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Cited by 431Immune Response and InflammationGut microbiota and healthGastrointestinal motility and disorders

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Human Intestinal Epithelial Cells Are Broadly Unresponsive to Toll-Like Receptor 2-Dependent Bacterial Ligands: Implications for Host-Microbial Interactions in the Gut

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Melmed, Gil, Thomas, Lisa S, Lee, Nahee, Tesfay, Samuel Y, Lukasek, Katie, Michelsen, Kathrin S, Zhou, Yuehua, Hu, Bing, Arditi, Moshe, Abreu, Maria T·2003·The Journal of Immunology
DOI 10.4049/jimmunol.170.3.1406
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Abstract

Intestinal epithelial cells (IEC) interact with a high density of Gram-positive bacteria and are active participants in mucosal immune responses. Recognition of Gram-positive organisms by Toll-like receptor (TLR)2 induces proinflammatory gene expression by diverse cells. We hypothesized that IEC are unresponsive to Gram-positive pathogen-associated molecular patterns and sought to characterize the functional responses of IEC to TLR2-specific ligands. Human colonic epithelial cells isolated by laser capture microscopy and IEC lines (Caco-2, T84, HT-29) were analyzed for expression of TLR2, TLR6, TLR1, and Toll inhibitory protein (Tollip) mRNA by RT-PCR and quantitative real-time PCR. Response to Gram-positive bacterial ligands was measured by NF-κB reporter gene activation and IL-8 secretion. TLR2 protein expression was analyzed by immunofluorescence and flow cytometry. Colonic epithelial cells and lamina propria cells from both uninflamed and inflamed tissue demonstrate low expression of TLR2 mRNA compared with THP-1 monocytes. IECs were unresponsive to TLR2 ligands including the staphylococcal-derived Ags phenol soluble modulin, peptidoglycan, and lipotechoic acid and the mycobacterial-derived Ag soluble tuberculosis factor. Transgenic expression of TLR2 and TLR6 restored responsiveness to phenol soluble modulin and peptidoglycan in IEC. In addition to low levels of TLR2 protein expression, IEC also express high levels of the inhibitory molecule Tollip. We conclude that IEC are broadly unresponsive to TLR2 ligands secondary to deficient expression of TLR2 and TLR6. The relative absence of TLR2 protein expression by IEC and high level of Tollip expression may be important in preventing chronic proinflammatory cytokine secretion in response to commensal Gram-positive bacteria in the gut.

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Research works printed but not linked: 101

  1. 1998, J. Clin. Invest., 1815
  2. 1999, Am. J. Physiol., C351
  3. 1995, J. Immunol., 4147
  4. 1993, Gastroenterology, 1689
  5. 1995, J. Clin. Invest., 55
  6. 1994, Immunology, 505
  7. 1996, Infect. Immun., 4480
  8. 1997, Am. J. Physiol., C1160
  9. 1994, Immunology, 85
  10. 1991, Cell, 651
  11. 1995, Clin. Exp. Immunol., 448
  12. 2000, Infect. Immun., 1542
  13. 1991, Lancet, 771
  14. 1998, Inflamm. Bowel Dis., 29
  15. 1998, Gastroenterology, 398
  16. 2000, Cochrane Database Syst. Rev., CD001176
  17. 2000, Gastroenterology, 584
  18. 2000, Gastroenterology, 305
  19. 1999, Lancet, 635
  20. 1996, Am. J. Gastroenterol., 328
  21. 2000, Dig. Dis. Sci., 445
  22. 2000, Curr. Opin. Immunol., 226
  23. 1998, Infect. Immun., 5224
  24. 2000, Am. J. Gastroenterol., S19
  25. 1999, Gastroenterology, 310
  26. 2000, Inflamm. Bowel Dis., 116
  27. 2000, Gut, 162
  28. 2001, Infect. Immun., 2277
  29. 2001, J. Cell Biol., 705
  30. 2001, Nat. Immunol., 675
  31. 2000, J. Leukocyte Biol., 450
  32. 1999, J. Biol. Chem., 7611
  33. 2000, Nature, 111
  34. 2000, Trends Microbiol., 452
  35. 2001, Infect. Immun., 2270
  36. 1998, Science, 2085
  37. 2000, Curr. Opin. Immunol., 20
  38. 1999, J. Immunol., 3749
  39. 1999, J. Biol. Chem., 17406
  40. 1999, Immunity, 443
  41. 1999, J. Immunol., 1
  42. 1999, J. Biol. Chem., 33419
  43. 2001, J. Biol. Chem., 22041
  44. 2001, J. Immunol., 4074
  45. 2001, J. Leukocyte Biol., 1036
  46. 2000, J. Immunol., 5392
  47. 2000, Infect. Immun., 6398
  48. 2001, FEMS Immunol. Med. Microbiol., 53
  49. 1998, Nature, 284
  50. 2000, Proc. Natl. Acad. Sci. USA, 13766
  51. 2000, J. Endotoxin Res., 393
  52. 2001, J. Immunol., 15
  53. 1999, J. Immunol., 3920
  54. 2002, J. Immunol., 10
  55. 2000, J. Immunol., 7125
  56. 2002, Nat. Med., 878
  57. 2002, Eur. J. Immunol., 1182
  58. 2000, Nat. Cell Biol., 346
  59. 2001, J. Immunol., 987
  60. 2002, J. Biol. Chem., 7059
  61. 2001, Inflamm. Bowel Dis., 136
  62. 1999, Crit. Rev. Food Sci. Nutr., 13
  63. 2000, J. Nutr., 396S
  64. 1999, Appl. Environ. Microbiol., 5372
  65. 1999, Appl. Environ. Microbiol., 4799
  66. 1996, Gastroenterology, 1467
  67. 2000, Dig. Dis. Sci., 2091
  68. 2002, Am. J. Pathol., 2253
  69. 2002, Gastroenterology, A692
  70. 1998, J. Exp. Med., 855
  71. 2000, Infect. Immun., 7010
  72. 2002, Am. J. Pathol., 165
  73. 2001, J. Pediatr. Gastroenterol. Nutr., 449
  74. 2002, Gastroenterology, 1987
  75. 2000, Gastroenterology, 1524
  76. 1984, Am. J. Physiol., G204
  77. 1992, J. Invest. Dermatol., 683
  78. 2000, J. Biol. Chem., 11058
  79. 2001, Immunology, 49
  80. 2002, J. Immunol., 4531
  81. 2000, J. Immunol., 966
  82. 2001, J. Immunol., 2018
  83. 2001, J. Immunol., 1609
  84. 2001, J. Biol. Chem., 41350
  85. 2001, Nat. Immunol., 361
  86. 1997, Am. J. Respir. Crit. Care Med., 1157
  87. 1999, J. Urol., 1812
  88. 2002, J. Biol. Chem., 17263
  89. 2001, Pediatr. Res., 589
  90. 2001, J. Immunol., 2651
  91. 2002, J. Biol. Chem., 24315
  92. 2000, Gut, 350
  93. 1999, Am. J. Gastroenterol., 2923
  94. 2000, Inflamm. Bowel Dis., 206
  95. 1985, J. Cell Biol., 2124
  96. 1998, J. Clin. Invest., 2011
  97. 1999, Gastroenterology, 115
  98. 2001, J. Immunol., 7128
  99. 2001, J. Biol. Chem., 25680
  100. 2001, Eur. J. Immunol., 3131
  101. 2000, J. Immunol., 3804

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Metadata

Authors
Melmed, G., Thomas, L. S., Lee, N., Tesfay, S. Y., Lukasek, K., Michelsen, K. S., Zhou, Y., Hu, B., Arditi, M., & Abreu, M. T.
Affiliations
  • Cedars-Sinai Medical Center (US)
  • Inflammatory Bowel Disease Center, Division of Gastroenterology, Department of Medicine , Los Angeles, CA 90048
  • Division of Pediatric Infectious Diseases, Department of Pediatrics, Steven Spielberg Pediatric Research Center, Burns and Allen Research Institute , Los Angeles, CA 90048
Corresponding author
  • Melmed, Gil
  • Lee, Nahee
  • Lukasek, Katie
ORCID
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
2003-02-01
Volume
170
Issue
3
Pages
1406-1415
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
DOI
10.4049/jimmunol.170.3.1406
OpenAlex
W1902083634
Cited by
431
References
103
Citations by year
2026: 4 · 2025: 3 · 2024: 5 · 2023: 4 · 2022: 7 · 2021: 6 · 2020: 4 · 2019: 12 · 2018: 12 · 2017: 15 · 2016: 11 · 2015: 13 · 2014: 17 · 2013: 20 · 2012: 18
FWCI
12.15
Type
journal article
Language
en
Open access
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5k08dk002635-03, 5r29ai040275-02)
  • National Heart, Lung, and Blood Institute (HL66436, R01HL066436)
  • National Institute of Allergy and Infectious Diseases (AI-40275, R29 AI52266)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK02635)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords
TLR2, intestinal epithelial cells, Gram-positive bacteria, Tollip, TLR6, phenol-soluble modulins, peptidoglycan, lipoteichoic acid, NF-κB activation, IL-8 secretion, commensal bacteria, mucosal immunity, colonic epithelium, lamina propria, inflammatory cytokines
MeSH terms
Bacterial Toxins, Carrier Proteins, Cell Line, Gene Expression Regulation, Humans, Immune Tolerance, Intestinal Mucosa, Ligands, Lipopolysaccharides, Membrane Glycoproteins, Peptidoglycan, Receptors, Cell Surface, RNA, Messenger, Staphylococcus aureus, Staphylococcus epidermidis, Teichoic Acids, Transfection, Tumor Cells, Cultured, Signal Transduction, Transcriptional Activation, Caco-2 Cells, HT29 Cells, Transgenes, Drosophila Proteins, Intracellular Signaling Peptides and Proteins, Toll-Like Receptors, Toll-Like Receptor 1, Toll-Like Receptor 2, Toll-Like Receptor 6

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