Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 453K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hornef, M. W. Articles by Normark, S. Search for Related Content PubMed PubMed Citation Articles by Hornef, M. W. Articles by Normark, S. Social Bookmarking                      What's this?

¹ Microbiology and Tumor Biology Center and Swedish Institute for Infectious Disease Control, Karolinska Institutet, 17177 Stockholm, Sweden
² INSERM U478, Faculté de Médécine Xavier Bichat, 75870 Paris, France

Address correspondence to Mathias Hornef, Swedish Institute for Infectious Disease Control (SMI), 17182 Solna, Sweden. Phone: 46-8-457-2418; Fax: 46-8-302566; email: mathias.hornef{at}smi.ki.se

Toll-like receptor (TLR)4 has recently been shown to reside in the Golgi apparatus of intestinal crypt epithelial m-IC_cl2 cells, colocalizing with internalized lipopolysaccharide (LPS). Here we demonstrate that disruption of the integrity of the Golgi apparatus significantly reduced LPS-mediated nuclear factor B activation. Also, the TLR4 adaptor protein MyD88 and the serine/threonine kinase IRAK-1 were rapidly recruited to the Golgi apparatus upon stimulation. LPS-mediated activation required lipid raft formation and intact clathrin-dependent internalization. In contrast to macrophages, prevention of ligand internalization by use of LPS-coated beads significantly impaired recognition by epithelial cells. The localization of TLR4 to the Golgi apparatus was abrogated by expression of a genetically modified form of the TLR4 binding chaperone gp96. Thus, our data provide evidence that in contrast to the situation in macrophages, LPS recognition in intestinal epithelial cells may occur in the Golgi apparatus and require LPS internalization.

Key Words: endotoxin • Golgi apparatus • innate immunity • mucosal immunology

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Gribar, S. C., Sodhi, C. P., Richardson, W. M., Anand, R. J., Gittes, G. K., Branca, M. F., Jakub, A., Shi, X.-h., Shah, S., Ozolek, J. A., Hackam, D. J. (2009). Reciprocal Expression and Signaling of TLR4 and TLR9 in the Pathogenesis and Treatment of Necrotizing Enterocolitis. J. Immunol. 182: 636-646 [Abstract] [Full Text]  
• Chassin, C., Vimont, S., Cluzeaud, F., Bens, M., Goujon, J.-M., Fernandez, B., Hertig, A., Rondeau, E., Arlet, G., Hornef, M. W., Vandewalle, A. (2008). TLR4 Facilitates Translocation of Bacteria across Renal Collecting Duct Cells. J. Am. Soc. Nephrol. 19: 2364-2374 [Abstract] [Full Text]  
• Rodrigues, A., Queiroz, D. B.C., Honda, L., Silva, E. J. R., Hall, S. H., Avellar, M. C. W. (2008). Activation of Toll-Like Receptor 4 (TLR4) by In Vivo and In Vitro Exposure of Rat Epididymis to Lipopolysaccharide from Escherichia Coli. Biol. Reprod. 79: 1135-1147 [Abstract] [Full Text]  
• El-Achkar, T. M., Wu, X.-R., Rauchman, M., McCracken, R., Kiefer, S., Dagher, P. C. (2008). Tamm-Horsfall protein protects the kidney from ischemic injury by decreasing inflammation and altering TLR4 expression. Am. J. Physiol. Renal Physiol. 295: F534-F544 [Abstract] [Full Text]  
• Na, X., Kim, H., Moyer, M. P., Pothoulakis, C., LaMont, J. T. (2008). gp96 Is a Human Colonocyte Plasma Membrane Binding Protein for Clostridium difficile Toxin A. Infect. Immun. 76: 2862-2871 [Abstract] [Full Text]  
• Bhattacharyya, S., Gill, R., Chen, M. L., Zhang, F., Linhardt, R. J., Dudeja, P. K., Tobacman, J. K. (2008). Toll-like Receptor 4 Mediates Induction of the Bcl10-NF{kappa}B-Interleukin-8 Inflammatory Pathway by Carrageenan in Human Intestinal Epithelial Cells. J. Biol. Chem. 283: 10550-10558 [Abstract] [Full Text]  
• Davey, M., Liu, X., Ukai, T., Jain, V., Gudino, C., Gibson, F. C. III, Golenbock, D., Visintin, A., Genco, C. A. (2008). Bacterial Fimbriae Stimulate Proinflammatory Activation in the Endothelium through Distinct TLRs. J. Immunol. 180: 2187-2195 [Abstract] [Full Text]  
• Tissieres, P., Dunn-Siegrist, I., Schappi, M., Elson, G., Comte, R., Nobre, V., Pugin, J. (2008). Soluble MD-2 is an acute-phase protein and an opsonin for Gram-negative bacteria. Blood 111: 2122-2131 [Abstract] [Full Text]  
• Takahashi, K., Shibata, T., Akashi-Takamura, S., Kiyokawa, T., Wakabayashi, Y., Tanimura, N., Kobayashi, T., Matsumoto, F., Fukui, R., Kouro, T., Nagai, Y., Takatsu, K., Saitoh, S.-i., Miyake, K. (2007). A protein associated with Toll-like receptor (TLR) 4 (PRAT4A) is required for TLR-dependent immune responses. JEM 204: 2963-2976 [Abstract] [Full Text]  
• Shuang Chen, , Wong, M. H., Schulte, D. J., Arditi, M., Michelsen, K. S. (2007). Differential expression of Toll-like receptor 2 (TLR2) and responses to TLR2 ligands between human and murine vascular endothelial cells. Innate Immunity 13: 281-296 [Abstract]  
• Bhattacharyya, S., Borthakur, A., Pant, N., Dudeja, P. K., Tobacman, J. K. (2007). Bcl10 mediates LPS-induced activation of NF-{kappa}B and IL-8 in human intestinal epithelial cells. Am. J. Physiol. Gastrointest. Liver Physiol. 293: G429-G437 [Abstract] [Full Text]  
• Sterzenbach, T., Lee, S. K., Brenneke, B., von Goetz, F., Schauer, D. B., Fox, J. G., Suerbaum, S., Josenhans, C. (2007). Inhibitory Effect of Enterohepatic Helicobacter hepaticus on Innate Immune Responses of Mouse Intestinal Epithelial Cells. Infect. Immun. 75: 2717-2728 [Abstract] [Full Text]  
• Palazzo, M., Balsari, A., Rossini, A., Selleri, S., Calcaterra, C., Gariboldi, S., Zanobbio, L., Arnaboldi, F., Shirai, Y. F., Serrao, G., Rumio, C. (2007). Activation of Enteroendocrine Cells via TLRs Induces Hormone, Chemokine, and Defensin Secretion. J. Immunol. 178: 4296-4303 [Abstract] [Full Text]  
• Winkler, P., Ghadimi, D., Schrezenmeir, J., Kraehenbuhl, J.-P. (2007). Molecular and Cellular Basis of Microflora-Host Interactions. J. Nutr. 137: 756S-772S [Abstract] [Full Text]  
• Ashwood, P., Thompson, R. P. H., Powell, J. J. (2007). Fine Particles That Adsorb Lipopolysaccharide Via Bridging Calcium Cations May Mimic Bacterial Pathogenicity Towards Cells. Exp. Biol. Med. 232: 107-117 [Abstract] [Full Text]  
• Nakahira, K., Kim, H. P., Geng, X. H., Nakao, A., Wang, X., Murase, N., Drain, P. F., Wang, X., Sasidhar, M., Nabel, E. G., Takahashi, T., Lukacs, N. W., Ryter, S. W., Morita, K., Choi, A. M.K. (2006). Carbon monoxide differentially inhibits TLR signaling pathways by regulating ROS-induced trafficking of TLRs to lipid rafts. JEM 203: 2377-2389 [Abstract] [Full Text]  
• Warger, T., Hilf, N., Rechtsteiner, G., Haselmayer, P., Carrick, D. M., Jonuleit, H., von Landenberg, P., Rammensee, H.-G., Nicchitta, C. V., Radsak, M. P., Schild, H. (2006). Interaction of TLR2 and TLR4 Ligands with the N-terminal Domain of Gp96 Amplifies Innate and Adaptive Immune Responses. J. Biol. Chem. 281: 22545-22553 [Abstract] [Full Text]  
• Wakabayashi, Y., Kobayashi, M., Akashi-Takamura, S., Tanimura, N., Konno, K., Takahashi, K., Ishii, T., Mizutani, T., Iba, H., Kouro, T., Takaki, S., Takatsu, K., Oda, Y., Ishihama, Y., Saitoh, S.-i., Miyake, K. (2006). A Protein Associated with Toll-Like Receptor 4 (PRAT4A) Regulates Cell Surface Expression of TLR4. J. Immunol. 177: 1772-1779 [Abstract] [Full Text]  
• Gatti, G., Rivero, V., Motrich, R. D., Maccioni, M. (2006). Prostate epithelial cells can act as early sensors of infection by up-regulating TLR4 expression and proinflammatory mediators upon LPS stimulation. J. Leukoc. Biol. 79: 989-998 [Abstract] [Full Text]  
• Jou, I., Lee, J. H., Park, S. Y., Yoon, H. J., Joe, E.-H., Park, E. J. (2006). Gangliosides Trigger Inflammatory Responses via TLR4 in Brain Glia. Am. J. Pathol. 168: 1619-1630 [Abstract] [Full Text]  
• Lotz, M., Gutle, D., Walther, S., Menard, S., Bogdan, C., Hornef, M. W. (2006). Postnatal acquisition of endotoxin tolerance in intestinal epithelial cells. JEM 203: 973-984 [Abstract] [Full Text]  
• Yu, F.-S. X., Hazlett, L. D. (2006). Toll-like Receptors and the Eye.. IOVS 47: 1255-1263 [Full Text]  
• Cario, E., Golenbock, D. T., Visintin, A., Runzi, M., Gerken, G., Podolsky, D. K. (2006). Trypsin-Sensitive Modulation of Intestinal Epithelial MD-2 as Mechanism of Lipopolysaccharide Tolerance. J. Immunol. 176: 4258-4266 [Abstract] [Full Text]  
• Chabot, S., Wagner, J. S., Farrant, S., Neutra, M. R. (2006). TLRs Regulate the Gatekeeping Functions of the Intestinal Follicle-Associated Epithelium. J. Immunol. 176: 4275-4283 [Abstract] [Full Text]  
• Fritz, J. H., Girardin, S. E. (2005). How Toll-like receptors and Nod-like receptors contribute to innate immunity in mammals. Innate Immunity 11: 390-394 [Abstract]  
• Watson, C. J., Hoare, C. J., Garrod, D. R., Carlson, G. L., Warhurst, G. (2005). Interferon-{gamma} selectively increases epithelial permeability to large molecules by activating different populations of paracellular pores. J. Cell Sci. 118: 5221-5230 [Abstract] [Full Text]  
• Coats, S. R., Pham, T.-T. T., Bainbridge, B. W., Reife, R. A., Darveau, R. P. (2005). MD-2 Mediates the Ability of Tetra-Acylated and Penta-Acylated Lipopolysaccharides to Antagonize Escherichia coli Lipopolysaccharide at the TLR4 Signaling Complex. J. Immunol. 175: 4490-4498 [Abstract] [Full Text]  
• Andonegui, G., Kerfoot, S. M., McNagny, K., Ebbert, K. V. J., Patel, K. D., Kubes, P. (2005). Platelets express functional Toll-like receptor-4. Blood 106: 2417-2423 [Abstract] [Full Text]  
• Maung, A. A., Fujimi, S., Miller, M. L., MacConmara, M. P., Mannick, J. A., Lederer, J. A. (2005). Enhanced TLR4 reactivity following injury is mediated by increased p38 activation. J. Leukoc. Biol. 78: 565-573 [Abstract] [Full Text]  
• Cario, E (2005). BACTERIAL INTERACTIONS WITH CELLS OF THE INTESTINAL MUCOSA: TOLL-LIKE RECEPTORS AND NOD2. Gut 54: 1182-1193 [Full Text]  
• Fort, M. M., Mozaffarian, A., Stover, A. G., Correia, J. d. S., Johnson, D. A., Crane, R. T., Ulevitch, R. J., Persing, D. H., Bielefeldt-Ohmann, H., Probst, P., Jeffery, E., Fling, S. P., Hershberg, R. M. (2005). A Synthetic TLR4 Antagonist Has Anti-Inflammatory Effects in Two Murine Models of Inflammatory Bowel Disease. J. Immunol. 174: 6416-6423 [Abstract] [Full Text]  
• Mumy, K. L., McCormick, B. A. (2005). Events at the Host-Microbial Interface of the Gastrointestinal Tract II. Role of the intestinal epithelium in pathogen-induced inflammation. Am. J. Physiol. Gastrointest. Liver Physiol. 288: G854-G859 [Abstract] [Full Text]  
• Abreu, M. T., Fukata, M., Arditi, M. (2005). TLR Signaling in the Gut in Health and Disease. J. Immunol. 174: 4453-4460 [Abstract] [Full Text]  
• Morris, G. E., Whyte, M. K. B., Martin, G. F., Jose, P. J., Dower, S. K., Sabroe, I. (2005). Agonists of Toll-like Receptors 2 and 4 Activate Airway Smooth Muscle via Mononuclear Leukocytes. Am. J. Respir. Crit. Care Med. 171: 814-822 [Abstract] [Full Text]  
• Suzuki, T., Nakanishi, K., Tsutsui, H., Iwai, H., Akira, S., Inohara, N., Chamaillard, M., Nunez, G., Sasakawa, C. (2005). A Novel Caspase-1/Toll-like Receptor 4-independent Pathway of Cell Death Induced by Cytosolic Shigella in Infected Macrophages. J. Biol. Chem. 280: 14042-14050 [Abstract] [Full Text]  
• MacDonald, T. T., Monteleone, G. (2005). Immunity, Inflammation, and Allergy in the Gut. Science 307: 1920-1925 [Abstract] [Full Text]  
• West, A. P., Dancho, B. A., Mizel, S. B. (2005). Gangliosides Inhibit Flagellin Signaling in the Absence of an Effect on Flagellin Binding to Toll-like Receptor 5. J. Biol. Chem. 280: 9482-9488 [Abstract] [Full Text]  
• Tobias, P., Curtiss, L. K. (2005). Thematic review series: The Immune System and Atherogenesis. Paying the price for pathogen protection: toll receptors in atherogenesis. J. Lipid Res. 46: 404-411 [Abstract] [Full Text]  
• Bellocchio, S., Gaziano, R., Bozza, S., Rossi, G., Montagnoli, C., Perruccio, K., Calvitti, M., Pitzurra, L., Romani, L. (2005). Liposomal amphotericin B activates antifungal resistance with reduced toxicity by diverting Toll-like receptor signalling from TLR-2 to TLR-4. J Antimicrob Chemother 55: 214-222 [Abstract] [Full Text]  
• Hapfelmeier, S., Stecher, B., Barthel, M., Kremer, M., Muller, A. J., Heikenwalder, M., Stallmach, T., Hensel, M., Pfeffer, K., Akira, S., Hardt, W.-D. (2005). The Salmonella Pathogenicity Island (SPI)-2 and SPI-1 Type III Secretion Systems Allow Salmonella Serovar typhimurium to Trigger Colitis via MyD88-Dependent and MyD88-Independent Mechanisms. J. Immunol. 174: 1675-1685 [Abstract] [Full Text]  
• Bambou, J.-C., Giraud, A., Menard, S., Begue, B., Rakotobe, S., Heyman, M., Taddei, F., Cerf-Bensussan, N., Gaboriau-Routhiau, V. (2004). In Vitro and ex Vivo Activation of the TLR5 Signaling Pathway in Intestinal Epithelial Cells by a Commensal Escherichia coli Strain. J. Biol. Chem. 279: 42984-42992 [Abstract] [Full Text]  
• Abrahams, V. M., Bole-Aldo, P., Kim, Y. M., Straszewski-Chavez, S. L., Chaiworapongsa, T., Romero, R., Mor, G. (2004). Divergent Trophoblast Responses to Bacterial Products Mediated by TLRs. J. Immunol. 173: 4286-4296 [Abstract] [Full Text]  
• Bocharov, A. V., Baranova, I. N., Vishnyakova, T. G., Remaley, A. T., Csako, G., Thomas, F., Patterson, A. P., Eggerman, T. L. (2004). Targeting of Scavenger Receptor Class B Type I by Synthetic Amphipathic {alpha}-Helical-containing Peptides Blocks Lipopolysaccharide (LPS) Uptake and LPS-induced Pro-inflammatory Cytokine Responses in THP-1 Monocyte Cells. J. Biol. Chem. 279: 36072-36082 [Abstract] [Full Text]  
• Armstrong, L., Medford, A. R. L., Uppington, K. M., Robertson, J., Witherden, I. R., Tetley, T. D., Millar, A. B. (2004). Expression of Functional Toll-Like Receptor-2 and -4 on Alveolar Epithelial Cells. Am. J. Respir. Cell Mol. Bio. 31: 241-245 [Abstract] [Full Text]  
• Leifer, C. A., Kennedy, M. N., Mazzoni, A., Lee, C., Kruhlak, M. J., Segal, D. M. (2004). TLR9 Is Localized in the Endoplasmic Reticulum Prior to Stimulation. J. Immunol. 173: 1179-1183 [Abstract] [Full Text]  
• Mazzoni, A., Segal, D. M. (2004). Controlling the Toll road to dendritic cell polarization. J. Leukoc. Biol. 75: 721-730 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS