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* Department of Internal Medicine, Division of Clinical Pharmacology, University of Munich, Munich, Germany; and
Institute of Immunology, University of Heidelberg, Heidelberg, Germany
The Toll-like receptor (TLR)9 is critical for the recognition of immunostimulatory CpG motifs but may cooperate with other TLRs. We analyzed TLR1–10 mRNA expression by using quantitative real-time PCR in highly purified subsets of human PBMC and determined the sensitivity of these subsets to CpG oligodeoxynucleotides (ODN). TLR1 and TLR6 were expressed in all cell types examined. TLR10 was highly expressed in B cells and weakly expressed in plasmacytoid dendritic cells (PDC). High expression of TLR2 was characteristic for monocytes. PDC and B cells expressed marked levels of TLR7 and TLR9 and were directly sensitive to CpG ODN. In CpG ODN-stimulated PDC and B cells, TLR9 expression rapidly decreased, as opposed to TLR7, which was up-regulated in PDC and decreased in B cells. In monocytes, NK cells, and T cells, TLR7 was absent. Despite low expression of TLR9, monocytes, NK cells, and T cells did not respond to CpG ODN in the absence of PDC but were activated in the presence of PDC. In conclusion, our studies provide evidence that PDC and B cells, but not monocytes, NK cells, or T cells, are primary targets of CpG ODN in peripheral blood. The characteristic expression pattern of TLR1–10 in cellular subsets of human PBMC is consistent with the concept that TLR9 is essential in the recognition of CpG ODN in PDC and B cells. In addition, selective regulation of TLR7 expression in PDC and B cells by CpG ODN revealed TLR7 as a candidate TLR potentially involved in modulating the recognition of CpG motifs.
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B. Berghofer, G. Haley, T. Frommer, G. Bein, and H. Hackstein Natural and Synthetic TLR7 Ligands Inhibit CpG-A- and CpG-C-Oligodeoxynucleotide-Induced IFN-{alpha} Production J. Immunol., April 1, 2007; 178(7): 4072 - 4079. [Abstract] [Full Text] [PDF]
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C. Bourquin, L. Schmidt, V. Hornung, C. Wurzenberger, D. Anz, N. Sandholzer, S. Schreiber, A. Voelkl, G. Hartmann, and S. Endres Immunostimulatory RNA oligonucleotides trigger an antigen-specific cytotoxic T-cell and IgG2a response Blood, April 1, 2007; 109(7): 2953 - 2960. [Abstract] [Full Text] [PDF]
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A. R. M. Kraft, F. Krux, S. Schimmer, C. Ohlen, P. D. Greenberg, and U. Dittmer CpG oligodeoxynucleotides allow for effective adoptive T-cell therapy in chronic retroviral infection Blood, April 1, 2007; 109(7): 2982 - 2984. [Abstract] [Full Text] [PDF]
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J. P. Wang, D. R. Asher, M. Chan, E. A. Kurt-Jones, and R. W. Finberg Cutting Edge: Antibody-Mediated TLR7-Dependent Recognition of Viral RNA J. Immunol., March 15, 2007; 178(6): 3363 - 3367. [Abstract] [Full Text] [PDF]
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S. Hamm, A. Heit, M. Koffler, K. M. Huster, S. Akira, D. H. Busch, H. Wagner, and S. Bauer Immunostimulatory RNA is a potent inducer of antigen-specific cytotoxic and humoral immune response in vivo Int. Immunol., March 1, 2007; 19(3): 297 - 304. [Abstract] [Full Text] [PDF]
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J. Sawaki, H. Tsutsui, N. Hayashi, K. Yasuda, S. Akira, T. Tanizawa, and K. Nakanishi Type 1 cytokine/chemokine production by mouse NK cells following activation of their TLR/MyD88-mediated pathways Int. Immunol., March 1, 2007; 19(3): 311 - 320. [Abstract] [Full Text] [PDF]
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I. Bekeredjian-Ding, S. Inamura, T. Giese, H. Moll, S. Endres, A. Sing, U. Zahringer, and G. Hartmann Staphylococcus aureus Protein A Triggers T Cell-Independent B Cell Proliferation by Sensitizing B Cells for TLR2 Ligands J. Immunol., March 1, 2007; 178(5): 2803 - 2812. [Abstract] [Full Text] [PDF]
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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]
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 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]
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 A. Osterloh, U. Kalinke, S. Weiss, B. Fleischer, and M. Breloer Synergistic and Differential Modulation of Immune Responses by Hsp60 and Lipopolysaccharide J. Biol. Chem., February 16, 2007; 282(7): 4669 - 4680. [Abstract] [Full Text] [PDF]
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A. M.G. van der Aar, R. M. R. Sylva-Steenland, J. D. Bos, M. L. Kapsenberg, E. C. de Jong, and M. B. M. Teunissen Cutting Edge: Loss of TLR2, TLR4, and TLR5 on Langerhans Cells Abolishes Bacterial Recognition J. Immunol., February 15, 2007; 178(4): 1986 - 1990. [Abstract] [Full Text] [PDF]
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R. Zhou, H. Wei, and Z. Tian NK3-Like NK Cells Are Involved in Protective Effect of Polyinosinic-Polycytidylic Acid on Type 1 Diabetes in Nonobese Diabetic Mice J. Immunol., February 15, 2007; 178(4): 2141 - 2147. [Abstract] [Full Text] [PDF]
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J. Huggins, T. Pellegrin, R. E. Felgar, C. Wei, M. Brown, B. Zheng, E. C. B. Milner, S. H. Bernstein, I. Sanz, and M. S. Zand CpG DNA activation and plasma-cell differentiation of CD27- naive human B cells Blood, February 15, 2007; 109(4): 1611 - 1619. [Abstract] [Full Text] [PDF]
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D. Zipris, E. Lien, A. Nair, J. X. Xie, D. L. Greiner, J. P. Mordes, and A. A. Rossini TLR9-Signaling Pathways Are Involved in Kilham Rat Virus-Induced Autoimmune Diabetes in the Biobreeding Diabetes-Resistant Rat J. Immunol., January 15, 2007; 178(2): 693 - 701. [Abstract] [Full Text] [PDF]
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 M. Pashenkov, G. Goess, C. Wagner, M. Hormann, T. Jandl, A. Moser, C. M. Britten, J. Smolle, S. Koller, C. Mauch, et al. Phase II Trial of a Toll-Like Receptor 9-Activating Oligonucleotide in Patients With Metastatic Melanoma J. Clin. Oncol., December 20, 2006; 24(36): 5716 - 5724. [Abstract] [Full Text] [PDF]
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P. J. Popovic, R. DeMarco, M. T. Lotze, S. E. Winikoff, D. L. Bartlett, A. M. Krieg, Z. S. Guo, C. K. Brown, K. J. Tracey, and H. J. Zeh III High Mobility Group B1 Protein Suppresses the Human Plasmacytoid Dendritic Cell Response to TLR9 Agonists J. Immunol., December 15, 2006; 177(12): 8701 - 8707. [Abstract] [Full Text] [PDF]
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J. Tabiasco, E. Devevre, N. Rufer, B. Salaun, J.-C. Cerottini, D. Speiser, and P. Romero Human Effector CD8+ T Lymphocytes Express TLR3 as a Functional Coreceptor J. Immunol., December 15, 2006; 177(12): 8708 - 8713. [Abstract] [Full Text] [PDF]
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H. Bartz, N. M. Avalos, A. Baetz, K. Heeg, and A. H. Dalpke Involvement of suppressors of cytokine signaling in toll-like receptor-mediated block of dendritic cell differentiation Blood, December 15, 2006; 108(13): 4102 - 4108. [Abstract] [Full Text] [PDF]
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J. Wang, Y. Shao, T. A. Bennett, R. A. Shankar, P. D. Wightman, and L. G. Reddy The Functional Effects of Physical Interactions among Toll-like Receptors 7, 8, and 9 J. Biol. Chem., December 8, 2006; 281(49): 37427 - 37434. [Abstract] [Full Text] [PDF]
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K. A. Shirey, J.-Y. Jung, and J. M. Carlin Up-Regulation of Gamma Interferon Receptor Expression Due to Chlamydia-Toll-Like Receptor Interaction Does Not Enhance Signal Transducer and Activator of Transcription 1 Signaling Infect. Immun., December 1, 2006; 74(12): 6877 - 6884. [Abstract] [Full Text] [PDF]
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V. Hoene, M. Peiser, and R. Wanner Human monocyte-derived dendritic cells express TLR9 and react directly to the CpG-A oligonucleotide D19 J. Leukoc. Biol., December 1, 2006; 80(6): 1328 - 1336. [Abstract] [Full Text] [PDF]
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P. Paladino, D. T. Cummings, R. S. Noyce, and K. L. Mossman The IFN-Independent Response to Virus Particle Entry Provides a First Line of Antiviral Defense That Is Independent of TLRs and Retinoic Acid-Inducible Gene I J. Immunol., December 1, 2006; 177(11): 8008 - 8016. [Abstract] [Full Text] [PDF]
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K. K. B. Gorden, X. Qiu, J. J. L. Battiste, P. P. D. Wightman, J. P. Vasilakos, and S. S. Alkan Oligodeoxynucleotides Differentially Modulate Activation of TLR7 and TLR8 by Imidazoquinolines J. Immunol., December 1, 2006; 177(11): 8164 - 8170. [Abstract] [Full Text] [PDF]
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A. Dolganiuc, S. Chang, K. Kodys, P. Mandrekar, G. Bakis, M. Cormier, and G. Szabo Hepatitis C Virus (HCV) Core Protein-Induced, Monocyte-Mediated Mechanisms of Reduced IFN-{alpha} and Plasmacytoid Dendritic Cell Loss in Chronic HCV Infection J. Immunol., November 15, 2006; 177(10): 6758 - 6768. [Abstract] [Full Text] [PDF]
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P. S. Patole, R. D. Pawar, M. Lech, D. Zecher, H. Schmidt, S. Segerer, A. Ellwart, A. Henger, M. Kretzler, and H.-J. Anders Expression and regulation of Toll-like receptors in lupus-like immune complex glomerulonephritis of MRL-Fas(lpr) mice Nephrol. Dial. Transplant., November 1, 2006; 21(11): 3062 - 3073. [Abstract] [Full Text] [PDF]
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E. Hartmann, H. Graefe, A. Hopert, R. Pries, S. Rothenfusser, H. Poeck, B. Mack, S. Endres, G. Hartmann, and B. Wollenberg Analysis of Plasmacytoid and Myeloid Dendritic Cells in Nasal Epithelium Clin. Vaccine Immunol., November 1, 2006; 13(11): 1278 - 1286. [Abstract] [Full Text] [PDF]
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