cell expression of toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease. Infect. Immun. 68:7010.
90. Du, X., A. Poltotak, Y. Wei, and B. Beutler. 2000. Three novel mammalian toll-like receptors: gene structure, expression, and evolution. Eur. Cytokine Network 11:362.
91. Chuang, T., and R. J. Ulevitch. 2001. Identification of hTLR10: a novel human Toll-like receptor preferentially expressed in immune cells. Biochim. Biophys. Acta. 1518: 157.
92. Cario, E., I. M. Rosenberg, S. L. Brandwein, P. L. Beck, H. C. Reinecker, and D. K. Podolsky. 2000. Lipopolysaccharide activates distinct signaling pathways in intestinal epithelial cell lines expressing Toll-like receptors. J. Immunol. 164:966.
93. Bambou, J. C., A. Giraud, S. Menard, B. Begue, S. Rakotobe, M. Heyman, F. Taddei, N. Cerf-Bensussan, and V. Gaboriau-Routhiau. 2004. In vitro and ex vivo activation of the TLR5 signaling pathway in intestinal epithelial cells by a commensal Escherichia coli strain. J. Biol. Chem. 279:42984.
94. Akhtar, M., J. L. Watson, A. Nazli, and D. M. McKay. 2003. Bacterial DNA evokes epithelial IL-8 production by a MAPK-dependent, NF-κB-independent pathway. FASEB J. 17:1319.
95. Otte, J. M., I. M. Rosenberg, and D. K. Podolsky. 2003. Intestinal myofibroblasts in innate immune responses of the intestine. Gastroenterology 124:1866.
96. Muzio, M., D. Bosisio, N. Polentarutti, G. D'Amico, A. Stoppacciaro, R. Mancinelli, C. van't Veer, G. Penton-Rol, L. P. Ruco, P. Allavena, and A. Mantovani. 2000. Differential expression and regulation of toll-like receprors (TLR) in human leukocytes: selective expression of TLR3 in dendriric cells. J. Immunol. 164:5998.
97. Marsik, C., F. Mayr, F. Cardona, U. Derhaschnig, O. F. Wagner, and B. Jilma. 2003. Endotoxaemia modulates Toll-like receptors on leucocytes in humans. Br. J. Haematol. 121:653.
98. Hornung, V., S. Rothenfusser, S. Britsch, A. Krug, B. Jahrsdorfer, T. Giese, S. Endres, and G. Hartmann. 2002. Quantitative expression of toll-like receptor 1-10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides. J. Immunol. 168:4531.
99. Beliocchio, S., S. Moretti, K. Perruccio, F. Fallarino, S. Bozza, C. Montagnoli, P. Mosci, G. B. Lipford, L. Pitzurra, and L. Romani. 2004. TLRs govern neutrophil activity in aspergillosis. J. Immunol. 173:7406.
100. Ortega-Cava, C. F., S. Ishihara, M. A. Rumi, K. Kawashima, N. Ishimura, H. Kazumori, J. Udagawa, Y. Kadowaki, and Y. Kinoshita. 2003. Strategic compartmentalization of toll-like receptor 4 in the mouse gut. J. Immunol. 170:3977.
101. Ogawa, H., P. Rafiee, J. Heidemann, P. J. Fisher, N. A. Johnson, M. F. Otterson, B. Kalyanaraman, K. A. Pritchard, Jr., and D. G. Binion. 2003. Mechanisms of endotoxin tolerance in human intestinal microvascular endothelial cells. J. Immunol. 170:5956.
102. Maaser, C., J. Heidemann, C. von Eiff, A. Lugering, T. W. Spahn, D. G. Binion, W. Domichke, N. Lugering, and T. Kuckarzik. 2004. Human intestinal microvascular endothelial cells express Toll-like receptor 5: a binding partner for bacterial flagellin. J. Immunol. 172:5056.
103. Re, F., and J. L. Strominger. 2004. IL-10 released by concomitant TLR2 stimulation blocks the induction of a subset of Th1 cytokines that are specifically induced by TLR4 or TLR3 in human dendritic cells. J. Immunol. 173:7548.
104. Singh, J. C., S. M. Cruickshank, D. J. Newton, L. Wakenshaw, A. Graham, J. Lan, J. P. Lodge, P. J. Felsburg, and S. R. Carding. 2005. Toll-like receptor-mediated responses of primary intestinal epithelial cells during the development of colitis. Am J. Physiol. 288:G514.