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,¶
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* Department of Immunology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka, Japan;
Department of Molecular Immunology, Nara Institute Science and Technology, Ikoma, Nara, Japan;
Department of Virology, Osaka City University Medical School, Osaka,
Department of Cell Biology, Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga, Japan; and
¶ Core Research for Evolutional Science and Technology, Japan Science and Technology, Tokyo, Japan
Toll-like receptor (TLR)3 recognizes dsRNA and transduces signals to activate NF-
B and IFN-
promoter. Type I IFNs (IFN-
/) function as key cytokines in anti-viral host defense. Human fibroblasts express TLR3 on the cell surface, and anti-TLR3 mAb inhibits dsRNA-induced IFN- secretion by fibroblasts, suggesting that TLR3 acts on the cell surface to sense viral infection. In this study, we examined the expression and localization of human TLR3 in various DC subsets using anti-TLR3 mAb. In monocyte-derived immature dendritic cells (iDCs), TLR3 predominantly resided inside the cells but not on the cell surface. iDCs produced IL-12p70 and IFN- and - in response to poly(I:C). Similar response was observed in iDCs treated with rotavirus-derived dsRNA. These responses could not be blocked by pretreatment of the cells with anti-TLR3 mAb. In CD11c+ blood DCs, cytoplasmic retention of TLR3 was also observed as in monocyte-derived iDCs, again endorsing a different TLR3 distribution profile from fibroblasts. In precursor DC2, however, TLR3 could not be detected inside or outside the cells. Of note, there was a putative centrosomal protein that shared an epitope with TLR3 in myeloid DCs and precursor DC2, but not peripheral blood monocytes. Immunoelectron microscopic analysis revealed that TLR3, when stably expressed in the murine B cell line Ba/F3, was specifically accumulated in multivesicular bodies, a subcellular compartment situated in endocytic trafficking pathways. Thus, regulation and localization of TLR3 are different in each cell type, which may reflect participation of cell type-specific multiple pathways in antiviral IFN induction via TLR3.
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J. Sun, K. E. Duffy, C. T. Ranjith-Kumar, J. Xiong, R. J. Lamb, J. Santos, H. Masarapu, M. Cunningham, A. Holzenburg, R. T. Sarisky, et al. Structural and Functional Analyses of the Human Toll-like Receptor 3: ROLE OF GLYCOSYLATION J. Biol. Chem., April 21, 2006; 281(16): 11144 - 11151. [Abstract] [Full Text] [PDF]
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B. L. Fredericksen and M. Gale Jr. West Nile Virus Evades Activation of Interferon Regulatory Factor 3 through RIG-I-Dependent and -Independent Pathways without Antagonizing Host Defense Signaling J. Virol., March 15, 2006; 80(6): 2913 - 2923. [Abstract] [Full Text] [PDF]
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 T. Seya, T. Akazawa, T. Tsujita, and M. Matsumoto Role of Toll-like Receptors in Adjuvant-Augmented Immune Therapies. Evid. Based Complement. Altern. Med., March 1, 2006; 3(1): 31 - 38. [Abstract] [Full Text] [PDF]
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 C. M. Galdeano and G. Perdigon The Probiotic Bacterium Lactobacillus casei Induces Activation of the Gut Mucosal Immune System through Innate Immunity Clin. Vaccine Immunol., February 1, 2006; 13(2): 219 - 226. [Abstract] [Full Text] [PDF]
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M. Sasai, M. Matsumoto, and T. Seya The Kinase Complex Responsible for IRF-3-Mediated IFN-{beta} Production in Myeloid Dendritic Cells (mDC) J. Biochem., February 1, 2006; 139(2): 171 - 175. [Abstract] [Full Text] [PDF]
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 M. Wornle, H. Schmid, B. Banas, M. Merkle, A. Henger, M. Roeder, S. Blattner, E. Bock, M. Kretzler, H.-J. Grone, et al. Novel Role of Toll-Like Receptor 3 in Hepatitis C-Associated Glomerulonephritis Am. J. Pathol., February 1, 2006; 168(2): 370 - 385. [Abstract] [Full Text] [PDF]
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D. Wesch, S. Beetz, H.-H. Oberg, M. Marget, K. Krengel, and D. Kabelitz Direct Costimulatory Effect of TLR3 Ligand Poly(I:C) on Human {gamma}{delta} T Lymphocytes J. Immunol., February 1, 2006; 176(3): 1348 - 1354. [Abstract] [Full Text] [PDF]
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D. J. Groskreutz, M. M. Monick, L. S. Powers, T. O. Yarovinsky, D. C. Look, and G. W. Hunninghake Respiratory Syncytial Virus Induces TLR3 Protein and Protein Kinase R, Leading to Increased Double-Stranded RNA Responsiveness in Airway Epithelial Cells J. Immunol., February 1, 2006; 176(3): 1733 - 1740. [Abstract] [Full Text] [PDF]
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B. D. Rudd, J. J. Smit, R. A. Flavell, L. Alexopoulou, M. A. Schaller, A. Gruber, A. A. Berlin, and N. W. Lukacs Deletion of TLR3 Alters the Pulmonary Immune Environment and Mucus Production during Respiratory Syncytial Virus Infection J. Immunol., February 1, 2006; 176(3): 1937 - 1942. [Abstract] [Full Text] [PDF]
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N. K. Crellin, R. V. Garcia, O. Hadisfar, S. E. Allan, T. S. Steiner, and M. K. Levings Human CD4+ T Cells Express TLR5 and Its Ligand Flagellin Enhances the Suppressive Capacity and Expression of FOXP3 in CD4+CD25+ T Regulatory Cells J. Immunol., December 15, 2005; 175(12): 8051 - 8059. [Abstract] [Full Text] [PDF]
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M. Yasutomi, Y. Ohshima, N. Omata, A. Yamada, H. Iwasaki, Y. Urasaki, and M. Mayumi Erythromycin Differentially Inhibits Lipopolysaccharide- or Poly(I:C)-Induced but Not Peptidoglycan-Induced Activation of Human Monocyte-Derived Dendritic Cells J. Immunol., December 15, 2005; 175(12): 8069 - 8076. [Abstract] [Full Text] [PDF]
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T. Seya, K. Funami, M. Taniguchi, and M. Matsumoto Antibodies against human Toll-like receptors (TLRs): TLR distribution and localization in human dendritic cells Innate Immunity, December 1, 2005; 11(6): 369 - 374. [Abstract] [PDF]
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C. F. Narvaez, J. Angel, and M. A. Franco Interaction of Rotavirus with Human Myeloid Dendritic Cells J. Virol., December 1, 2005; 79(23): 14526 - 14535. [Abstract] [Full Text] [PDF]
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O. de Bouteiller, E. Merck, U. A. Hasan, S. Hubac, B. Benguigui, G. Trinchieri, E. E. M. Bates, and C. Caux Recognition of Double-stranded RNA by Human Toll-like Receptor 3 and Downstream Receptor Signaling Requires Multimerization and an Acidic pH J. Biol. Chem., November 18, 2005; 280(46): 38133 - 38145. [Abstract] [Full Text] [PDF]
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T. Nishiya, E. Kajita, S. Miwa, and A. L. DeFranco TLR3 and TLR7 Are Targeted to the Same Intracellular Compartments by Distinct Regulatory Elements J. Biol. Chem., November 4, 2005; 280(44): 37107 - 37117. [Abstract] [Full Text] [PDF]
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W. A. Derbigny, M. S. Kerr, and R. M. Johnson Pattern Recognition Molecules Activated by Chlamydia muridarum Infection of Cloned Murine Oviduct Epithelial Cell Lines J. Immunol., November 1, 2005; 175(9): 6065 - 6075. [Abstract] [Full Text] [PDF]
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C. Prehaud, F. Megret, M. Lafage, and M. Lafon Virus Infection Switches TLR-3-Positive Human Neurons To Become Strong Producers of Beta Interferon J. Virol., October 15, 2005; 79(20): 12893 - 12904. [Abstract] [Full Text] [PDF]
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S. K. Sanghavi and T. A. Reinhart Increased Expression of TLR3 in Lymph Nodes during Simian Immunodeficiency Virus Infection: Implications for Inflammation and Immunodeficiency J. Immunol., October 15, 2005; 175(8): 5314 - 5323. [Abstract] [Full Text] [PDF]
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C. S. Jack, N. Arbour, J. Manusow, V. Montgrain, M. Blain, E. McCrea, A. Shapiro, and J. P. Antel TLR Signaling Tailors Innate Immune Responses in Human Microglia and Astrocytes J. Immunol., October 1, 2005; 175(7): 4320 - 4330. [Abstract] [Full Text] [PDF]
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J. K. Bell, I. Botos, P. R. Hall, J. Askins, J. Shiloach, D. M. Segal, and D. R. Davies The molecular structure of the Toll-like receptor 3 ligand-binding domain PNAS, August 2, 2005; 102(31): 10976 - 10980. [Abstract] [Full Text] [PDF]
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 K. Pal, C. S. Kaetzel, K. Brundage, C. A. Cunningham, and C. F. Cuff Regulation of polymeric immunoglobulin receptor expression by reovirus J. Gen. Virol., August 1, 2005; 86(8): 2347 - 2357. [Abstract] [Full Text] [PDF]
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Z. Orinska, E. Bulanova, V. Budagian, M. Metz, M. Maurer, and S. Bulfone-Paus TLR3-induced activation of mast cells modulates CD8+ T-cell recruitment Blood, August 1, 2005; 106(3): 978 - 987. [Abstract] [Full Text] [PDF]
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J. Choe, M. S. Kelker, and I. A. Wilson Crystal Structure of Human Toll-Like Receptor 3 (TLR3) Ectodomain Science, July 22, 2005; 309(5734): 581 - 585. [Abstract] [Full Text] [PDF]
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L. C. Parker, M. K. B. Whyte, S. K. Dower, and I. Sabroe The expression and roles of Toll-like receptors in the biology of the human neutrophil J. Leukoc. Biol., June 1, 2005; 77(6): 886 - 892. [Abstract] [Full Text] [PDF]
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K. Yasuda, P. Yu, C. J. Kirschning, B. Schlatter, F. Schmitz, A. Heit, S. Bauer, H. Hochrein, and H. Wagner Endosomal Translocation of Vertebrate DNA Activates Dendritic Cells via TLR9-Dependent and -Independent Pathways J. Immunol., May 15, 2005; 174(10): 6129 - 6136. [Abstract] [Full Text] [PDF]
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M. Vijay-Kumar, J. R. Gentsch, W. J. Kaiser, N. Borregaard, M. K. Offermann, A. S. Neish, and A. T. Gewirtz Protein Kinase R Mediates Intestinal Epithelial Gene Remodeling in Response to Double-Stranded RNA and Live Rotavirus J. Immunol., May 15, 2005; 174(10): 6322 - 6331. [Abstract] [Full Text] [PDF]
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K. Li, Z. Chen, N. Kato, M. Gale Jr., and S. M. Lemon Distinct Poly(I-C) and Virus-activated Signaling Pathways Leading to Interferon-{beta} Production in Hepatocytes J. Biol. Chem., April 29, 2005; 280(17): 16739 - 16747. [Abstract] [Full Text] [PDF]
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J. Tissari, J. Siren, S. Meri, I. Julkunen, and S. Matikainen IFN-{alpha} Enhances TLR3-Mediated Antiviral Cytokine Expression in Human Endothelial and Epithelial Cells by Up-Regulating TLR3 Expression J. Immunol., April 1, 2005; 174(7): 4289 - 4294. [Abstract] [Full Text] [PDF]
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B. D. Rudd, E. Burstein, C. S. Duckett, X. Li, and N. W. Lukacs Differential Role for TLR3 in Respiratory Syncytial Virus-Induced Chemokine Expression J. Virol., March 15, 2005; 79(6): 3350 - 3357. [Abstract] [Full Text] [PDF]
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P. Decker, H. Singh-Jasuja, S. Haager, I. Kotter, and H.-G. Rammensee Nucleosome, the Main Autoantigen in Systemic Lupus Erythematosus, Induces Direct Dendritic Cell Activation via a MyD88-Independent Pathway: Consequences on Inflammation J. Immunol., March 15, 2005; 174(6): 3326 - 3334. [Abstract] [Full Text] [PDF]
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L. Guillot, R. Le Goffic, S. Bloch, N. Escriou, S. Akira, M. Chignard, and M. Si-Tahar 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., February 18, 2005; 280(7): 5571 - 5580. [Abstract] [Full Text] [PDF]
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