Innate Immunity

Physiology of the Gastrointestinal Tract

Volumn 2, Issue , 2006, Pages 1033-1066

  Eckmann, Lars ^a  

^a UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84883909916     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1016/B978-012088394-3/50045-3     Document Type: Chapter

References (364)

1. Kimbrell DA, Beutler B The evolution and genetics of innate immunity. Nat Rev Genet 2001, 2:256-267.
2. Kasahara M, Suzuki T, Pasquier LD On the origins of the adaptive immune system: novel insights from invertebrates and cold-blooded vertebrates. Trends Immunol 2004, 25:105-111.
3. Cannon JP, Haire RN, Rast JP, Litman GW The phylogenetic origins of the antigen-binding receptors and somatic diversification mechanisms. Immunol Rev 2004, 200:12-22.
4. Anderson KV, Bokla L, Nusslein-Volhard C Establishment of dorsal-ventral polarity in the Drosophila embryo: the induction of polarity by the Toll gene product. Cell 1985, 42:791-798.
5. Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 1996, 86:973-983.
6. Medzhitov R, Preston-Hurlburt P, Janeway CA A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 1997, 388:394-397.
7. Takeda K, Kaisho T, Akira S Toll-like receptors. Annu Rev Immunol 2003, 21:335-376.
8. Beutler B, Hoebe K, Georgel P, Tabeta K, Du X Genetic analysis of innate immunity: TIR adapter proteins in innate and adaptive immune responses. Microbes Infect 2004, 6:1374-1381.
9. Zarember KA, Godowski PJ Tissue expression of human Toll-like receptors and differential regulation of Toll-like receptor mRNAs in leukocytes in response to microbes, their products,. J Immunol 2002, 168:554-561.
10. Beutler B, Rietschel ET Innate immune sensing and its roots: the story of endotoxin. Nat Rev Immunol 2003, 3:169-176.
11. Hausmann M, Kiessling S, Mestermann S, Webb G, Spottl T, Andus T, Scholmerich J, Herfarth H, Ray K, Falk W, Rogler G Toll-like recep-tors 2 and 4 are up-regulated during intestinal inflammation. Gastroenterology 2002, 122:1987-2000.
12. Cario E, Podolsky DK Differential alteration in intestinal epithelial cell expression of toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease. Infect Immun 2000, 68:7010-7017.
13. Ogawa H, Rafiee P, Heidemann J, Fisher PJ, Johnson NA, Otterson MF, Kalyanaraman B, Pritchard KA, Binion DG Mechanisms of endotoxin tolerance in human intestinal microvascular endothelial cells. J Immunol 2003, 170:5956-5964.
14. Uhrig A, Banafsche R, Kremer M, Hegenbarth S, Hamann A, Neurath M, Gerken G, Limmer A, Knolle PA Development and functional conse-quences of LPS tolerance in sinusoidal endothelial cells of the liver. J Leukoc Biol 2005, 77:626-633.
15. Otte JM, Rosenberg IM, Podolsky DK Intestinal myofibroblasts in innate immune responses of the intestine. Gastroenterology 2003, 124:1866-1878.
16. Suzuki M, Hisamatsu T, Podolsky DK Gamma interferon augments the intracellular pathway for lipopolysaccharide (LPS) recognition in human intestinal epithelial cells through coordinated up-regul uptake and expression of the intracellular Toll-like receptor 4-MD-2 complex. Infect Immun 2003, 71:3503-3511.
17. Abreu MT, Vora P, Faure E, Thomas LS, Arnold ET, Arditi M Decreased expression of Toll-like receptor-4 and MD-2 correlates with intestinal epithelial cell protection against dysregulated proinflamma-tory gene express to bacterial lipopolysaccharide. J Immunol 2001, 167:1609-1616.
18. Abreu MT, Arnold ET, Thomas LS, Gonsky R, Zhou Y, Hu B, Arditi M TLR4 and MD-2 expression is regulated by immune-mediated signals in human intestinal epithelial cells. J Biol Chem 2002, 277:20431-20437.
19. Schmausser B, Andrulis M, Endrich S, Lee SK, Josenhans C, Muller-Hermelink HK, Eck M Expression subcellular distribution of toll-like receptors TLR4. Clin Exp Immunol 2004, 136:521-526.
20. Shimazu R, Akashi S, Ogata H, Nagai Y, Fukudome K, Miyake K, Kimoto M MD-2 a molecule that confers lipopolysaccharide respon-siveness on Toll-like receptor 4. J Exp Med 1999, 189:1777-1782.
21. Viriyakosol S, Tobias PS, Kitchens RL, Kirkland TN MD-2 binds to bacterial lipopolysaccharide. J Biol Chem 2001, 276:38044-38051.
22. Poltorak A, Ricciardi-Castagnoli P, Citterio S, Beutler B Physical contact between lipopolysaccharide and toll-like receptor 4 revealed by genetic complementation. Proc Natl Acad Sci USA 2000, 97:2163-2167.
23. Fitzgerald KA, Rowe DC, Golenbock DT Endotoxin recognition and signal transduction by the TLR4/MD2-complex. Microbes Infect 2004, 6:1361-1367.
24. Park JM, Ng VH, Maeda S, Rest RF, Karin M Anthrolysin O and other gram-positive cytolysins are toll-like receptor 4 agonists. J Exp Med 2004, 200:1647-1655.
25. Tsan MF, Gao B Endogenous ligands of Toll-like receptors. J Leukoc Biol 2004, 76:514-519.
26. Smythies LE, Sellers M, Clements RH, Mosteller-Barnum M, Meng G, Benjamin WH, Orenstein JM, Smith PD Human intestinal macrophages display profound inflammatory anergy despite avid phagocytic and bacteriocidal activity. J Clin Invest 2005, 115:66-75.
27. Grimm MC, Pavli P, Van de Pol E Doe WE Evidence for a CD14+ population of monocytes in inflammatory bowel disease mucosa-implications for pathogenesis. Clin Exp Immunol 1995, 100:291-297.
28. Rogler G, Andus T, Aschenbrenner E, Vogl D, Falk W, Scholmerich J Gross V Alterations of the phenotype of colonic macrophages in inflammatory bowel disease. Eur J Gastroenterol Hepatol 1997, 9:893-899.
29. Grimm MC, Pullman WE, Bennett GM, Sullivan PJ, Pavli P Doe WE Direct evidence of monocyte recruitment to inflammatory bowel disease mucosa. J Gastroenterol Hepatol 1995, 10:387-395.
30. Rugtveit J, Nilsen EM, Bakka A, Carlsen H, Brandtzaeg P, Scott H Cytokine profiles differ in newly recruited and resident subsets of mucosal macrophages from inflammatory bowel disease. Gastroenterology 1997, 112:1493-1505.
31. Hornef MW, Frisan T, Vandewalle A, Normark S, Richter-Dahlfors A Toll-like receptor 4 resides in the Golgi apparatus and colocalizes with internalized lipopolysaccharide in intestinal epithelial cells. J Exp Med 2002, 195:559-570.
32. Hornef MW, Normark BH, Vandewalle A, Normark S Intracellular recognition of lipopolysaccharide by toll-like receptor 4 in intestinal epithelial cells. J Exp Med 2003, 198:1225-1235.
33. Hoebe K, Du X, Georgel P, Janssen E, Tabeta K, Kim SO, Goode J, Lin P, Mann N, Mudd S, Crozat K, Sorath S, Han J, Beutler B Identification of Lps2 as a key transducer of MyD88-independent TIR signalling. Nature 2003, 424:743-748.
34. Jiang Z, Georgel P, Du X, Shamel L, Sovath S, Mudd S, Huber M, Kalis C, Keck S, Galanos C, Freudenberg M, Beutler B CD 14 is required for MyD88-independent LPS signaling. Nat Immunol 2005, 6:565-570.
35. Hoshino K, Takeuchi O, Kawai T, Sanjo H, Ogawa T, Takeda Y, Takeda K, Akira S Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the LPS gene product. J Immunol 1999, 162:3749-3752.
36. Nagai Y, Akashi S, Nagafuku M, Ogata M, Iwakura Y, Akira S, Kitamura T, Kosugi A, Kimoto M, Miyake K Essential role of MD-2 in LPS responsiveness and TLR4 distribution. Nat Immunol 2002, 3:667-672.
37. Jack RS, Fan X, Bernheiden M, Rune G, Ehlers M, Weber A, Kirsch G, Mentel R, Furll B, Freudenberg M, Schmitz G, Stelter F, Schutt C Lipopolysaccharide-binding protein is required to combat a murine gram-negative bacterial infection. Nature 1997, 389:742-745.
38. Haziot A, Ferrero E, Kontgen F, Hijiya N, Yamamoto S, Silver J, Stewart CL, Goyert SM Resistance to endotoxin shock and reduced dissemination of gram-negative bacteria in CD14-deficient mice. Immunity 1996, 4:407-414.
39. Arbour NC, Lorenz E, Schutte BC, Zabner J, Kline JN, Jones M, Frees K, Watt JL, Schwartz DA TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat Genet 2000, 25:187-191.
40. Fierer J, Swancutt MA, Heumann D, Golenbock D The role of lipopolysaccharide binding protein in resistance to Salmonella infec-tions in mice. J Immunol 2002, 168:6396-6403.
41. Knapp S, de Vos AF, Florquin S, Golenbock DT, van der Poll T Lipopolysaccharide binding protein is an essential component of the innate immune response to Escherichia coli peritonitis in mice. Infect Immun 2003, 71:6747-6753.
42. Weiss DS, Raupach B, Takeda K, Akira S, Zychlinsky A Toll-like receptors are temporally involved in host defense. J Immunol 2004, 172:4463-4469.
43. Vazquez-Torres A, Vallance BA, Bergman MA, Finlay BB, Cookson BT, Jones-Carson J, Fang FC Toll-like receptor 4 dependence of innate and adaptive immunity to Salmonella: importance of the Kupffer cell network. J Immunol 2004, 172:6202-6208.
44. Le Roy D, Di Padova F, Adachi Y, Glauser MP, Calandra T, Heumann D Critical role of lipopolysaccharide-binding protein and CD 14 in immune responses against gram-negative bacteria. J Immunol 2001, 167:2759-2765.
45. Bihl F, Salez L, Beaubier M, Torres D, Lariviere L, Laroche L, Benedetto A, Martel D, Lapointe JM, Ryffel B, Malo D Overexpression of Toll-like receptor 4 amplifies the host response to lipopolysaccharide and provides a survival advantage in transgenic mice. J Immunol 2003, 170:6141-6150.
46. Kiechl S, Lorenz E, Reindl M, Wiedermann CJ, Oberhollenzer F, Bonora E, Willeit J, Schwartz DA Toll-like receptor 4 polymorphisms and atherogenesis. N Engl J Med 2002, 347:185-192.
47. Lorenz E, Mira JP, Frees KL, Schwartz DA Relevance of mutations in the TLR4 receptor in patients with gram-negative septic shock. Arch Intern Med 2002, 162:1028-1032.
48. Kursar M, Mittrucker HW, Koch M, Kohler A, Herma M, Kaufmann SH Protective T cell response against intracellular pathogens in the absence of Toll-like receptor signaling via myeloid differentiation factor 88. Int Immunol 2004, 16:415-421.
49. Branger J, Florquin S, Knapp S, Leemans JC, Pater JM, Speelman P, Golenbock DT, van der Poll T LPS-binding protein-deficient mice have an impaired defense against Gram-negative but not Gram-positive pneumonia. Int Immunol 2004, 16:1605-1611.
50. Helmby H, Grencis RK Essential role for TLR4 and MyD88 in the development of chronic intestinal nematode infection. Eur J Immunol 2003, 33:2974-2979.
51. Bashir ME, Louie S, Shi HN, Nagler-Anderson C Toll-like receptor 4 signaling by intestinal microbes influences susceptibility to food allergy. J Immunol 2004, 172:6978-6987.
52. Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, Edberg S, Medzhitov R Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 2004, 118:229-241.
53. Fukata M, Michelsen KS, Eri R, Thomas LS, Hu B, Lukasek K, Nast CC, Lechago J, Xu R, Naiki Y, Soliman A, Arditi M, Abreu MT Toll-like receptor-4 is required for intestinal response to epithelial injury and limiting bacterial translocation in a murine model of acute colitis. Am J Physiol Gastrointest Liver Physiol 2005, 288:G1055-G1065.
54. Fort MM, Mozaffarian A, Stover AG, Correia JDAS, Johnson DA, Crane RT, Ulevitch RJ, Persing DH, Bielefeldt-Ohmann H, Probst P, Jeffery E, Fling SP, Hershberg RM A synthetic TLR4 antagonist has anti-inflammatory effects in two murine models of inflammatory bowel disease. J Immunol 2005, 174:6416-6423.
55. Rachmilewitz D, Katakura K, Karmeli F, Hayashi T, Reinus C, Rudensky B, Akira S, Takeda K, Lee J, Takabayashi K, Raz E Toll-like receptor 9 signaling mediates the anti-inflammatory effects of probiotics in murine experimental colitis. Gastroenterology 2004, 126:520-528.
56. Stevceva L, Pavli P, Buffinton G, Wozniak A, Doe WF Dextran sodium sulphate-induced colitis activity varies with mouse strain but develops in lipopolysaccharide-unresponsive mice. J Gastroenterol Hepatol 1999, 14:54-60.
57. Lange S, Delbro DS, Jennische E, Mattsby-Baltzer I The role of the Lps gene in experimental ulcerative colitis in mice. Apmis 1996, 104:823-833.
58. Kobayashi M, Kweon MN, Kuwata H, Schreiber RD, Kiyono H, Takeda K, Akira S Toll-like receptor-dependent production of IL-12p40 causes chronic enterocolitis in myeloid cell-specific Stat3-deficient mice. J Clin Invest 2003, 111:1297-1308.
59. Isaacs KL, Sartor RB Treatment of inflammatory bowel disease with antibiotics. Gastroenterol Clin North Am 2004, 33:335-345.
60. Franchimont D, Vermeire S, El Housni H, Pierik M, Van Steen K, Gustot T, Quertinmont E, Abramowicz M, Van Gossum A, Deviere J, Rutgeerts P Deficient host-bacteria interactions in inflammatory bowel disease? The toll-like receptor (TLR) -4 Asp299gly polymorphism is associated with Crohn's disease colitis. Gut 2004, 53:987-992.
61. Brand S, Staudinger T, Schnitzler F, Pfennig S, Hofbauer K, Dambacher J, Seiderer J, Tillack C, Konrad A, Crispin A, Goke B, Lohse P, Ochsenkuhn T The role of Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms and CARD15/NOD2 mutations in the suscep-tibility and phenotype of Crohn's disease. Inflamm Bowel Dis 2005, 11:645-652.
62. Rath HC, Herfarth HH, Ikeda JS, Grenther WB, Hamm TE, Balish E, Taurog JD, Hammer RE, Wilson KH, Sartor RB Normal luminal bacteria, especially Bacteroides species, mediate chronic colitis, gastritis, and arthritis in HLA-B27/human beta2 microglobulin transgenic rat. J Clin Invest 1996, 98:945-953.
63. Hornung V, Rothenfusser S, Britsch S, Krug A, Jahrsdorfer B, Giese T, Endres S, Hartmann G Quantitative expression of toll-like receptor 1-10 mRNA in cellular subsets of human peripheral blood mononuclear Innate Immunity/1059 cells and sensitivity oligodeoxynucleotides. J Immunol 2002, 168:4531-4537.
64. Nakao Y, Funami K, Kikkawa S, Taniguchi M, Nishiguchi M, Fukumori Y, Seya T, Matsumoto M Surface-expressed TLR6 participates in the recognition of diacylated lipopeptide and peptidoglycan in human cells. J Immunol 2005, 174:1566-1573.
65. Hart AL, Al-Hassi HO, Rigby RJ, Bell SJ, Emmanuel AV, Knight SC, Kamm MA, Stagg AJ Characteristics of intestinal dendritic cells in inflammatory bowel diseases. Gastroenterology 2005, 129:50-65.
66. Komai-Koma M, Jones L, Ogg GS, Xu D, Liew FY TLR2 is expressed on activated T cells as a costimulatory receptor. Proc Natl Acad Sci USA 2004, 101:3029-3034.
67. Melmed G, Thomas LS, Lee N, Tesfay SY, Lukasek K, Michelsen KS, Zhou Y, Hu B, Arditi M, Abreu MT Human intestinal epithelial cells are broadly unresponsive to Toll-like receptor 2-dependent bacterial ligands: implications for host-microbial interactions i. J Immunol 2003, 170:1406-1415.
68. Vora P, Youdim A, Thomas LS, Fukata M, Tesfay SY, Lukasek K, Michelsen KS, Wada A, Hirayama T, Arditi M, Abreu MT Beta-defensin-2 expression is regulated by TLR signaling in intestinal epithelial cells. J Immunol 2004, 173:5398-5405.
69. Cario E, Gerken G, Podolsky DK Toll-like receptor 2 enhances ZO-1-associated intestinal epithelial barrier integrity via protein kinase C. Gastroenterology 2004, 127:224-238.
70. Dziarski R, Gupta D Staphylococcus aureus peptidoglycan is a toll-like receptor 2 activator: a reevaluation. Infect Immun 2005, 73:5212-5216.
71. Schwandner R, Dziarski R, Wesche H, Rothe M, Kirschning CJ Peptidoglycan-and lipoteichoic acid-induced cell activation is mediated by toll-like receptor 2. J Biol Chem 1999, 274:17406-17409.
72. Means TK, Wang S, Lien E, Yoshimura A, Golenbock DT Fenton MX Human toll-like receptors mediate cellular activation by Mycobacterium tuberculosis. J Immunol 1999, 163:3920-3927.
73. Underhill DM, Ozinsky A, Hajjar AM, Stevens A, Wilson CB, Bassetti M, Aderem A The Toll-like receptor 2 is recruited to macrophage phago-somes and discriminates between pathogens. Nature 1999, 401:811-815.
74. Vasselon T, Derniers PA, Charron D, Haziot A TLR2 recognizes a bacterial lipopeptide through direct binding. J Immunol 2004, 173:7401-7405.
75. Manukyan M, Triantafilou K, Triantafilou M, Mackie A, Nilsen N, Espevik T, Wiesmuller KH, Ulmer AJ, Heine H Binding of lipopeptide to CD14 induces physical proximity of CD14. Eur J Immunol 2005, 35:911-921.
76. Ozinsky A, Underhill DM, Fontenot JD, Hajjar AM, Smith KD, Wilson CB, Schroeder L, Aderem A The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll-like receptors. Proc Natl Acad Sci USA 2000, 97:13766-13771.
77. Takeuchi O, Kawai T, Muhlradt PF, Morr M, Radolf JD, Zychlinsky A, Takeda K, Akira S Discrimination of bacterial lipoproteins by Toll-like receptor 6. Int Immunol 2001, 13:933-940.
78. Takeuchi O, Sato S, Horiuchi T, Hoshino K, Takeda K, Dong Z, Modlin RL, Akira S Cutting edge: role of Toll-like receptor 1 in medi-ating immune response to microbial lipoproteins. J Immunol 2002, 169:10-14.
79. Yamamoto M, Sato S, Hemmi H, Sanjo H, Uematsu S, Kaisho T, Hoshino K, Takeuchi O, Kobayashi M, Fujita T, Takeda K, Akira S Essential role for TIRAP in activation of the signalling cascade shared by TLR2 and TLR4. Nature 2002, 420:324-329.
80. Horng T, Barton GM, Flavell RA, Medzhitov R The adaptor molecule TIRAP provides signalling specificity for Toll-like receptors. Nature 2002, 420:329-333.
81. Aliprantis AO, Yang RB, Weiss DS, Godowski P, Zychlinsky A The apoptotic signaling pathway activated by Toll-like receptor-2. EMBO J 2000, 19:3325-3336.
82. Toshchakov V, Jones BW, Perera PY, Thomas K, Cody MJ, Zhang S, Williams BR, Major J, Hamilton TA, Fenton MJ, Vogel SN Mediates IFN-beta-induced STATlalphafoeta-dependent gene expression in macrophages. Nat Immunol 2002, 3:392-398. TLR4 but not TLR2.
83. Torres D, Barrier M, Bihl F, Quesniaux VJ, Maillet I, Akira S, Ryffel B, Erard F Toll-like receptor 2 is required for optimal control of Listeria monocytogenes infection. Infect Immun 2004, 72:2131-2139.
84. Edelson BT, Unanue ER MyD88-dependent but Toll-like receptor 2-independent innate immunity to Listeria: no role for either in macrophage listericidal activity. J Immunol 2002, 169:3869-3875.
85. Echchannaoui H, Frei K, Schnell C, Leib SL, Zimmerli W, Landmann R Toll-like receptor 2-deficient mice are highly susceptible to Streptococcus pneumoniae meningitis because of reduced bacterial clearing and enhanced inflammat. J Infect Dis 2002, 186:798-806.
86. Georgel P, Crozat K, Lauth X, Makrantonaki E, Seitmann H, Sovath S, Hoebe K, Du X, Rutschmann S, Jiang Z, Bigby T, Nizet V, Zouboulis CC, Beutler B A toll-like receptor 2-responsive lipid effector pathway protects mammals against skin infections with gram-positive bacteria. Infect Immun 2005, 73:4512-4521.
87. Biondo C, Midiri A, Messina L, Tomasello F, GarufiG, Catania MR, Bombaci M, Beninati C, Teti G, Mancuso G MyD88 and TLR2, but not TLR4, are required for host defense against Cryptococcus neoformans. Eur J Immunol 2005, 35:870-878.
88. Levitz SM Interactions of Toll-like receptors with fungi. Microbes Infect 2004, 6:1351-1355.
89. Netea MG, Sutmuller R, Hermann C, Van der Graaf CA, Van der Meer JW, van Krieken JH, Härtung T, Adema G, Kullberg BJ Toll-like receptor 2 suppresses immunity against Candida albicans through induction of IL-10 and regulatory T cells. J Immunol 2004, 172:3712-3718.
90. Kim SC, Tonkonogy SL, Albright CA, Tsang J, Balish EJ, Braun J, Huycke MM, Sartor RB Variable phenotypes of enterocolitis in inter-leukin 10-deficient mice monoassociated with two different commen-sal bacteria. Gastroenterology 2005, 128:891-906.
91. Redecke V, Hacker H, Datta SK, Fermin A, Pitha PM, Broide DH, Raz E Cutting edge: activation of Toll-like receptor 2 induces a Th2 immune response and promotes experimental asthma. J Immunol 2004, 172:2739-2743.
92. Strober W, Fuss IJ, Blumberg RS The immunology of mucosal models of inflammation. Annu Rev Immunol 2002, 20:495-549.
93. Wagner H The immunobiology of the TLR9 subfamily. Trends Immunol 2004, 25:381-386.
94. Rumio C, Besusso D, Palazzo M, Selleri S, Sfondrini L, Dubini F, Menard S, Balsari A Degranulation of paneth cells via toll-like receptor 9. Am J Pathol 2004, 165:373-381.
95. Shimosato T, Tohno M, Kitazawa H, Katoh S, Watanabe K, Kawai Y, Aso H, Yamaguchi T, Saito T Toll-like receptor 9 is expressed on folli-cle-associated epithelia containing M cells in swine Peyer's patches. Immunol Lett 2005, 98:83-89.
96. Saikh KU, Kissner TL, Sultana A, Ruthel G, Ulrich RG Human monocytes infected with Yersinia pestis express cell surface TLR9 and differentiate into dendritic cells. J Immunol 2004, 173:7426-7434.
97. Pedersen G, Andresen L, Matthiessen MW, Rask-Madsen J, Brynskov J Expression of Toll-like receptor 9 and response to bacterial CpG oligodeoxynucleotides in human intestinal epithelium. Clin Exp Immunol 2005, 141:298-306.
98. Totemeyer S, Kaiser P, Maskell DJ, Bryant CE Sublethal infection of C57BL/6 mice with Salmonella enterica Serovar Typhimurium leads to an increase in levels of Toll-like receptor 1 (TLR1), TLR2, and TLR9 as a decrease in levels of TLR6 mRNA in infected organs. Infect Immun 2005, 73:1873-1878.
99. Hemmi H, Takeuchi O, Kawai T, Kaisho T, Sato S, Sanjo H, Matsumoto M, Hoshino K, Wagner H, Takeda K, Akira S A Toll-like receptor recognizes bacterial DNA. Nature 2000, 408:740-745.
100. Stacey KJ, Young GR, Clark F, Sester DP, Roberts TL, Naik S, Sweet MJ, Hume DA The molecular basis for the lack of immunostimulatory activity of vertebrate DNA. J Immunol 2003, 170:3614-3620.
101. Hacker H, Mischak H, Miethke T, Liptay S, Schmid R, Sparwasser T, Heeg K, Lipford GB, Wagner H CpG-DNA-specific activation of antigen-presenting cells requires stress kinase activity and is preceded by non-specific endocytosis and endosomal maturation. EMBO J 1998, 17:6230-6240.
102. Burge C, Campbell AM, Karlin S Over-and under-representation of short oligonucleotides in DNA sequences. Proc Natl Acad Sci USA 1992, 89:1358-1362.
103. Takeshita F, Leifer CA, Gursel I, Ishii KJ, Takeshita S, Gursel M, Klinman DM Cutting edge: role of Toll-like receptor 9 in CpG DNA-induced activation of human cells. J Immunol 2001, 167:3555-3558.
104. Feinberg AP, Cui H, Ohlsson R DNA methylation and genomic imprinting: insights from cancer into epigenetic mechanisms. Semin Cancer Biol 2002, 12:389-398.
105. Caiafa P, Zampieri M DNA methylation and chromatin structure: the puzzling CpG islands. J Cell Biochem 2005, 94:257-265.
106. Rutz M, Metzger J, Geliert T, Luppa P, Lipford GB, Wagner H, Bauer S Toll-like receptor 9 binds single-stranded CpG-DNA in a sequence-and pH-dependent manner. Eur J Immunol 2004, 34:2541-2550.
107. Cornelie S, Hoebeke J, Schacht AM, Bertin B, Vicogne J, Capron M, Riveau G Direct evidence that toll-like receptor 9 (TLR9) functionally binds plasmid DNA by specific cytosine-phosphate-guanine motif recognition. J Biol Chem 2004, 279:15124-15129.
108. Latz E, Schoenemeyer A, Visintin A, Fitzgerald KA, Monks BG, Knetter CF, Lien E, Nilsen NJ, Espevik T, Golenbock DT TLR9 signals after translocating from the ER to CpG DNA in the lysosome. Nat Immunol 2004, 5:190-198.
109. Roberts TL, Sweet MJ, Hume DA, Stacey KJ Cutting edge: species-specific TLR9-mediated recognition of CpG and non-CpG phospho-rothioate-modified oligonucleotides. J Immunol 2005, 174:605-608.
110. Bauer S, Kirschning CJ, Hacker H, Redecke V, Hausmann S, Akira S, Wagner H, Lipford GB Human TLR9 confers responsiveness to bacte-rial DNA via species-specific CpG motif recognition. Proc Natl Acad Sci U S A 2001, 98:9237-9242.
111. Abel K, Wang Y, Fritts L, Sanchez E, Chung E, Fitzgerald-Bocarsly P, Krieg AM, Miller CJ Deoxycytidyl-deoxyguanosine oligonucleotide classes A B, and C induce distinct cytokine gene expression patterns in rhesus monkey peripheral blood mononuclear distinct alpha interferon responses in TLR9-expressing rhesus monkey plasmacytoid dendritic cells. Clin Diagn Lab Immunol 2005, 12:606-621.
112. Kandimalla ER, Bhagat L, Li Y, Yu D, Wang D, Cong YP, Song SS, Tang JX, Sullivan T, Agrawal S Immunomodulatory oligonucleotides containing a cytosine-phosphate-2′-deoxy-7-deazaguanosine motif as potent toll-like receptor 9 agonists. Proc Natl Acad Sci USA 2005, 102:6925-6930.
113. Hacker H, Vabulas RM, Takeuchi O, Hoshino K, Akira S, Wagner H Immune cell activation by bacterial CpG-DNA through myeloid differentiation marker 88 and tumor necrosis factor receptor-associated factor (TRAF) 6. J Exp Med 2000, 192:595-600.
114. Kawai T, Sato S, Ishii KJ, Coban C, Hemmi H, Yamamoto M, Terai K, Matsuda M, Inoue J, Uematsu S, Takeuchi O, Akira S Interferon-alpha induction through Toll-like receptors involves a direct interac-tion of IRF7 with MyD88 and TRAF6. Nat Immunol 2004, 5:1061-1068.
115. Uematsu S, Sato S, Yamamoto M, Hirotani T, Kato H, Takeshita F, Matsuda M, Coban C, Ishii KJ, Kawai T, Takeuchi O, Akira S Interleukin-1 receptor-associated kinase-1 plays an essential role for Toll-like receptor (TLR) 7-and TLR9-mediated interferonα induc-tion. J Exp Med 2005, 201:915-923.
116. Akhtar M, Watson JL, Nazli A, McKay DM Bacterial DNA evokes epithelial IL-8 production by a MAPK-dependent NF-kappaB-independent pathway. FASEB J 2003, 17:1319-1321.
117. Jijon H, Backer J, Diaz H, Yeung H, Thiel D, McKaigney C, De Simone C, Madsen K DNA from probiotic bacteria modulates murine and human epithelial and immune function. Gastroenterology 2004, 126:1358-1373.
118. Honda K, Yanai H, Negishi H, Asagiri M, Sato M, Mizutani T, Shimada N, Ohba Y, Takaoka A, Yoshida N, Taniguchi T IRF-7 is the master regulator of type-I interferon-dependent immune responses. Nature 2005, 434:772-777.
119. Blackwell SE, Krieg AM CpG-A-induced monocyte IFN-gamma-inducible protein-10 production is regulated by plasmacytoid dendritic cell-derived IFN-alpha. J Immunol 2003, 170:4061-4068.
120. Bauer M, Redecke V, Ellwart JW, Scherer B, Kremer JP, Wagner H, Lipford GB Bacterial CpG-DNA triggers activation and maturation of human CD11c-, CD123+ dendritic cells. J Immunol 2001, 166:5000-5007.
121. Napolitani G, Rinaldi A, Bertoni F, Sallusto F, Lanzavecchia A Selected Toll-like receptor agonist combinations synergistically trigger a T helper type 1-polarizing program in dendritic cells. Nat Immunol 2005, 6:769-776.
122. Hartmann G, Weiner GJ, Krieg AM CpG DNA: a potent signal for growth activation and maturation of human dendritic cells. Proc Natl Acad Sci USA 1999, 96:9305-9310.
123. Cowdery JS, Chace JH, Yi AK, Krieg AM Bacterial DNA induces NK cells to produce IFN-gamma in vivo and increases the toxicity of lipopolysaccharides. J Immunol 1996, 156:4570-4575.
124. Klinman DM, Yi AK, Beaucage SL, Conover J, Krieg AM CpG motifs present in bacteria DNA rapidly induce lymphocytes to secrete interleukin 6 interleukin 12 and interferon gamma. Proc Natl Acad Sci U S A 1996, 93:2879-2883.
125. Yi AK, Chang M, Peckham DW, Krieg AM, Ashman RF CpG oligodeoxyribonucleotides rescue mature spleen B cells from sponta-neous apoptosis and promote cell cycle entry. J Immunol 1998, 160:5898-5906.
126. Krieg AM, Yi AK, Matson S, Waldschmidt TJ, Bishop GA, Teasdale R, Koretzky GA, Klinman DM CpG motifs in bacterial DNA trigger direct B-cell activation. Nature 1995, 374:546-549.
127. Goeckeritz BE, Flora M, Witherspoon K, Vos Q, Lees A, Dennis GJ, Pisetsky DS, Klinman DM, Snapper CM, Mond JJ Multivalent crosslinking of membrane Ig sensitizes murine B cells to a broader spectrum of CpG-containing oligodeoxynucleotide motifs, including their methyla counterparts, for stimulation of proliferation and Ig secretion. Int Immunol 1999, 11:1693-1700.
128. Chu RS, Targoni OS, Krieg AM, Lehmann PV, Harding CV CpG oligodeoxynucleotides act as adjuvants that switch on T helper 1 (Th1) immunity. J Exp Med 1997, 186:1623-1631.
129. Sparwasser T, Vabulas RM, Villmow B, Lipford GB, Wagner H Bacterial CpG-DNA activates dendritic cells in vivo: T helper cell-independent cytotoxic T cell responses to soluble proteins. Eur J Immunol 2000, 30:3591-3597.
130. Krieg AM, Love-Homan L, Yi AK, Harty JT CpG DNA induces sustained IL-12 expression in vivo and resistance to Listeria monocy-togenes challenge. J Immunol 1998, 161:2428-2434.
131. Klinman DM, Conover J, Coban C Repeated administration of synthetic oligodeoxynucleotides expressing CpG motifs provides long-term protection against bacterial infection. Infect Immun 1999, 67:5658-5663.
132. Tabeta K, Georgel P, Janssen E, Du X, Hoebe K, Crozat K, Mudd S, Shamel L, Sovath S, Goode J, Alexopoulou L, Flavell RA, Beutler B Toll-like receptors 9 and 3 as essential components of innate immune defense against mouse cytomegalovirus infection. Proc Natl Acad Sci U S A 2004, 101:3516-3521.
133. Krug A, French AR, Barchet W, Fischer JA, Dzionek A, Pingel JT, Orihuela MM, Akira S, Yokoyama WM, Colonna M TLR9-dependent recognition of MCMV by IPC and DC generates coordinated cytokine responses that activate antiviral NK cell function. Immunity 2004, 21:107-119.
134. Edwards L, Williams AE, Krieg AM, Rae AJ, Snelgrove RJ, Hussell T Stimulation via Toll-like receptor 9 reduces Cryptococcus neoformans-induced pulmonary inflammation in an IL-12-dependent manner. Eur J Immunol 2005, 35:273-281.
135. Horner AA, Ronaghy A, Cheng PM, Nguyen MD, Cho HJ, Broide D, Raz E Immunostimulatory DNA is a potent mucosal adjuvant. Cell Immunol 1998, 190:77-82.
136. Horner AA, Datta SK, Takabayashi K, Belyakov IM, Hayashi T, Cinman N, Nguyen MD, Van Uden JH, Berzofsky JA, Richman DD, Raz E Immunostimulatory DNA-based vaccines elicit multifaceted immune responses against HIV at systemic and mucosal sites. J Immunol 2001, 167:1584-1591.
137. Rachmilewitz D, Karmeli F, Takabayashi K, Hayashi T, Leider-Trejo L, Lee J, Leoni LM, Raz E Immunostimulatory DNA ameliorates exper-imental and spontaneous murine colitis. Gastroenterology 2002, 122:1428-1441.
138. Obermeier F, Dunger N, Strauch UG, Grunwald N, Herfarth H, Scholmerich J Falk W Contrasting activity of cytosin-guanosin dinu-cleotide oligonucleotides in mice with experimental colitis. Clin Exp Immunol 2003, 134:217-224.
139. Obermeier F, Dunger N, Deml L, Herfarth H, Scholmerich J Falk W CpG motifs of bacterial DNA exacerbate colitis of dextran sulfate sodium-treated mice. Eur J Immunol 2002, 32:2084-2092.
140. Katakura K, Lee J, Rachmilewitz D, Li G, Eckmann L, Raz E Toll-like receptor 9-induced type I IFN protects mice from experimental colitis. J Clin Invest 2005, 115:695-702.
141. Obermeier F, Strauch UG, Dunger N, Grunwald N, Rath HC, Herfarth HH, Scholmerich J, Falk W Vivo CpG DNA/toll-like receptor 9 interaction induces regulatory properties in CD4+CD62L+ T cells which prevent intestinal inflammation in the SCID transfer model of colitis. Gut 2005, 54:1428-1436.
142. Heikenwalder M, Polymenidou M, Junt T, Sigurdson C, Wagner H, Akira S, Zinkernagel R, Aguzzi A Lymphoid follicle destruction and immunosuppression after repeated CpG oligodeoxynucleotide administration. Nat Med 2004, 10:187-192.
143. Krug A, Luker GD, Barchet W, Leib DA, Akira S, Colonna M Herpes simplex virus type 1 activates murine natural interferon-producing cells through toll-like receptor 9. Blood 2004, 103:1433-1437.
144. Hochrein H, Schlatter B, O'Keeffe M, Wagner C, Schmitz F, Schiemann M, Bauer S, Suter M, Wagner H Herpes simplex virus type-1 induces IFN-alpha production via Toll-like receptor 9-dependent and-independent pathways. Proc Natl Acad Sci USA 2004, 101:11416-11421.
145. Bambou JC, Giraud A, Menard S, Begue B, Rakotobe S, Heyman M, Taddei F, Cerf-Bensussan N, Gaboriau-Routhiau V In vitro and ex vivo activation of the TLR5 signaling pathway in intestinal epithelial cells by a commensal Escherichia coli strain. J Biol Chem 2004, 279:42984-42992.
146. Maaser C, Heidemann J, von EiffC, Lugering A, Spahn TW, Binion DG, Domschke W, Lugering N, Kucharzik T Human intestinal microvascular endothelial cells express Toll-like receptor 5: a binding partner for bacterial flagellin. J Immunol 2004, 172:5056-5062.
147. Hayashi F, Smith KD, Ozinsky A, Hawn TR, Yi EC, Goodlett DR, Eng JK, Akira S, Underhill DM, Aderem A The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 2001, 410:1099-1103.
148. Smith KD, Andersen-Nissen E, Hayashi F, Strobe K, Bergman MA, Barrett SL, Cookson BT, Aderem A Toll-like receptor 5 recognizes a conserved site on flagellin required for protofilament formation and bacterial motility. Nat Immunol 2003, 4:1247-1253.
149. West AP, Dancho BA, Mizel SB Gangliosides inhibit flagellin signaling in the absence of an effect on flagellin binding to toll-like receptor 5. J Biol Chem 2005, 280:9482-9488.
150. Yu Y, Zeng H, Lyons S, Carlson A, Merlin D, Neish AS, Gewirtz AT TLR5-mediated activation of p38 MAPK regulates epithelial IL-8 expression via posttranscriptional mechanism. Am J Physiol Gastrointest Liver Physiol 2003, 285:G282-G290.
151. Rhee SH, Keates AC, Moyer MP, Pothoulakis C MEK is a key modu-lator for TLR5-induced interleukin-8 and MIP3alpha gene expression in non-transformed human colonic epithelial cells. J Biol Chem 2004, 279:25179-25188.
152. Gewirtz AT, Navas TA, Lyons S, Godowski PJ, Madara JL Cutting edge: bacterial flagellin activates basolaterally expressed TLR5 to induce epithelial proinflammatory gene expression. J Immunol 2001, 167:1882-1885.
153. Berin MC, Darfeuille-Michaud A, Egan LJ, Miyamoto Y, KagnoffMF Role of EHEC O157:H7 virulence factors in the activation of intes-tinal
154. Lyons S, Wang L, Casanova JE, Sitaraman SV, Merlin D, Gewirtz AT Salmonella typhimurium transcytoses flagellin via an SPI2-mediated vesicular transport pathway. J Cell Sci 2004, 117:5771-5780.
155. Mizel SB, Snipes JA Gram-negative flagellin-induced self-tolerance is associated with a block in interleukin-1 receptor-associated kinase release from toll-like receptor 5. J Biol Chem 2002, 277:22414-22420.
156. Gewirtz AT, Yu Y, Krishna US, Israel DA, Lyons SL, Peek RM Helicobacter pylori flagellin evades toll-like receptor 5-mediated innate immunity. J Infect Dis 2004, 189:1914-1920.
157. Andersen-Nissen E, Smith KD, Strobe KL, Barrett SL, Cookson BT, Logan SM, Aderem A Evasion of Toll-like receptor 5 by flagellated bacteria. Proc Natl Acad Sci USA 2005, 102:9247-9252.
158. McSorley SJ, Ehst BD, Yu Y, Gewirtz AT Bacterial flagellin is an effec-tive adjuvant for CD4+ T cells in vivo. J Immunol 2002, 169:3914-3919.
159. Means TK, Hayashi F, Smith KD, Aderem A, Luster AD The Toll-like receptor 5 stimulus bacterial flagellin induces maturation and chemokine production in human dendritic cells. J Immunol 2003, 170:5165-5175.
160. Sitaraman SV, Klapproth JM, Moore DA, Landers C, Targan S, Williams IR, Gewirtz AT Elevated flagellin-specific immunoglobulins in Crohn's disease. Am J Physiol Gastrointest Liver Physiol 2005, 288:G403-G406.
161. Lodes MJ, Cong Y, Elson CO, Mohamath R, Landers CJ, Targan SR, Fort M, Hershberg RM Bacterial flagellin is a dominant antigen in Crohn disease. J Clin Invest 2004, 113:1296-1306.
162. Hawn TR, Verbon A, Lettinga KD, Zhao LP, Li SS, Laws RJ, Skerrett SJ, Beutler B, Schroeder L, Nachman A, Ozinsky A, Smith KD, Adarem A A common dominant TLR5 stop codon polymorphism abolishes flagellin signaling and is associated with susceptibility to Legionnaires' disease. J Exp Med 2003, 198:1563-1572.
163. Dunstan SJ, Hawn TR, Hue NT, Parry CP, Ho VA, Vinh H, Diep TS, House D, Wain J, Aderem A, Hien TT, Farrar JJ Host susceptibility and clinical outcomes in toll-like receptor 5-deficient patients with typhoid fever in Vietnam. J Infect Dis 2005, 191:1068-1071.
164. Kadowaki N, Ho S, Antonenko S, Malefyt RW, Kastelein RA, Bazan F, Liu YJ Subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens. J Exp Med 2001, 194:863-869.
165. Muzio M, Bosisio D, Polentarutti N, D'Amico G, Stoppacciaro A, Mancinelli R, van't Veer C, Penton-Rol G, Ruco LP, Allavena P, Mantovani A Differential expression and regulation of toll-like recep-tors (TLR) in human leukocytes: selective expression of TLR3 in dendritic cells. J Immunol 2000, 164:5998-6004.
166. Matsumoto M, Funami K, Oshiumi H, Seya T Toll-like receptor 3: a link between toll-like receptor interferon and viruses. Microbiol Immunol 2004, 48:147-154.
167. Furrie E, Macfarlane S, Thomson G, Macfarlane GT Toll-like recep-tors-2-3 and-4 expression patterns on human colon and their regula-tion by mucosal-associated bacteria. Immunology 2005, 115:565-574.
168. Alexopoulou L, Holt AC, Medzhitov R, Flavell RA Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 2001, 413:732-738.
169. Kariko K, Ni H, Capodici J, Lamphier M, Weissman D mRNA is an endogenous ligand for Toll-like receptor 3. J Biol Chem 2004, 279:12542-12550.
170. Vijay-Kumar M, Gentsch JR, Kaiser WJ, Borregaard N, Offermann MK, Neish AS, Gewirtz AT Protein kinase R mediates intestinal epithelial gene remodeling in response to double-stranded RNA and live rotavirus. J Immunol 2005, 174:6322-6331.
171. Oshiumi H, Matsumoto M, Funami K, Akazawa T, Seya T TICAM-1 an adaptor molecule that participates in Toll-like receptor 3-mediated interferon-beta induction. Nat Immunol 2003, 4:161-167.
172. Guillot L, Le Goffic R, Bloch S, Escriou N, Akira S, Chignard M, Si-Tahar M Involvement of toll-like receptor 3 in the immune response of lung epithelial cells to double-stranded RNA and influenza A virus. J Biol Chem 2005, 280:5571-5580.
173. Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T, Miyagishi M, Taira K, Akira S, Fujita T The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol 2004, 5:730-737.
174. Li K, Foy E, Ferreon JC, Nakamura M, Ferreon AC, Ikeda M, Ray SC, Gale M, Lemon SM Immune evasion by hepatitis C virus NS3/4A protease-mediated cleavage of the Toll-like receptor 3 adaptor protein TRIE. Proc Natl Acad Sci U S A 2005, 102:2992-2997.
175. Edelmann KH, Richardson-Burns S, Alexopoulou L, Tyler KL, Flavell RA, Oldstone MB Does Toll-like receptor 3 play a biological role in virus infections?. Virology 2004, 322:231-238.
176. Schroder M, Bowie AG TLR3 in antiviral immunity: key player or bystander?. Trends Immunol 2005, 26:462-468.
177. Datta SK, Redecke V, Prilliman KR, Takabayashi K, Corr M, Tallant T, DiDonato J, Dziarski R, Akira S, Schoenberger SP, Raz E A subset of Toll-like receptor ligands induces cross-presentation by bone marrow-derived dendritic cells. J Immunol 2003, 170:4102-4110.
178. Schulz O, Diebold SS, Chen M, Naslund TI, Nolte MA, Alexopoulou L, Azuma YT, Flavell RA, Liljestrom P, Reise Sousa C Toll-like receptor 3 promotes cross-priming to virus-infected cells. Nature 2005, 433:887-892.
179. Lund JM, Alexopoulou L, Sato A, Karow M, Adams NC, Gale NW, Iwasaki A, Flavell RA Recognition of single-stranded RNA viruses by Toll-like receptor 7. Proc Natl Acad Sci U S A 2004, 101:5598-5603.
180. Heil F, Hemmi H, Hochrein H, Ampenberger F, Kirschning C, Akira S, Lipford G, Wagner H, Bauer S Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science 2004, 303:1526-1529.
181. Triantafilou K, Vakakis E, Orthopoulos G, Ahmed MA, Schumann C, Lepper PM, Triantafilou M TLR8 and TLR7 are involved in the host's immune response to human parechovirus 1. Eur J Immunol 2005, 35:2416-2423.
182. Triantafilou K, Orthopoulos G, Vakakis E, Ahmed MA, Golenbock DT, Lepper PM, Triantafilou M Human cardiac inflammatory responses triggered by Coxsackie B viruses are mainly Toll-like receptor (TLR) 8-dependent. Cell Microbiol 2005, 7:1117-1126.
183. Diebold SS, Kaisho T, Hemmi H, Akira S, Reise Sousa C Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 2004, 303:1529-1531.
184. Hasan U, Chaffois C, Gaillard C, Saulnier V, Merck E, Tancredi S, Guiet C, Briere F, Vlach J, Lebecque S, Trinchieri G, Bates EE Human TLR10 is a functional receptor, expressed by B cells and plasmacytoid dendritic cells, which activates gene transcription through MyD88. J Immunol 2005, 174:2942-2950.
185. Inohara N, Chamaillard M, McDonald C, Nunez G NOD-LRR proteins: role in host-microbial interactions and inflammatory disease. Annu Rev Biochem 2005, 74:355-383.
186. Ting JP, Davis BK CATERPILLER: a novel gene family important in immunity, cell death, and diseases. Annu Rev Immunol 2005, 23:387-414.
187. Nimchuk Z, Eulgem T, Holt BF, Dangl JL Recognition and response in the plant immune system. Annu Rev Genet 2003, 37:579-609.
188. Philpott DJ, Girardin SE The role of Toll-like receptors and Nod proteins in bacterial infection. Mol Immunol 2004, 41:1099-1108.
189. Inohara N, Koseki T, del Peso L, Hu Y, Yee C, Chen S, Carrio R, Merino J, Liu D, Ni J, Nunez G Nodi an Apaf-1-like activator of caspase-9 and nuclear factor-kappaB. J Biol Chem 1999, 274:14560-14567.
190. Hisamatsu T, Suzuki M, Podolsky DK Interferon-gamma augments CARD4/NOD1 gene and protein expression through interferon regu-latory factor-1 in intestinal epithelial cells. J Biol Chem 2003, 278:32962-32968.
191. Kim JG, Lee SJ KagnoffMR Nodl is an essential signal transducer in intestinal epithelial cells infected with bacteria that avoid recognition by toll-like receptors. Infect Immun 2004, 72:1487-1495.
192. Viala J, Chaput C, Boneca IG, Cardona A, Girardin SE, Moran AP, Athman R, Memet S, Huerre MR, Coyle AJ, DiStefano PS, Sansonetti PJ, Labigne A, Bertin J, Philpott DJ, Ferrero RL Nodl responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island. Nat Immunol 2004, 5:1166-1174.
193. Girardin SE, Boneca IG, Carneiro LA, Antignac A, Jehanno M, Viala J, Tedin K, Taha MK, Labigne A, Zahringer U, Coyle AJ, DiStefano PS, Berlin J, Sausonetti PJ, Philpott DJ Nodl detects a unique muropep-tide from gram-negative bacterial peptidoglycan. Science 2003, 300:1584-1587.
194. Chamaillard M, Hashimoto M, Horie Y, Masumoto J, Qiu S, Saab L, Ogura Y, Kawasaki A, Fukase K, Kusumoto S, Valvano MA, Foster SJ, Mak TW, Nunez G, Inohara N An essential role for NOD1 in host recognition of bacterial peptidoglycan containing diaminopimelic acid. Nat Immunol 2003, 4:702-707.
195. Girardin SE, Travassos LH, Herve M, Blanot D, Boneca IG, Philpott DJ, Sansonetti PJ, Mengin-Lecreulx D Peptidoglycan molecular require-ments allowing detection by Nodl and Nod2. J Biol Chem 2003, 278:41702-41708.
196. Yoo NJ, Park WS, Kim SY, Reed JC, Son SG, Lee JY, Lee SH Nod 1 a CARD protein. Biochem Biophys Res Commun 2002, 299:652-658. ances pro-interleukin-1beta processing through the interaction with pro-caspase-1.
197. Girardin SE, Tournebize R, Mavris M, Page AL, Li X, Stark GR, Bertin J, DiStefano PS, Yaniv M, Sansonetti PJ, Philpott DJ CARD4/Nod1 mediates NF-kappaB and JNK activation by invasive Shigella flexneri. EMBO Rep 2001, 2:736-742.
198. Crabtree JE, Wyatt JI, Trejdosiewicz LK, Peichl P, Nichols PH, Ramsay N, Primrose JN, Lindley IJ Interleukin-8 expression in Helicobacter pylori infected normal and neoplastic gastroduodenal mucosa. J Clin Pathol 1994, 47:61-66.
199. Cole SP, Cirillo D, KagnoffMF, Guiney DG, Eckmann L Coccoid and spiral Helicobacter pylori differ in their abilities to adhere to gastric epithelial cells and induce interleukin-8 secretion. Infect Immun 1997, 65:843-846.
200. Ogura Y, Inohara N, Benito A, Chen FF, Yamaoka S, Nunez G Nod2 A Nod1/Apaf-1 family member that is restricted to monocytes and activates NF-kappaB. J Biol Chem 2001, 276:4812-4818.
201. Ogura Y, Lala S, Xin W, Smith E, Dowds TA, Chen FF, Zimmermann E, Tretiakova M, Cho JH, Hart J, Greenson JK, Keshav S, Nunez G Expression of NOD2 in Paneth cells: a possible link to Crohn's ileitis. Gut 2003, 52:1591-1597.
202. Lala S, Ogura Y, Osborne C, Hor SY, Bromfield A, Davies S, Ogunbiyi O, Nunez G, Keshav S Crohn's disease and the NOD2 gene: a role for paneth cells. Gastroenterology 2003, 125:47-57.
203. Rosenstiel P, Fantini M, Brautigam K, Kuhbacher T, Waetzig GH, Seegert D, Schreiber S TNF-alpha and IFN-gamma regulate the expression of the NOD2 (CARD 15) gene in human intestinal epithelial cells. Gastroenterology 2003, 124:1001-1009.
204. Inohara N, Ogura Y, Fontalba A, Gutierrez O, Pons F, Crespo J, Fukase K, Inamura S, Kusumoto S, Hashimoto M, Foster SJ, Moran AP, Fernandez-Luna JL, Nunez G Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn's disease. J Biol Chem 2003, 278:5509-5512.
205. Girardin SE, Boneca IG, Viala J, Chamaillard M, Labigne A, Thomas G, Philpott DJ, Sansonetti PJ Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection. J Biol Chem 2003, 278:8869-8872.
206. Abbott DW, Wilkins A, Asara JM, Cantley LC The Crohn's disease protein NOD2, requires RIP2 in order to induce ubiquitinylation of a novel site on NEMO. Curr Biol 2004, 14:2217-2227.
207. Tanabe T, Chamaillard M, Ogura Y, Zhu L, Qiu S, Masumoto J, Ghosh P, Moran A, Predergast MM, Tromp G, Williams CJ, Inohara N, Nunez G Regulatory regions and critical residues of NOD2 involved in muramyl dipeptide recognition. EMBO J 2004, 23:1587-1597.
208. Barnich N, Hisamatsu T, Aguirre JE, Xavier R, Reinecker HC, Podolsky DK GRIM-19 interacts with NOD2 and serves as down-stream effector of anti-bacterial function in intestinal epithelial cells. J Biol Chem 2005, 280:19021-19026.
209. Fearnley IM, Carroll J, Shannon RJ, Runswick MJ, Walker JE, Hirst J GRIM-19, a cell death regulatory gene product, is a subunit of bovine mitochondrial NADH:ubiquinone oxidoreductase (complex I). J Biol Chem 2001, 276:38345-38348.
210. Zhang J, Yang J, Roy SK, Tininini S, Hu J, Bromberg JF, Poli V, Stark GR, Kalvakolanu DV The cell death regulator GRIM-19 is an inhibitor of signal transducer and activator of transcription 3. Proc Natl Acad Sci U S A 2003, 100:9342-9347.
211. Chen CM, Gong Y, Zhang M, Chen JJ Reciprocal cross-talk between Nod2 and TAK1 signaling pathways. J Biol Chem 2004, 279:25876-25882.
212. Takaesu G, Surabhi RM, Park KJ, Ninomiya-Tsuji J, Matsumoto K, Gaynor RB TAK1 is critical for IkappaB kinase-mediated activation of the NF-kappaB pathway. J Mol Biol 2003, 326:105-115.
213. Pauleau AL, Murray PJ Role of nod2 in the response of macrophages to toll-like receptor agonists. Mol Cell Biol 2003, 23:7531-7539.
214. Kobayashi KS, Chamaillard M, Ogura Y, Henegariu O, Inohara N, Nunez G, Flavell RA Nod2-dependent regulation of innate and adap-tive immunity in the intestinal tract. Science 2005, 307:731-734.
215. Hisamatsu T, Suzuki M, Reinecker HC, Nadeau WJ, McCormick BA, Podolsky DK CARD15/NOD2 functions as an antibacterial factor in human intestinal epithelial cells. Gastroenterology 2003, 124:993-1000.
216. Hugot JP, Chamaillard M, Zouali H, Lesage S, Cezard JP, Belaiche J, Aimer S, Tysk C, O'Morain CA, Gassull M, Binder V, Finkel Y, Cortot A, Modigliani R, Laurent-Puig P, Gower-Rousseau C, Macry J, Colombel JF, Sahbatou M, Thomas G Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 2001, 411:599-603.
217. Ogura Y, Bonen DK, Inohara N, Nicolae DL, Chen FF, Ramos R, Britton H, Moran T, Karaliuskas R, Duerr RH, Achkar JP, Brant SR, Bayless TM, Kirschner BS, Hanaver SB, Nunez G, Cho JH A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature 2001, 411:603-606.
218. Miceli-Richard C, Lesage S, Rybojad M, Prieur AM, Manouvrier-Hanu S, Hafner R, Chamaillard M, Zouali H, Thomas G, Hugot JP CARD15 mutations in Blau syndrome. Nat Genet 2001, 29:19-20.
219. Rahman P, Bartlett S, Siannis F, Pellett FJ, Farewell VT, Peddle L, Schentag CT, Alderdice CA, Hamilton S, Khraishi M, Tobin Y, Hefferton D, Gladman DD CARD15: a pleiotropic autoimmune gene that confers susceptibility to psoriatic arthritis. Am J Hum Genet 2003, 73:677-681.
220. Economou M, Trikalinos TA, Loizou KT, Tsianos EV, Ioannidis JP Differential effects of NOD2 variants on Crohn's disease risk and phenotype in diverse populations: a metaanalysis. Am J Gastroenterol 2004, 99:2393-2404.
221. Ahmad T, Armuzzi A, Bunce M, Mulcahy-Hawes K, Marshall SE, Orchard TR, Crawshaw J, Large O, de Silva A, Cook JT, Barnardo M, Cullen S, Welsh KI, Jewell DP The molecular classification of the clinical manifestations of Crohn's disease. Gastroenterology 2002, 122:854-866.
222. Plant D, Lear J, Marsland A, Worthington J, Griffiths CE CARD15/NOD2 single nucleotide polymorphisms do not confer susceptibility to type I psoriasis. Br J Dermatol 2004, 151:675-678.
223. Kurzawski G, Suchy J, Kladny J, Grabowska E, Mierzejewski M, Jakubowska A, Debniak T, Cybulski C, Kowalska E, Szych Z, Domagala W, Scott RJ, Lubinski J The NOD2 3020insC mutation and the risk of colorectal cancer. Cancer Res 2004, 64:1604-1606.
224. Huzarski T, Lener M, Domagala W, Gronwald J, Byrski T, Kurzawski G, Suchy J, Chosia M, Woyton J, Ucinski M, Narod SA, Lubinski J The 3020insC allele of NOD2 predisposes to early-onset breast cancer. Breast Cancer Res Treat 2005, 89:91-93.
225. Alhopuro P, Ahvenainen T, Mecklin JP, Juhola M, Jarvinen HJ, Karhu A, Aaltonen LA NOD2 3020insC alone is not sufficient for colorectal cancer predisposition. Cancer Res 2004, 64:7245-7247.
226. Netea MG, Kullberg BJ, de Jong DJ, Franke B, Sprong T, Naber TH, Drenth JP, Van der Meer JW NOD2 mediates anti-inflammatory signals induced by TLR2 ligands: implications for Crohn's disease. Eur J Immunol 2004, 34:2052-2059.
227. van Heel DA, Ghosh S, Butler M, Hunt KA, Lundberg AM, Ahmad T, McGovern DP, Onnie C, Negoro K, Goldthorpe S, Foxwell BM, Mathew CG, Forbes A, Jewell DP, Playford RJ Muramyl dipeptide and toll-like receptor sensitivity in NOD2-associated Crohn's disease. Lancet 2005, 365:1794-1796.
228. Rogler G, Brand K, Vogl D, Page S, Hofmeister R, Andus T, Knuechel R, Baeuerle PA, Scholmerich J Gross V Nuclear factor kappaB is acti-vated in macrophages and epithelial cells of inflamed intestinal mucosa. Gastroenterology 1998, 115:357-369.
229. Schreiber S, Nikolaus S, Hampe J Activation of nuclear factor kappa B inflammatory bowel disease. Gut 1998, 42:477-484.
230. Eckmann L Karin M. NOD2 and Crohn's disease: loss or gain of function? Immunity 2005, 22:661-667.
231. Watanabe T, Kitani A, Murray PJ, Strober W NOD2 is a negative regulator of Toll-like receptor 2-mediated T helper type 1 responses. Nat Immunol 2004, 5:800-808.
232. Bouma G, Strober W The immunological and genetic basis of inflam-matory bowel disease. Nat Rev Immunol 2003, 3:521-533.
233. Maeda S, Hsu LC, Liu H, Bankston LA, Iimura M, KagnoffMF, Eckmann L, Karin M Nod2 mutation in Crohn's disease potentiates NF-kappaB activity and IL-1beta processing. Science 2005, 307:734-738.
234. Bulet P, Stocklin R, Menin L Anti-microbial peptides: from inverte-brates to vertebrates. Immunol Rev 2004, 198:169-184.
235. Patil A, Hughes AL, Zhang G Rapid evolution and diversification of mammalian alpha-defensins as revealed by comparative analysis of rodent and primate genes. Physiol Genomics 2004, 20:1-11.
236. Hornef MW, Putsep K, Karlsson J, Refai E, Andersson M Increased diversity of intestinal antimicrobial peptides by covalent dimer forma-tion. Nat Immunol 2004, 5:836-843.
237. Cunliffe RN Alpha-defensins in the gastrointestinal tract. Mol Immunol 2003, 40:463-467.
238. Cunliffe RN, Rose FR, Keyte J, Abberley L, Chan WC, Mahida YR Human defensin 5 is stored in precursor form in normal Paneth cells and is expressed by some villous epithelial cells and by metaplastic Paneth cells in the c inflammatory bowel disease. Gut 2001, 48:176-185.
239. Cunliffe RN, Kamal M, Rose FR, James PD, Mahida YR Expression of antimicrobial neutrophil defensins in epithelial cells of active inflammatory bowel disease mucosa. J Clin Pathol 2002, 55:298-304.
240. Eisenhauer PB, Lehrer RI Mouse neutrophils lack defensins. Infect Immun 1992, 60:3446-3447.
241. Ghosh D, Porter E, Shen B, Lee SK, Wilk D, Drazba J, Yadav SP, Crabb JW, Ganz T, Bevins CL Paneth cell trypsin is the processing enzyme for human defensin-5. Nat Immunol 2002, 3:583-590.
242. Ayabe T, Satchell DP, Pesendorfer P, Tanabe H, Wilson CL, Hagen SJ, Ouellette AJ Activation of Paneth cell alpha-defensins in mouse small intestine. J Biol Chem 2002, 277:5219-5228.
243. Wilson CL, Ouellette AJ, Satchell DP, Ayabe T, Lopez-Boado YS, Stratman JL, Hultgren SJ, Matrisian LM, Parks WC Regulation of intestinal alpha-defensin activation by the metalloproteinase matrilysin in innate host defense. Science 1999, 286:113-117.
244. Salzman NH, Chou MM, de Jong H, Liu L, Porter EM Paterson Y Enteric salmonella infection inhibits Paneth cell antimicrobial peptide expression. Infect Immun 2003, 71:1109-1115.
245. Porter EM, van Dam E, Valore EV, Ganz T Broad-spectrum antimi-crobial activity of human intestinal defensin 5. Infect Immun 1997, 65:2396-2401.
246. Aley SB, Zimmerman M, Hetsko M, Selsted ME, Gillin FD Killing of Giardia lamblia by cryptdins and cationic neutrophil peptides. Infect Immun 1994, 62:5397-5403.
247. Daher KA, Selsted ME, Lehrer RI Direct inactivation of viruses by human granulocyte defensins. J Virol 1986, 60:1068-1074.
248. Eisenhauer PB, Harwig SS, Lehrer RI Cryptdins: antimicrobial defensins of the murine small intestine. Infect Immun 1992, 60:3556-3565.
249. Ayabe T, Satchell DP, Wilson CL, Parks WC, Selsted ME, Ouellette AJ Secretion of microbicidal alpha-defensins by intestinal Paneth cells in response to bacteria. Nat Immunol 2000, 1:113-118.
250. Chavakis T, Cines DB, Rhee JS, Liang OD, Schubert U, Hammes HP, Higazi AA, Nawroth PP, Preissner KT, Bdeir K Regulation of neovascularization by human neutrophil peptides (alpha-defensins): a link between inflammation and angiogenesis. FASEB J 2004, 18:1306-1308.
251. Lin PW, Simon PO, Gewirtz AT, Neish AS, Ouellette AJ, Madara JL, Lencer WI Paneth cell cryptdins act in vitro as apical paracrine regu-lators of the innate inflammatory response. J Biol Chem 2004, 279:19902-19907.
252. Salzman NH, Ghosh D, Huttner KM, Paterson Y, Bevins CL Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin. Nature 2003, 422:522-526.
253. Maxwell AI, Morrison GM, Dorin JR Rapid sequence divergence in mammalian beta-defensins by adaptive evolution. Mol Immunol 2003, 40:413-421.
254. O'Neil DA, Porter EM, Elewaut D, Anderson GM, Eckmann L, Ganz T, KagnoffMF Expression and regulation of the human beta-defensins hBD-1 and hBD-2 in intestinal epithelium. J Immunol 1999, 163:6718-6724.
255. Zaalouk TK, Bajaj-Elliott M, George JT McDonald V Differential regulation of beta-defensin gene expression during Cryptosporidium parvum infection. Infect Immun 2004, 72:2772-2779.
256. Wehkamp J, Harder J, Weichenthal M, Mueller O, Herrlinger KR, Fellermann K, Schroeder JM, Stange EF Inducible and constitutive beta-defensins are differentially expressed in Crohn's disease and ulcerative colitis. Inflamm Bowel Dis 2003, 9:215-223.
257. Harder J, Bartels J, Christophers E, Schroder JM Isolation char-acterization of human beta-defensin-3 a novel human inducible peptide antibiotic. J Biol Chem 2001, 276:5707-5713.
258. Fahlgren A, Hammarstrom S, Danielsson A, Hammarstrom ML beta-Defensin-3 and-4 in intestinal epithelial cells display increased mRNA expression in ulcerative colitis. Clin Exp Immunol 2004, 137:379-385.
259. Kao CY, Chen Y, Zhao YH, Wu R ORFeome-based search of airway epithelial cell-specific novel human [beta-defensin genes. Am J Respir Cell Mol Biol 2003, 29:71-80.
260. Singh PK, Jia HP, Wiles K, Hesselberth J, Liu L, Conway BA, Greenberg EP, Valore EV, Welsh MJ, Ganz T, Tack BF, McCray PB Production of beta-defensins by human airway epithelia. Proc Natl Acad Sci USA 1998, 95:14961-14966.
261. Morrison G, Kilanowski F, Davidson D, Dorin J Characterization of the mouse beta defensin 1 Defb 1 mutant mouse model. Infect Immun 2002, 70:3053-3060.
262. Moser C, Weiner DJ, Lysenko E, Bals R, Weiser JN, Wilson JM beta-Defensin 1 contributes to pulmonary innate immunity in mice. Infect Immun 2002, 70:3068-3072.
263. Biragyn A, Ruffini PA, Leifer CA, Klyushnenkova E, Shakhov A, Chertov O, Shirakawa AK, Farber JM, Segal DM, Oppenheim JJ, Kwak LW Toll-like receptor 4-dependent activation of dendritic cells by beta-defensin 2. Science 2002, 298:1025-1029.
264. Yang D, Chertov O, Bykovskaia SN, Chen Q, Buffo MJ, Shogan J, Anderson M, Schroder JM, Wang JM, Howard OM, Oppenheim JJ Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science 1999, 286:525-528.
265. Cole AM, Ganz T, Liese AM, Burdick MD, Liu L, Strieter RM Cutting edge: IFN-inducible ELR-CXC chemokines display defensin-like antimicrobial activity. J Immunol 2001, 167:623-627.
266. Yang D, Biragyn A, Hoover DM, Lubkowski J, Oppenheim JJ Multiple roles of antimicrobial defensins cathelicidins and eosinophil-derived neurotoxin in host defense. Annu Rev Immunol 2004, 22:181-215.
267. Park CH, Valore EV, Waring AJ, Ganz T Hepcidin, a urinary antimi-crobial peptide synthesized in the liver. J Biol Chem 2001, 276:7806-7810.
268. Krause A, Neitz S, Magert HJ, Schulz A, Forssmann WG, Schulz-Knappe P, Adermann K LEAP-1 a novel highly disulfide-bonded human peptide exhibits antimicrobial activity. FEBS Lett 2000, 480:147-150.
269. Krause A, Sillard R, Kleemeier B, Kluver E, Maronde E, Conejo-Garcia JR, Forssmann WG, Schulz-Knappe P, Nehls MC, Wattler F, Wattler S, Adermann K Isolation, biochemical characterization of LEAP-2 a novel blood peptide expressed in the liver. Protein Sci 2003, 12:143-152.
270. Ilyin G, Courselaud B, Troadec MB, Pigeon C, Alizadeh M, Leroyer P, Brissot P, Loreal O Comparative analysis of mouse hepcidin 1 and 2 genes: evidence for different patterns of expression and co-inducibility during iron overload. FEBS Lett 2003, 542:22-26.
271. Kemna E, Pickkers P, Nemeth E, van der Hoeven H, Swinkels D Time-course analysis of hepcidin serum iron and plasma cytokine levels in humans injected with LPS. Blood 2005, 106:1864-1866.
272. Kulaksiz H, Theilig F, Bachmann S, Gehrke SG, Rost D, Janetzko A, Cetin Y, Stremmel W The iron-regulatory peptide hormone hepcidin: expression and cellular localization in the mammalian kidney. J Endocrinol 2005, 184:361-370.
273. Pigeon C, Ilyin G, Courselaud B, Leroyer P, Turlin B, Brissot P, Loreal O A new mouse liver-specific gene encoding a protein homol-ogous to human antimicrobial peptide hepcidin is overexpressed during iron overload. J Biol Chem 2001, 276:7811-7819.
274. Nemeth E, Valore EV, Territo M, Schiller G, Lichtenstein A, Ganz T Hepcidin, a putative mediator of anemia of inflammation is a type II acute-phase protein. Blood 2003, 101:2461-2463.
275. Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S, Pedersen BK, Ganz T IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest 2004, 113:1271-1276.
276. Motley ST, Morrow BJ, Liu X, Dodge IL, Vitiello A, Ward CK, Shaw KJ Simultaneous analysis of host and pathogen interactions during an in vivo infection reveals local induction of host acute phase response proteins, a novel bac stress response, and evidence of a host-imposed metal ion limited environment. Cell Microbiol 2004, 6:849-865.
277. Nicolas G, Chauvet C, Viatte L, Danan JL, Bigard X, Devaux I, Beaumont C, Kahn A, Vaulont S The gene encoding the iron regulatory peptide hepcidin is regulated by anemia hypoxia and inflammation. J Clin Invest 2002, 110:1037-1044.
278. Nicolas G, Bennoun M, Devaux I, Beaumont C, Grandchamp B, Kahn A, Vaulont S Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice. Proc Natl Acad Sci U S A 2001, 98:8780-8785.
279. Roetto A, Papanikolaou G, Politou M, Alberti F, Girelli D, Christakis J, Loukopoulos D, Camaschella C Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis. Nat Genet 2003, 33:21-22.
280. Nicolas G, Bennoun M, Porteu A, Mativet S, Beaumont C, Grandchamp B, Sirito M, Sawadogo M, Kahn A, Vaulont S Severe iron deficiency anemia in transgenic mice expressing liver hepcidin. Proc Natl Acad Sci U S A 2002, 99:4596-4601.
281. Yamaji S, Sharp P, Ramesh B, Srai SK Inhibition of iron transport across human intestinal epithelial cells by hepcidin. Blood 2004, 104:2178-2180.
282. Ganz T Hepcidin - a regulator of intestinal iron absorption and iron recycling by macrophages. Best Pract Res Clin Haematol 2005, 18:171-182.
283. Rouault TA Microbiology Pathogenic bacteria prefer heme. Science 2004, 305:1577-1578.
284. Lehrer RI, Ganz T Cathelicidins: a family of endogenous antimicrobial peptides. Curr Opin Hematol 2002, 9:18-22.
285. Zanetti M Cathelicidins multifunctional peptides of the innate immunity. J Leukoc Biol 2004, 75:39-48.
286. Hase K, Eckmann L, Leopard JD, Varki N, KagnoffMF Cell differ-entiation is a key determinant of cathelicidin LL-37/human cationic antimicrobial protein 18 expression by human colon epithelium. Infect Immun 2002, 70:953-963.
287. Frohm M, Agerberth B, Ahangari G, Stahle-Backdahl M, Liden S, Wigzell H, Gudmundsson GH The expression of the gene coding for the antibacterial peptide LL-37 is induced in human keratinocytes during inflammatory disorders. J Biol Chem 1997, 272:15258-15263.
288. Hase K, Murakami M, Iimura M, Cole SP, Horibe Y, Ohtake T, Obonyo M, Gallo RL, Eckmann L, KagnoffMF Expression of LL-37 by human gastric epithelial cells as a potential host defense mecha-nism against Helicobacter pylori. G astro enterology 2003, 125:1613-1625.
289. Sorensen OE, Follin P, Johnsen AH, Calafat J, Tjabringa GS, Hiemstra PS, Borregaard N Human cathelicidin hCAP-18 is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3. Blood 2001, 97:3951-3959.
290. Murakami M, Lopez-Garcia B, BraffM, Dorschner RA, Gallo RL Postsecretory processing generates multiple cathelicidins for enhanced topical antimicrobial defense. J Immunol 2004, 172:3070-3077.
291. Sorensen OE, Gram L, Johnsen AH, Andersson E, Bangsboll S, Tjabringa GS, Hiemstra PS, Malm J, Egesten A, Borregaard N Processing of seminal plasma hCAP-18 to ALL-38 by gastricsin: a novel mechanism of generating antimicrobial peptides in vagina. J Biol Chem 2003, 278:28540-28546.
292. Turner J, Cho Y, Dinh NN, Waring AJ, Lehrer RL Activities of LL-37 a cathelin-associated antimicrobial peptide of human neutrophils. Antimicrob Agents Chemother 1998, 42:2206-2214.
293. den Hertog AL, van Marie J, van Veen HA, Van't Hof W, Bolscher JG, Veerman EC Nieuw Amerongen AV Candidacidal effects of two antimicrobial peptides: histatin 5 causes small membrane defects but LL-37 causes massive disruption of the cel. Biochem J 2005, 388:689-695.
294. Henzler-Wildman KA, Martinez GV, Brown MF, Ramamoorthy A Perturbation of the hydrophobic core of lipid bilayers by the human antimicrobial peptide LL-37. Biochemistry 2004, 43:8459-8469.
295. Nizet V, Ohtake T, Lauth X, Trowbridge J, Rudisill J, Dorschner RA, Pestonjamasp V, Piraino J, Huttner K, Gallo RL Innate antimicrobial peptide protects the skin from invasive bacterial infection. Nature 2001, 414:454-457.
296. Rosenberger CM, Gallo RL, Finlay BB Interplay between antibacterial effectors: a macrophage antimicrobial peptide impairs intracellular Salmonella replication. Proc Natl Acad Sci U S A 2004, 101:2422-2427.
297. Iimura M, Gallo RL, Hase K, Miyamoto Y, Eckmann L, KagnoffMF Cathelicidin mediates innate intestinal defense against colonization with epithelial adherent bacterial pathogens. J Immunol 2005, 174:4901-4907.
298. Koczulla R, von Degenfeld G, Kupatt C, Krotz F, Zahler S, Gloe T, Issbrucker K, Unterberger P, Zaiou M, Lebherz C, Karl A, Raake P, Pfosser A, Boekstegers P, Welsh U, Hiemstra PS, Vogelmeier C, Gallo RL, Clauss M, Bals R An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. 7 Clin Invest 2003, 111:1665-1672.
299. Davidson DJ, Currie AJ, Reid GS, Bowdish DM, MacDonald KL, Ma RC, Hancock RE, Speert DP The cationic antimicrobial peptide LL-37 modulates dendritic cell differentiation and dendritic cell-induced T cell polarization. J Immunol 2004, 172:1146-1156.
300. Tjabringa GS, Aarbiou J, Ninaber DK, Drijfhout JW, Sorensen OE, Borregaard N, Rabe KF, Hiemstra PS The antimicrobial peptide LL-37 activates innate immunity at the airway epithelial surface by transactivation of the epidermal growth factor receptor. J Immunol 2003, 171:6690-6696.
301. BraffMH, Hawkins MA, Di Nardo A, Lopez-Garcia B, Howell MD, Wong C, Lin K, Streib JE, Dorschner R, Leung DY, Gallo RL Structure-function relationships among human cathelicidin peptides: dissociation of antimicrobial properties from host immunostimulatory activities. J Immunol 2005, 174:4271-4278.
302. Elssner A, Duncan M, Gavrilin M, Wewers MD A novel P2X7 receptor activator, the human cathelicidin-derived peptide LL37, induces IL-1 beta processing and release. J Immunol 2004, 172:4987-4994.
303. Chung LP, Keshav S, Gordon S Cloning the human lysozyme cDNA: inverted Alu repeat in the mRNA and in situ hybridization for macrophages and Paneth cells. Proc Natl Acad Sci U S A 1988, 85:6227-6231.
304. Cross M, Mangelsdorf I, Wedel A, Renkawitz R Mouse lysozyme M gene: isolation characterization and expression studies. Proc Natl Acad Sci U S A 1988, 85:6232-6236.
305. Cortopassi GA, Wilson AC Recent origin of the P lysozyme gene in mice. Nucleic Acids Res 1990, 18:1911.
306. Fahlgren A, Hammarstrom S, Danielsson A, Hammarstrom ML Increased expression of antimicrobial peptides and lysozyme in colonic epithelial cells of patients with ulcerative colitis. Clin Exp Immunol 2003, 131:90-101.
307. Forsberg G, Fahlgren A, Horstedt P, Hammarstrom S, Hernell O, Hammarstrom ML Presence of bacteria and innate immunity of intestinal epithelium in childhood celiac disease. Am J Gastroenterol 2004, 99:894-904.
308. Masschalck B, Michiels CW Antimicrobial properties of lysozyme in relation to foodborne vegetative bacteria. Crit Rev Microbiol 2003, 29:191-214.
309. Cottagnoud P, Tomasz A Triggering of pneumococcal autolysis by lysozyme. J Infect Dis 1993, 167:684-690.
310. Pellegrini A, Thomas U, Bramaz N, Klauser S, Hunziker P, von Fellenberg R Identification and isolation of a bactericidal domain in chicken egg white lysozyme. J Appl Microbiol 1997, 82:372-378.
311. Ellison RT, Giehl TJ Killing of gram-negative bacteria by lacto-ferrin and lysozyme. J Clin Invest 1991, 88:1080-1091.
312. Ganz T, Gabayan V, Liao HI, Liu L, Oren A, Graf T, Cole AM Increased inflammation in lysozyme M-deficient mice in response to Micrococcus luteus and its peptidoglycan. Blood 2003, 101:2388-2392.
313. Akinbi HT, Epaud R, Bhatt H, Weaver TE Bacterial killing is enhanced by expression of lysozyme in the lungs of transgenic mice. J Immunol 2000, 165:5760-5766.
314. Chakraborti S Phospholipase A (2) isoforms: a perspective. Cell Signal 2003, 15:637-665.
315. Rouault M, Bollinger JG, Lazdunski M, Gelb MH, Lambeau G Novel mammalian group XII secreted phospholipase A2 lacking enzymatic activity. Biochemistry 2003, 42:11494-11503.
316. Capper EA, Marshall LA Mammalian phospholipases A (2): mediators of inflammation proliferation and apoptosis. Prog Lipid Res 2001, 40:167-197.
317. Huggins KW, Boileau AC, Hui DY Protection against diet-induced obesity and obesity-related insulin resistance in group 1B PLA2-defi-cient mice. Am J Physiol Endocrinol Metab 2002, 283:E994-E1001.
318. Qu XD, Lloyd KC, Walsh JH, Lehrer RI Secretion of type II phos-pholipase A2 and cryptdin by rat small intestinal Paneth cells. Infect Immun 1996, 64:5161-5165.
319. Haapamaki MM, Gronroos JM, Nurmi H, Alanen K, Kallajoki M, Nevalainen TJ Gene expression of group II phospholipase A2 in intestine in ulcerative colitis. Gut 1997, 40:95-101.
320. Haapamaki MM, Gronroos JM, Nurmi H, Alanen K, Nevalainen TJ Gene expression of group II phospholipase A2 in intestine in Crohn's disease. Am J Gastroenterol 1999, 94:713-720.
321. Buckland AG, Wilton DC The antibacterial properties of secreted phospholipases A (2). Biochim Biophys Acta 2000, 1488:71-82.
322. Koduri RS, Gronroos JO, Laine VJ, Le Calvez C, Lambeau G, Nevalainen TJ, Gelb MH Bactericidal properties of human murine groups III V X and XII secreted phospholipases A (2). J Biol Chem 2002, 277:5849-5857.
323. Dubouix A, Campanac C, Fauvel J, Simon MF, Salles JP, Roques C, Chap H, Marty N Bactericidal properties of group Ha secreted phos-pholipase A (2) against Pseudomonas aeruginosa clinical isolates. J Med Microbiol 2003, 52:1039-1045.
324. Weiss J, Inada M, Elsbach P, Crowl RM Structural determinants of the action against Escherichia coli of a human inflammatory fluid phospholipase A2 in concert with polymorphonuclear leukocytes. J Biol Chem 1994, 269:26331-26337.
325. Laine VJ, Grass DS, Nevalainen TJ Protection by group II phospholipase A2 against Staphylococcus aureus. J Immunol 1999, 162:7402-7408.
326. Laine VJ, Grass DS, Nevalainen TJ Resistance of transgenic mice expressing human group II phospholipase A2 to Escherichia coli infection. Infect Immun 2000, 68:87-92.
327. Strydom DJ The angiogenins. Cell Mol Life Sci 1998, 54:811-824.
328. Ganz T Angiogenin: an antimicrobial ribonuclease. Nat Immunol 2003, 4:213-214.
329. Hooper LV, Stappenbeck TS, Hong CV, Gordon JI Angiogenins: a new class of microbicidal proteins involved in innate immunity. Nat Immunol 2003, 4:269-273.
330. Etoh T, Shibuta K, Barnard GF, Kitano S, Mori M Angiogenin expression in human colorectal cancer: the role of focal macrophage infiltration. Clin Cancer Res 2000, 6:3545-3551.
331. Koutroubakis IE, Xidakis C, Karmiris K, Sfiridaki A, Kandidaki E, Kouroumalis EA Serum angiogenin in inflammatory bowel disease. Dig Dis Sci 2004, 49:1758-1762.
332. Tollin M, Bergman P, Svenberg T, Jornvall H, Gudmundsson GH, Agerberth B Antimicrobial peptides in the first line defence of human colon mucosa. Peptides 2003, 24:523-530.
333. Howell SJ, Wilk D, Yadav SP, Bevins CL Antimicrobial polypeptides of the human colonie epithelium. Peptides 2003, 24:1763-1770.
334. Hiemstra PS, van den Barselaar MT, Roest M, Nibbering PH, van Furth R Ubiquicidin a novel murine microbicidal protein present in the cytosolic fraction of macrophages. J Leukoc Biol 1999, 66:423-428.
335. Augusto LA, Decottignies P, Synguelakis M, Nicaise M, Le Marechal P, Chaby R Histones: a novel class of lipopolysaccharide-binding mole-cules. Biochemistry 2003, 42:3929-3938.
336. Rose FR, Bailey K, Keyte JW, Chan WC, Greenwood D, Mahida YR Potential role of epithelial cell-derived histone H1 proteins in innate antimicrobial defense in the human gastrointestinal tract. Infect Immun 1998, 66:3255-3263.
337. Fang FC Antimicrobial reactive oxygen and nitrogen species: concepts and controversies. Nat Rev Microbiol 2004, 2:820-832.
338. Alderton WK, Cooper CE, Knowles RG Nitric oxide synthases: structure function and inhibition. Biochem J 2001, 357:593-615.
339. Shah V, Lyford G, Gores G, Farrugia G Nitric oxide in gastrointesti-nal health and disease. Gastroenterology 2004, 126:903-913.
340. Huber A, Saur D, Kurjak M, Schusdziarra V, Allescher HD Characterization and splice variants of neuronal nitric oxide synthase in rat small intestine. Am J Physiol 1998, 275:G1146-G1156.
341. Hoffman RA, Zhang G, Nussler NC, Gleixner SL, Ford HR, Simmons RL, Watkins SC Constitutive expression of inducible nitric oxide synthase in the mouse ileal mucosa. Am J Physiol 1997, 272:G383-G392.
342. Murray IA, Daniels I, Coupland K, Smith JA, Long RG Increased activity and expression of iNOS in human duodenal enterocytes from patients with celiac disease. Am J Physiol Gastrointest Liver Physiol 2002, 283:G319-G326.
343. Singer II, Kawka DW, Scott S, Weidner JR, Mumford RA, Riehl TE Stenson WE Expression of inducible nitric oxide synthase and nitrotyrosine in colonie epithelium in inflammatory bowel disease. Gastroenterology 1996, 111:871-885.
344. Vazquez-Torres A, Jones-Carson J, Mastroeni P, Ischiropoulos H, Fang FC Antimicrobial actions of the NADPH phagocyte oxidase inducible nitric oxide synthase in experimental salmonellosis. I. Effects on microbial killing by activated peritoneal macrophages in vitro. J Exp Med 2000, 192:227-236.
345. Fang FC, Vazquez-Torres A Nitric oxide production by human macrophages: there's NO doubt about it. Am J Physiol Lung Cell Mol Physiol 2002, 282:L941-L943.
346. Salzman AL, Eaves-Pyles T, Linn SC, Denenberg AG, Szabo C Bacterial induction of inducible nitric oxide synthase in cultured human intestinal epithelial cells. Gastroenterology 1998, 114:93-102.
347. Witthoft T, Eckmann L, Kim JM, KagnoffMF Enteroinvasive bacte-ria directly activate expression of iNOS and NO production in human colon epithelial cells. Am J Physiol 1998, 275:G564-G571.
348. Vallance BA, Dijkstra G, Qiu B, van der Waaij LA, van Goor H, Jansen PL, Mashimo H, Collins SM Relative contributions of NOS isoforms during experimental colitis: endothelial-derived NOS main-tains mucosal integrity. Am J Physiol Gastrointest Liver Physiol 2004, 287:G865-G874.
349. MacMicking JD, Nathan C, Horn G, Chartrain N, Fletcher DS, Trumbauer M, Stevens K, Xie QW, Sokol K, Hutchinson N, Chen H, Mudgett JS Altered responses to bacterial infection and endotoxic shock in mice lacking inducible nitric oxide synthase. Cell 1985, 81:641-650.
350. Huang PL, Dawson TM, Bredt DS, Snyder SH, Fishman MC Targeted disruption of the neuronal nitric oxide synthase gene. Cell 1993, 75:1273-1286.
351. Huang PL, Huang Z, Mashimo H, Bloch KD, Moskowitz MA, Bevan JA, Fishman MC Hypertension in mice lacking the gene for endothelial nitric oxide synthase. Nature 1995, 377:239-242.
352. Takahashi T Pathophysiological significance of neuronal nitric oxide synthase in the gastrointestinal tract. J Gastroenterol 2003, 38:421-430.
353. McDonald KK, Zharikov S, Block ER, Kilberg MS A caveolar complex between the cationic amino acid transporter 1 and endothelial nitric-oxide synthase may explain the arginine paradox. J Biol Chem 1997, 272:31213-31216.
354. Lee J, Ryu H, Ferrante RJ, Morris SM, Ratan RR Translational control of inducible nitric oxide synthase expression by arginine can explain the arginine paradox. Proc Natl Acad Sci U S A 2003, 100:4843-4848.
355. Islam D, Veress B, Bardhan PK, Lindberg AA, Christensson B In situ characterization of inflammatory responses in the rectal mucosae of patients with shigellosis. Infect Immun 1997, 65:739-749.
356. Sobko T, Reinders C, Norin E, Midtvedt T, Gustafsson LE, Lundberg JO Gastrointestinal nitric oxide generation in germ-free and conventional rats. Am J Physiol Gastrointest Liver Physiol 2004, 287:G993-G997.
357. Nathan C, Shiloh MU Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens. Proc Natl Acad Sci U S A 2000, 97:8841-8848.
358. Schapiro JM, Libby SJ, Fang FC Inhibition of bacterial DNA replica-tion by zinc mobilization during nitrosative stress. Proc Natl Acad Sci U S A 2003, 100:8496-8501.
359. Mastroeni P, Vazquez-Torres A, Fang FC, Xu Y, Khan S, Hormaeche CE, Dougan G Antimicrobial actions of the NADPH phagocyte oxidase and inducible nitric oxide synthase in experimental salmonellosis. II. Effects on microbial proliferation survival in vivo. J Exp Med 2000, 192:237-248.
360. Vallance BA, Deng W, De Grado M, Chan C, Jacobson K, Finlay BB Modulation of inducible nitric oxide synthase expression by the attaching and effacing bacterial pathogen citrobacter rodentium in infected mice. Infect Immun 2002, 70:6424-6435.
361. Resta-Lenert S, Barrett KE Enteroinvasive bacteria alter barrier and transport properties of human intestinal epithelium: role of iNOS and COX-2. Gastroenterology 2002, 122:1070-1087.
362. Eckmann L, Laurent F, Langford TD, Hetsko ML, Smith JR, KagnoffMF, Gillin FD Nitric oxide production by human intestinal epithelial cells and competition for arginine as potential determinants of host defense against the lumen-dwelling Giardia lamblia. J Immunol 2000, 164:1478-1487.
363. Wilson KT, Xie Y, Musch MW, Chang EB Sodium nitroprusside stimulates anion secretion and inhibits sodium chloride absorption in rat colon. J Pharmacol Exp Ther 1993, 266:224-230.
364. Beck PL, Xavier R, Wong J, Ezedi I, Mashimo H, Mizoguchi A, Mizoguchi E, Bhan AK, Podolsky DK Paradoxical roles of different nitric oxide synthase isoforms in colonic injury. Am J Physiol Gastrointest Liver Physiol 2004, 286:G137-G147.