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*
Institute of Cancer Research and Molecular Biology, Norwegian University of Science and Technology, Trondheim, Norway;
Instituto di Microbiologia, Facolta di Medicina e Chirurgia, Universita degli Studi di Messina, Messina, Italy; and
Department of Medicine, Maxwell Finland Laboratory for Infectious Diseases, Boston Medical Center and Boston University School of Medicine, Boston, MA 02118
Human Toll like receptor (TLR) 2 has been implicated as a signaling
receptor for LPS from Gram-negative bacteria and cell wall components
from Gram-positive organisms. In this study, we investigated whether
TLR2 can signal cell activation by the heat-killed group B streptococci
type III (GBS) and Listeria monocytogenes (HKLM). HKLM,
but not GBS, showed a time- and dose-dependent activation of Chinese
hamster ovary cells transfected with human TLR2, as measured by
translocation of NF-
B and induction of IL-6 production. A mAb
recognizing a TLR2-associated epitope (TL2.1) was generated that
inhibited IL-6 production from Chinese hamster ovary-TLR2 cells
stimulated with HKLM or LPS. The TL2.1 mAb reduced HKLM-induced TNF
production from human monocytes by 60%, whereas a CD14 mAb (3C10)
reduced the TNF production by 30%. However, coadministrating TL2.1 and
3C10 inhibited the TNF response by 80%. In contrast to this,
anti-CD14 blocked LPS-induced TNF production from monocytes,
whereas anti-TLR2 showed no inhibition. Neither TL2.1 nor 3C10
affected GBS-induced TNF production. These results show that TLR2 can
function as a signaling receptor for HKLM, possibly together with CD14,
but that TLR2 is unlikely to be involved in cell activation by GBS.
Furthermore, although LPS can activate transfected cell lines through
TLR2, this receptor does not seem to be the main transducer of LPS
activation of human monocytes. Thus, our data demonstrate the ability
of TLR2 to distinguish between different
pathogens.
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P. Henneke, O. Takeuchi, R. Malley, E. Lien, R. R. Ingalls, M. W. Freeman, T. Mayadas, V. Nizet, S. Akira, D. L. Kasper, et al. Cellular Activation, Phagocytosis, and Bactericidal Activity Against Group B Streptococcus Involve Parallel Myeloid Differentiation Factor 88-Dependent and Independent Signaling Pathways J. Immunol., October 1, 2002; 169(7): 3970 - 3977. [Abstract] [Full Text] [PDF]
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T. H. Flo, L. Ryan, E. Latz, O. Takeuchi, B. G. Monks, E. Lien, O. Halaas, S. Akira, G. Skjak-Brak, D. T. Golenbock, et al. Involvement of Toll-like Receptor (TLR) 2 and TLR4 in Cell Activation by Mannuronic Acid Polymers J. Biol. Chem., September 13, 2002; 277(38): 35489 - 35495. [Abstract] [Full Text] [PDF]
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M. D. Lehner, F. Schwoebel, A. Kotlyarov, M. Leist, M. Gaestel, and T. Hartung Mitogen-Activated Protein Kinase-Activated Protein Kinase 2-Deficient Mice Show Increased Susceptibility to Listeria monocytogenes Infection J. Immunol., May 1, 2002; 168(9): 4667 - 4673. [Abstract] [Full Text] [PDF]
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H.-K. Lee, J. Lee, and P. S. Tobias Two Lipoproteins Extracted from Escherichia coli K-12 LCD25 Lipopolysaccharide Are the Major Components Responsible for Toll-Like Receptor 2-Mediated Signaling J. Immunol., April 15, 2002; 168(8): 4012 - 4017. [Abstract] [Full Text] [PDF]
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 R. Berner, B. Furll, F. Stelter, J. Drose, H.-P. Muller, and C. Schutt Elevated Levels of Lipopolysaccharide-Binding Protein and Soluble CD14 in Plasma in Neonatal Early-Onset Sepsis Clin. Vaccine Immunol., March 1, 2002; 9(2): 440 - 445. [Abstract] [Full Text] [PDF]
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T. Vasselon and P. A. Detmers Toll Receptors: a Central Element in Innate Immune Responses Infect. Immun., March 1, 2002; 70(3): 1033 - 1041. [Full Text] [PDF]
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R. Tamai, T. Sakuta, K. Matsushita, M. Torii, O. Takeuchi, S. Akira, S. Akashi, T. Espevik, S. Sugawara, and H. Takada Human Gingival CD14+ Fibroblasts Primed with Gamma Interferon Increase Production of Interleukin-8 in Response to Lipopolysaccharide through Up-Regulation of Membrane CD14 and MyD88 mRNA Expression Infect. Immun., March 1, 2002; 70(3): 1272 - 1278. [Abstract] [Full Text] [PDF]
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A. Fox-Marsh and L. C. Harrison Emerging evidence that molecules expressed by mammalian tissue grafts are recognized by the innate immune system J. Leukoc. Biol., March 1, 2002; 71(3): 401 - 409. [Abstract] [Full Text] [PDF]
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R. N. Fichorova, A. O. Cronin, E. Lien, D. J. Anderson, and R. R. Ingalls Response to Neisseria gonorrhoeae by Cervicovaginal Epithelial Cells Occurs in the Absence of Toll-Like Receptor 4-Mediated Signaling J. Immunol., March 1, 2002; 168(5): 2424 - 2432. [Abstract] [Full Text] [PDF]
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P. Massari, P. Henneke, Y. Ho, E. Latz, D. T. Golenbock, and L. M. Wetzler Cutting Edge: Immune Stimulation by Neisserial Porins Is Toll-Like Receptor 2 and MyD88 Dependent J. Immunol., February 15, 2002; 168(4): 1533 - 1537. [Abstract] [Full Text] [PDF]
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T. Wang, W. P. Lafuse, and B. S. Zwilling NF{kappa}B and Sp1 Elements Are Necessary for Maximal Transcription of Toll-like Receptor 2 Induced by Mycobacterium avium J. Immunol., December 15, 2001; 167(12): 6924 - 6932. [Abstract] [Full Text] [PDF]
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P. Henneke, O. Takeuchi, J. A. van Strijp, H.-K. Guttormsen, J. A. Smith, A. B. Schromm, T. A. Espevik, S. Akira, V. Nizet, D. L. Kasper, et al. Novel Engagement of CD14 and Multiple Toll-Like Receptors by Group B Streptococci J. Immunol., December 15, 2001; 167(12): 7069 - 7076. [Abstract] [Full Text] [PDF]
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H.-W. Mittrucker, M. Kursar, A. Kohler, R. Hurwitz, and S. H. E. Kaufmann Role of CD28 for the Generation and Expansion of Antigen-Specific CD8+ T Lymphocytes During Infection with Listeria monocytogenes J. Immunol., November 15, 2001; 167(10): 5620 - 5627. [Abstract] [Full Text] [PDF]
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S. Prebeck, C. Kirschning, S. Durr, C. da Costa, B. Donath, K. Brand, V. Redecke, H. Wagner, and T. Miethke Predominant Role of Toll-Like Receptor 2 Versus 4 in Chlamydia pneumoniae-Induced Activation of Dendritic Cells J. Immunol., September 15, 2001; 167(6): 3316 - 3323. [Abstract] [Full Text] [PDF]
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S. Sugawara, S. Yang, K. Iki, J. Hatakeyama, R. Tamai, O. Takeuchi, S. Akashi, T. Espevik, S. Akira, and H. Takada Monocytic Cell Activation by Nonendotoxic Glycoprotein from Prevotella intermedia ATCC 25611 Is Mediated by Toll-Like Receptor 2 Infect. Immun., August 1, 2001; 69(8): 4951 - 4957. [Abstract] [Full Text] [PDF]
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L. Rabehi, T. Irinopoulou, B. Cholley, N. Haeffner-Cavaillon, and M.-P. Carreno Gram-Positive and Gram-Negative Bacteria Do Not Trigger Monocytic Cytokine Production through Similar Intracellular Pathways Infect. Immun., July 1, 2001; 69(7): 4590 - 4599. [Abstract] [Full Text] [PDF]
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H.-H. Mu, A. D. Sawitzke, and B. C. Cole Presence of Lpsd Mutation Influences Cytokine Regulation In Vivo by the Mycoplasma arthritidis Mitogen Superantigen and Lethal Toxicity in Mice Infected with M. arthritidis Infect. Immun., June 1, 2001; 69(6): 3837 - 3844. [Abstract] [Full Text] [PDF]
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B. W. Jones, T. K. Means, K. A. Heldwein, M. A. Keen, P. J. Hill, J. T. Belisle, and M. J. Fenton Different Toll-like receptor agonists induce distinct macrophage responses J. Leukoc. Biol., June 1, 2001; 69(6): 1036 - 1044. [Abstract] [Full Text] [PDF]
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Y. Liu, Y. Wang, M. Yamakuchi, S. Isowaki, E. Nagata, Y. Kanmura, I. Kitajima, and I. Maruyama Upregulation of Toll-Like Receptor 2 Gene Expression in Macrophage Response to Peptidoglycan and High Concentration of Lipopolysaccharide Is Involved in NF-{kappa}B Activation Infect. Immun., May 1, 2001; 69(5): 2788 - 2796. [Abstract] [Full Text] [PDF]
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M. D. Lehner, S. Morath, K. S. Michelsen, R. R. Schumann, and T. Hartung Induction of Cross-Tolerance by Lipopolysaccharide and Highly Purified Lipoteichoic Acid Via Different Toll-Like Receptors Independent of Paracrine Mediators J. Immunol., April 15, 2001; 166(8): 5161 - 5167. [Abstract] [Full Text] [PDF]
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R. R. Ingalls, E. Lien, and D. T. Golenbock Membrane-Associated Proteins of a Lipopolysaccharide-Deficient Mutant of Neisseria meningitidis Activate the Inflammatory Response through Toll-Like Receptor 2 Infect. Immun., April 1, 2001; 69(4): 2230 - 2236. [Abstract] [Full Text] [PDF]
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J. E. Wang, A. Warris, E. A. Ellingsen, P. F. Jorgensen, T. H. Flo, T. Espevik, R. Solberg, P. E. Verweij, and A. O. Aasen Involvement of CD14 and Toll-Like Receptors in Activation of Human Monocytes by Aspergillus fumigatus Hyphae Infect. Immun., April 1, 2001; 69(4): 2402 - 2406. [Abstract] [Full Text] [PDF]
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T. Kielian, B. Barry, and W. F. Hickey CXC Chemokine Receptor-2 Ligands Are Required for Neutrophil-Mediated Host Defense in Experimental Brain Abscesses1 J. Immunol., April 1, 2001; 166(7): 4634 - 4643. [Abstract] [Full Text] [PDF]
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T. H. Flo, O. Halaas, S. Torp, L. Ryan, E. Lien, B. Dybdahl, A. Sundan, and T. Espevik Differential expression of Toll-like receptor 2 in human cells J. Leukoc. Biol., March 1, 2001; 69(3): 474 - 481. [Abstract] [Full Text]
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E. Seki, H. Tsutsui, H. Nakano, N. M. Tsuji, K. Hoshino, O. Adachi, K. Adachi, S. Futatsugi, K. Kuida, O. Takeuchi, et al. Lipopolysaccharide-Induced IL-18 Secretion from Murine Kupffer Cells Independently of Myeloid Differentiation Factor 88 That Is Critically Involved in Induction of Production of IL-12 and IL-1{{beta}} J. Immunol., February 15, 2001; 166(4): 2651 - 2657. [Abstract] [Full Text] [PDF]
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E. Faure, L. Thomas, H. Xu, A. E. Medvedev, O. Equils, and M. Arditi Bacterial Lipopolysaccharide and IFN-{{gamma}} Induce Toll-Like Receptor 2 and Toll-Like Receptor 4 Expression in Human Endothelial Cells: Role of NF-{{kappa}}B Activation J. Immunol., February 1, 2001; 166(3): 2018 - 2024. [Abstract] [Full Text] [PDF]
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A. M. Hajjar, D. S. O'Mahony, A. Ozinsky, D. M. Underhill, A. Aderem, S. J. Klebanoff, and C. B. Wilson Cutting Edge: Functional Interactions Between Toll-Like Receptor (TLR) 2 and TLR1 or TLR6 in Response to Phenol-Soluble Modulin J. Immunol., January 1, 2001; 166(1): 15 - 19. [Abstract] [Full Text] [PDF]
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T. H. Flo, L. Ryan, L. Kilaas, G. Skjak-Brak, R. R. Ingalls, A. Sundan, D. T. Golenbock, and T. Espevik Involvement of CD14 and beta 2-Integrins in Activating Cells with Soluble and Particulate Lipopolysaccharides and Mannuronic Acid Polymers Infect. Immun., December 1, 2000; 68(12): 6770 - 6776. [Abstract] [Full Text] [PDF]
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T. Wang, W. P. Lafuse, and B. S. Zwilling Regulation of Toll-Like Receptor 2 Expression by Macrophages Following Mycobacterium avium Infection J. Immunol., December 1, 2000; 165(11): 6308 - 6313. [Abstract] [Full Text] [PDF]
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A. Ozinsky, D. M. Underhill, J. D. Fontenot, A. M. Hajjar, K. D. Smith, C. B. Wilson, L. Schroeder, and A. Aderem The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between Toll-like receptors PNAS, November 22, 2000; (2000) 250476497. [Abstract] [Full Text]
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R. I. Tapping, S. Akashi, K. Miyake, P. J. Godowski, and P. S. Tobias Toll-Like Receptor 4, But Not Toll-Like Receptor 2, Is a Signaling Receptor for Escherichia and Salmonella Lipopolysaccharides J. Immunol., November 15, 2000; 165(10): 5780 - 5787. [Abstract] [Full Text] [PDF]
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E. Lorenz, J. P. Mira, K. L. Cornish, N. C. Arbour, and D. A. Schwartz A Novel Polymorphism in the Toll-Like Receptor 2 Gene and Its Potential Association with Staphylococcal Infection Infect. Immun., November 1, 2000; 68(11): 6398 - 6401. [Abstract] [Full Text] [PDF]
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R. R. Ingalls, E. Lien, and D. T. Golenbock Differential roles of TLR2 and TLR4 in the host response to Gram-negative bacteria: lessons from a lipopolysaccharide-deficient mutant of Neisseria meningitidis Innate Immunity, October 1, 2000; 6(5): 411 - 415. [Abstract] [PDF]
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S. Thoma-Uszynski, S. M. Kiertscher, M. T. Ochoa, D. A. Bouis, M. V. Norgard, K. Miyake, P. J. Godowski, M. D. Roth, and R. L. Modlin Activation of Toll-Like Receptor 2 on Human Dendritic Cells Triggers Induction of IL-12, But Not IL-10 J. Immunol., October 1, 2000; 165(7): 3804 - 3810. [Abstract] [Full Text] [PDF]
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M. Hirschfeld, Y. Ma, J. H. Weis, S. N. Vogel, and J. J. Weis Cutting Edge: Repurification of Lipopolysaccharide Eliminates Signaling Through Both Human and Murine Toll-Like Receptor 2 J. Immunol., July 15, 2000; 165(2): 618 - 622. [Abstract] [Full Text] [PDF]
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E. Lien, J. C. Chow, L. D. Hawkins, P. D. McGuinness, K. Miyake, T. Espevik, F. Gusovsky, and D. T. Golenbock A Novel Synthetic Acyclic Lipid A-like Agonist Activates Cells via the Lipopolysaccharide/Toll-like Receptor 4 Signaling Pathway J. Biol. Chem., January 12, 2001; 276(3): 1873 - 1880. [Abstract] [Full Text] [PDF]
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J. da Silva Correia, K. Soldau, U. Christen, P. S. Tobias, and R. J. Ulevitch Lipopolysaccharide Is in Close Proximity to Each of the Proteins in Its Membrane Receptor Complex. TRANSFER FROM CD14 TO TLR4 AND MD-2 J. Biol. Chem., June 8, 2001; 276(24): 21129 - 21135. [Abstract] [Full Text] [PDF]
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A. Ozinsky, D. M. Underhill, J. D. Fontenot, A. M. Hajjar, K. D. Smith, C. B. Wilson, L. Schroeder, and A. Aderem The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between Toll-like receptors PNAS, December 5, 2000; 97(25): 13766 - 13771. [Abstract] [Full Text] [PDF]
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S. Sasu, D. LaVerda, N. Qureshi, D. T. Golenbock, and D. Beasley Chlamydia pneumoniae and Chlamydial Heat Shock Protein 60 Stimulate Proliferation of Human Vascular Smooth Muscle Cells via Toll-Like Receptor 4 and p44/p42 Mitogen-Activated Protein Kinase Activation Circ. Res., August 3, 2001; 89(3): 244 - 250. [Abstract] [Full Text] [PDF]
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