| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Cutting Edge |
*
Epithelial Pathobiology Division, Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322; and
Department of Molecular Biology, Genentech, Inc., South San Francisco, CA 94080
Flagellin, the structural component of bacterial flagella, is
secreted by pathogenic and commensal bacteria. Flagellin activates
proinflammatory gene expression in intestinal epithelia. However, only
flagellin that contacts basolateral epithelial surfaces is
proinflammatory; apical flagellin has no effect. Pathogenic
Salmonella, but not commensal Escherichia
coli, translocate flagellin across epithelia, thus activating
epithelial proinflammatory gene expression. Investigating how epithelia
detect flagellin revealed that cell surface expression of Toll-like
receptor 5 (TLR5) conferred NF-
B gene expression in response to
flagellin. The response depended on both extracellular leucine-rich
repeats and intracellular Toll/IL-1R homology region of TLR5 as well as
the adaptor protein MyD88. Furthermore, immunolocalization and cell
surface-selective biotinylation revealed that TLR5 is expressed
exclusively on the basolateral surface of intestinal epithelia, thus
providing a molecular basis for the polarity of this innate immune
response. Thus, detection of flagellin by basolateral TLR5 mediates
epithelial-driven inflammatory responses to
Salmonella.
This article has been cited by other articles:
|
|
 |
|
  G. O. Canny and B. A. McCormick Bacteria in the Intestine, Helpful Residents or Enemies from Within? Infect. Immun., August 1, 2008; 76(8): 3360 - 3373. [Full Text] [PDF]
|
|
|
|
|
|
K. L. Mumy, J. D. Bien, M. A. Pazos, K. Gronert, B. P. Hurley, and B. A. McCormick Distinct Isoforms of Phospholipase A2 Mediate the Ability of Salmonella enterica Serotype Typhimurium and Shigella flexneri To Induce the Transepithelial Migration of Neutrophils Infect. Immun., August 1, 2008; 76(8): 3614 - 3627. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Janssen, K. A. Krogfelt, S. A. Cawthraw, W. van Pelt, J. A. Wagenaar, and R. J. Owen Host-Pathogen Interactions in Campylobacter Infections: the Host Perspective Clin. Microbiol. Rev., July 1, 2008; 21(3): 505 - 518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Vijay-Kumar, J. D. Aitken, C. J. Sanders, A. Frias, V. M. Sloane, J. Xu, A. S. Neish, M. Rojas, and A. T. Gewirtz Flagellin Treatment Protects against Chemicals, Bacteria, Viruses, and Radiation J. Immunol., June 15, 2008; 180(12): 8280 - 8285. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Sanders, D. A. Moore III, I. R. Williams, and A. T. Gewirtz Both Radioresistant and Hemopoietic Cells Promote Innate and Adaptive Immune Responses to Flagellin J. Immunol., June 1, 2008; 180(11): 7184 - 7192. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Chochi, T. Ichikura, M. Kinoshita, T. Majima, N. Shinomiya, H. Tsujimoto, T. Kawabata, H. Sugasawa, S. Ono, S. Seki, et al. Helicobacter pylori Augments Growth of Gastric Cancers via the Lipopolysaccharide-Toll-like Receptor 4 Pathway whereas Its Lipopolysaccharide Attenuates Antitumor Activities of Human Mononuclear Cells Clin. Cancer Res., May 15, 2008; 14(10): 2909 - 2917. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Echchannaoui, M. Bianchi, D. Baud, M. Bobst, J.-C. Stehle, and D. Nardelli-Haefliger Intravaginal Immunization of Mice with Recombinant Salmonella enterica Serovar Typhimurium Expressing Human Papillomavirus Type 16 Antigens as a Potential Route of Vaccination against Cervical Cancer Infect. Immun., May 1, 2008; 76(5): 1940 - 1951. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Yoon and J. J. Mekalanos Decreased Potency of the Vibrio cholerae Sheathed Flagellum To Trigger Host Innate Immunity Infect. Immun., March 1, 2008; 76(3): 1282 - 1288. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Ueno, T. Koga, K. Kato, D. T. Golenbock, S. J. Gendler, H. Kai, and K. C. Kim MUC1 Mucin Is a Negative Regulator of Toll-Like Receptor Signaling Am. J. Respir. Cell Mol. Biol., March 1, 2008; 38(3): 263 - 268. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. O. Petrof, M. W. Musch, M. Ciancio, J. Sun, M. E. Hobert, E. C. Claud, A. Gewirtz, and E. B. Chang Flagellin is required for salmonella-induced expression of heat shock protein Hsp25 in intestinal epithelium Am J Physiol Gastrointest Liver Physiol, March 1, 2008; 294(3): G808 - G818. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K Kojima, M Ueta, J Hamuro, Y Hozono, S Kawasaki, N Yokoi, and S Kinoshita Human conjunctival epithelial cells express functional Toll-like receptor 5 Br. J. Ophthalmol., March 1, 2008; 92(3): 411 - 416. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Johnson, X. Li, and E. Pearlman MyD88 Functions as a Negative Regulator of TLR3/TRIF-induced Corneal Inflammation by Inhibiting Activation of c-Jun N-terminal Kinase J. Biol. Chem., February 15, 2008; 283(7): 3988 - 3996. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. R. Ziegler, M. Luo, C. F. Estivariz, D. A. Moore III, S. V. Sitaraman, L. Hao, N. Bazargan, J.-M. Klapproth, J. Tian, J. R. Galloway, et al. Detectable serum flagellin and lipopolysaccharide and upregulated anti-flagellin and lipopolysaccharide immunoglobulins in human short bowel syndrome Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2008; 294(2): R402 - R410. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Berndt, A. Wilhelm, C. Jugert, J. Pieper, K. Sachse, and U. Methner Chicken Cecum Immune Response to Salmonella enterica Serovars of Different Levels of Invasiveness Infect. Immun., December 1, 2007; 75(12): 5993 - 6007. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-H. Sun, H. G. Rolan, and R. M. Tsolis Injection of Flagellin into the Host Cell Cytosol by Salmonella enterica Serotype Typhimurium J. Biol. Chem., November 23, 2007; 282(47): 33897 - 33901. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Chen, M. J. Cowan, J. D. Hasday, S. N. Vogel, and A. E. Medvedev Tobacco Smoking Inhibits Expression of Proinflammatory Cytokines and Activation of IL-1R-Associated Kinase, p38, and NF-{kappa}B in Alveolar Macrophages Stimulated with TLR2 and TLR4 Agonists J. Immunol., November 1, 2007; 179(9): 6097 - 6106. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R.-M. Salazar-Gonzalez, A. Srinivasan, A. Griffin, G. Muralimohan, J. M. Ertelt, R. Ravindran, A. T. Vella, and S. J. McSorley Salmonella Flagellin Induces Bystander Activation of Splenic Dendritic Cells and Hinders Bacterial Replication In Vivo J. Immunol., November 1, 2007; 179(9): 6169 - 6175. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Merlo, C. Calcaterra, S. Menard, and A. Balsari Cross-talk between Toll-like receptors 5 and 9 on activation of human immune responses J. Leukoc. Biol., September 1, 2007; 82(3): 509 - 518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kato, W. Lu, H. Kai, and K. C. Kim Phosphoinositide 3-kinase is activated by MUC1 but not responsible for MUC1-induced suppression of Toll-like receptor 5 signaling Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L686 - L692. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Ye, E. O. Petrof, D. Boone, E. C. Claud, and J. Sun Salmonella Effector AvrA Regulation of Colonic Epithelial Cell Inflammation by Deubiquitination Am. J. Pathol., September 1, 2007; 171(3): 882 - 892. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Nitcheu-Tefit, M.-S. Dai, R. J. Critchley-Thorne, F. Ramirez-Jimenez, M. Xu, S. Conchon, N. Ferry, H. J. Stauss, and G. Vassaux Listeriolysin O Expressed in a Bacterial Vaccine Suppresses CD4+CD25high Regulatory T Cell Function In Vivo J. Immunol., August 1, 2007; 179(3): 1532 - 1541. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Saha, F. Takeshita, T. Matsuda, N. Jounai, K. Kobiyama, T. Matsumoto, S. Sasaki, A. Yoshida, K.-Q. Xin, D. M. Klinman, et al. Blocking of the TLR5 Activation Domain Hampers Protective Potential of Flagellin DNA Vaccine J. Immunol., July 15, 2007; 179(2): 1147 - 1154. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A Mitchell, M. J Paul-Clark, G. W Clarke, S. K McMaster, and N. Cartwright Critical role of toll-like receptors and nucleotide oligomerisation domain in the regulation of health and disease J. Endocrinol., June 1, 2007; 193(3): 323 - 330. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Shinkai, Y. S. Lopez-Boado, and B. K. Rubin Clarithromycin has an immunomodulatory effect on ERK-mediated inflammation induced by Pseudomonas aeruginosa flagellin J. Antimicrob. Chemother., June 1, 2007; 59(6): 1096 - 1101. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Bogunovic, S. H. Dave, J. S. Tilstra, D. T. W. Chang, N. Harpaz, H. Xiong, L. F. Mayer, and S. E. Plevy Enteroendocrine cells express functional Toll-like receptors Am J Physiol Gastrointest Liver Physiol, June 1, 2007; 292(6): G1770 - G1783. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Karrasch, J.-S. Kim, M. Muhlbauer, S. T. Magness, and C. Jobin Gnotobiotic IL-10-/-;NF-{kappa}BEGFP Mice Reveal the Critical Role of TLR/NF-{kappa}B Signaling in Commensal Bacteria-Induced Colitis J. Immunol., May 15, 2007; 178(10): 6522 - 6532. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Schlee, J. Wehkamp, A. Altenhoefer, T. A. Oelschlaeger, E. F. Stange, and K. Fellermann Induction of Human {beta}-Defensin 2 by the Probiotic Escherichia coli Nissle 1917 Is Mediated through Flagellin Infect. Immun., May 1, 2007; 75(5): 2399 - 2407. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. Rawls, M. A. Mahowald, A. L. Goodman, C. M. Trent, and J. I. Gordon In vivo imaging and genetic analysis link bacterial motility and symbiosis in the zebrafish gut PNAS, May 1, 2007; 104(18): 7622 - 7627. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. T. Blikslager, A. J. Moeser, J. L. Gookin, S. L. Jones, and J. Odle Restoration of Barrier Function in Injured Intestinal Mucosa Physiol Rev, April 1, 2007; 87(2): 545 - 564. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Palazzo, A. Balsari, A. Rossini, S. Selleri, C. Calcaterra, S. Gariboldi, L. Zanobbio, F. Arnaboldi, Y. F. Shirai, G. Serrao, et al. Activation of Enteroendocrine Cells via TLRs Induces Hormone, Chemokine, and Defensin Secretion J. Immunol., April 1, 2007; 178(7): 4296 - 4303. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. K. Mayer, M. Muehmer, J. Mages, K. Gueinzius, C. Hess, K. Heeg, R. Bals, R. Lang, and A. H. Dalpke Differential Recognition of TLR-Dependent Microbial Ligands in Human Bronchial Epithelial Cells J. Immunol., March 1, 2007; 178(5): 3134 - 3142. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Sun, P. E. Fegan, A. S. Desai, J. L. Madara, and M. E. Hobert Flagellin-induced tolerance of the Toll-like receptor 5 signaling pathway in polarized intestinal epithelial cells Am J Physiol Gastrointest Liver Physiol, March 1, 2007; 292(3): G767 - G778. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Winkler, D. Ghadimi, J. Schrezenmeir, and J.-P. Kraehenbuhl Molecular and Cellular Basis of Microflora-Host Interactions J. Nutr., March 1, 2007; 137(3): 756S - 772S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. S. Steiner How Flagellin and Toll-Like Receptor 5 Contribute to Enteric Infection Infect. Immun., February 1, 2007; 75(2): 545 - 552. [Full Text] [PDF]
|
|
|
|
|
|
A. Srinivasan and S. J. McSorley Exposure to LPS suppresses CD4+ T cell cytokine production in Salmonella-infected mice and exacerbates murine typhoid J. Leukoc. Biol., February 1, 2007; 81(2): 403 - 411. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Neish TLRS in the Gut. II. Flagellin-induced inflammation and antiapoptosis Am J Physiol Gastrointest Liver Physiol, February 1, 2007; 292(2): G462 - G466. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. B. Vos, N. A. Datson, K. F. Rabe, and P. S. Hiemstra Exploring host-pathogen interactions at the epithelial surface: application of transcriptomics in lung biology Am J Physiol Lung Cell Mol Physiol, February 1, 2007; 292(2): L367 - L377. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. T. Dvorak, G. N. Hirsch, K. A. Hyland, J. A. Hendrickson, B. S. Thompson, M. S. Rutherford, and M. P. Murtaugh Genomic dissection of mucosal immunobiology in the porcine small intestine Physiol Genomics, December 13, 2006; 28(1): 5 - 14. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Xicohtencatl-Cortes, S. Lyons, A. P. Chaparro, D. R. Hernandez, Z. Saldana, M. A. Ledesma, M. A. Rendon, A. T. Gewirtz, K. E. Klose, and J. A. Giron Identification of Proinflammatory Flagellin Proteins in Supernatants of Vibrio cholerae O1 by Proteomics Analysis Mol. Cell. Proteomics, December 1, 2006; 5(12): 2374 - 2383. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Leifer, J. C. Brooks, K. Hoelzer, J. Lopez, M. N. Kennedy, A. Mazzoni, and D. M. Segal Cytoplasmic Targeting Motifs Control Localization of Toll-like Receptor 9 J. Biol. Chem., November 17, 2006; 281(46): 35585 - 35592. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. Du, F. Zhang, J. E. Capo-Aponte, S. D. Tachado, J. Zhang, F.-S. X. Yu, R. A. Sack, H. Koziel, and P. S. Reinach AsialoGM1-Mediated IL-8 Release by Human Corneal Epithelial Cells Requires Coexpression of TLR5 Invest. Ophthalmol. Vis. Sci., November 1, 2006; 47(11): 4810 - 4818. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Vijay-Kumar, H. Wu, R. Jones, G. Grant, B. Babbin, T. P. King, D. Kelly, A. T. Gewirtz, and A. S. Neish Flagellin Suppresses Epithelial Apoptosis and Limits Disease during Enteric Infection Am. J. Pathol., November 1, 2006; 169(5): 1686 - 1700. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Heidemann, W. Domschke, T. Kucharzik, and C. Maaser Intestinal microvascular endothelium and innate immunity in inflammatory bowel disease: a second line of defense? Infect. Immun., October 1, 2006; 74(10): 5425 - 5432. [Full Text] [PDF]
|
|
|
|
|
|
R. C. Alaniz, L. A. Cummings, M. A. Bergman, S. L. Rassoulian-Barrett, and B. T. Cookson Salmonella typhimurium Coordinately Regulates FliC Location and Reduces Dendritic Cell Activation and Antigen Presentation to CD4+ T cells J. Immunol., September 15, 2006; 177(6): 3983 - 3993. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Sanders, Y. Yu, D. A. Moore III, I. R. Williams, and A. T. Gewirtz Humoral immune response to flagellin requires T cells and activation of innate immunity. J. Immunol., September 1, 2006; 177(5): 2810 - 2818. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Feuillet, S. Medjane, I. Mondor, O. Demaria, P. P. Pagni, J. E. Galan, R. A. Flavell, and L. Alexopoulou Involvement of Toll-like receptor 5 in the recognition of flagellated bacteria PNAS, August 15, 2006; 103(33): 12487 - 12492. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Wakabayashi, M. Kobayashi, S. Akashi-Takamura, N. Tanimura, K. Konno, K. Takahashi, T. Ishii, T. Mizutani, H. Iba, T. Kouro, et al. A Protein Associated with Toll-Like Receptor 4 (PRAT4A) Regulates Cell Surface Expression of TLR4 J. Immunol., August 1, 2006; 177(3): 1772 - 1779. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Chun and A. Prince Activation of Ca2+-Dependent Signaling by TLR2 J. Immunol., July 15, 2006; 177(2): 1330 - 1337. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Johanesen and M. B. Dwinell Flagellin-Independent Regulation of Chemokine Host Defense in Campylobacter jejuni-Infected Intestinal Epithelium. Infect. Immun., June 1, 2006; 74(6): 3437 - 3447. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Romics Jr, G. Szabo, J. C. Coffey, J. H. Wang, and H. P. Redmond The Emerging Role of Toll-Like Receptor Pathways in Surgical Diseases Arch Surg, June 1, 2006; 141(6): 595 - 601. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. McNamara, M. Gallup, A. Sucher, I. Maltseva, D. McKemy, and C. Basbaum AsialoGM1 and TLR5 Cooperate in Flagellin-Induced Nucleotide Signaling to Activate Erk1/2 Am. J. Respir. Cell Mol. Biol., June 1, 2006; 34(6): 653 - 660. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. T. Gewirtz, M. Vijay-Kumar, S. R. Brant, R. H. Duerr, D. L. Nicolae, and J. H. Cho Dominant-negative TLR5 polymorphism reduces adaptive immune response to flagellin and negatively associates with Crohn's disease Am J Physiol Gastrointest Liver Physiol, June 1, 2006; 290(6): G1157 - G1163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Yu, S. Nagai, H. Wu, A. S. Neish, S. Koyasu, and A. T. Gewirtz TLR5-Mediated Phosphoinositide 3-Kinase Activation Negatively Regulates Flagellin-Induced Proinflammatory Gene Expression J. Immunol., May 15, 2006; 176(10): 6194 - 6201. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Prince Flagellar Activation of Epithelial Signaling Am. J. Respir. Cell Mol. Biol., May 1, 2006; 34(5): 548 - 551. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Lievin-Le Moal and A. L. Servin The Front Line of Enteric Host Defense against Unwelcome Intrusion of Harmful Microorganisms: Mucins, Antimicrobial Peptides, and Microbiota Clin. Microbiol. Rev., April 1, 2006; 19(2): 315 - 337. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Lu, A. Hisatsune, T. Koga, K. Kato, I. Kuwahara, E. P. Lillehoj, W. Chen, A. S. Cross, S. J. Gendler, A. T. Gewirtz, et al. Cutting Edge: Enhanced Pulmonary Clearance of Pseudomonas aeruginosa by Muc1 Knockout Mice J. Immunol., April 1, 2006; 176(7): 3890 - 3894. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Chabot, J. S. Wagner, S. Farrant, and M. R. Neutra TLRs Regulate the Gatekeeping Functions of the Intestinal Follicle-Associated Epithelium J. Immunol., April 1, 2006; 176(7): 4275 - 4283. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Sharma, S. Tesfay, F. L. Tomson, R. P. Kanteti, V. K. Viswanathan, and G. Hecht Balance of bacterial pro- and anti-inflammatory mediators dictates net effect of enteropathogenic Escherichia coli on intestinal epithelial cells Am J Physiol Gastrointest Liver Physiol, April 1, 2006; 290(4): G685 - G694. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Tseng, J. Do, J. H. Widdicombe, and T. E. Machen Innate immune responses of human tracheal epithelium to Pseudomonas aeruginosa flagellin, TNF-{alpha}, and IL-1beta Am J Physiol Cell Physiol, March 1, 2006; 290(3): C678 - C690. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C Mueller and A J Macpherson Layers of mutualism with commensal bacteria protect us from intestinal inflammation Gut, February 1, 2006; 55(2): 276 - 284. [Full Text] [PDF]
|
|
|
|
|
|
|
