International Immunology, Vol. 12, No. 1, 113-117,
January 2000
© 2000 Japanese Society for Immunology
Cellular responses to bacterial cell wall components are mediated through MyD88-dependent signaling cascades
1 Department of Host Defense, Research Institute for Microbial Diseases, Osaka University and
2 CREST of Japan Science and Technology Corp., 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan
3 Department of Oral Microbiology, Asahi University School of Dentistry, 1851-1 Hozumi, Hozumi-Cho, Motosu-Gun, Gifu 501-0296, Japan
Correspondence to: S. Akira
MyD88 is an adaptor molecule essential for signaling via the Toll-like receptor (TLR)/IL-1 receptor family. TLR4 is a member of the TLR family and a point mutation in the Tlr4 gene causes hyporesponsiveness to lipopolysaccharide (LPS) in C3H/HeJ mice. We have previously shown that both TLR4- and MyD88-deficient mice are hyporesponsive to LPS. In this study we examined the responsiveness of these two knockout mice to various bacterial cell wall components. Cells from TLR4-deficient mice responded to several kinds of LPS, peptidoglycan and crude cell wall preparation from Gram-positive bacteria and mycobacterial lysates. In contrast, macrophages and splenocytes from MyD88-deficient mice did not respond to any of the bacterial components we tested. These results show that MyD88 is essential for the cellular response to bacterial cell wall components.
Keywords: Gram-positive bacteria, innate immunity, lipopolysaccharide, macrophage, Toll-like receptor
Transmitting editor: K. Sugamura
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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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C. Alexander and E. Th. Rietschel Invited review: Bacterial lipopolysaccharides and innate immunity Innate Immunity, June 1, 2001; 7(3): 167 - 202. [Abstract] [PDF]
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T. Kaisho, O. Takeuchi, T. Kawai, K. Hoshino, and S. Akira Endotoxin-Induced Maturation of MyD88-Deficient Dendritic Cells J. Immunol., May 1, 2001; 166(9): 5688 - 5694. [Abstract] [Full Text] [PDF]
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S. Yang, R. Tamai, S. Akashi, O. Takeuchi, S. Akira, S. Sugawara, and H. Takada Synergistic Effect of Muramyldipeptide with Lipopolysaccharide or Lipoteichoic Acid To Induce Inflammatory Cytokines in Human Monocytic Cells in Culture Infect. Immun., April 1, 2001; 69(4): 2045 - 2053. [Abstract] [Full Text] [PDF]
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Q. Wang, R. Dziarski, C. J. Kirschning, M. Muzio, and D. Gupta Micrococci and Peptidoglycan Activate TLR2{right-arrow}MyD88{right-arrow}IRAK{right-arrow}TRAF{right-arrow}NIK{right-arrow}IKK{right-arrow}NF-{kappa}B Signal Transduction Pathway That Induces Transcription of Interleukin-8 Infect. Immun., April 1, 2001; 69(4): 2270 - 2276. [Abstract] [Full Text] [PDF]
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T. K. Means, B. W. Jones, A. B. Schromm, B. A. Shurtleff, J. A. Smith, J. Keane, D. T. Golenbock, S. N. Vogel, and M. J. Fenton Differential Effects of a Toll-Like Receptor Antagonist on Mycobacterium tuberculosis-Induced Macrophage Responses J. Immunol., March 15, 2001; 166(6): 4074 - 4082. [Abstract] [Full Text] [PDF]
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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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R. Dziarski, Q. Wang, K. Miyake, C. J. Kirschning, and D. Gupta MD-2 Enables Toll-Like Receptor 2 (TLR2)-Mediated Responses to Lipopolysaccharide and Enhances TLR2-Mediated Responses to Gram-Positive and Gram-Negative Bacteria and Their Cell Wall Components J. Immunol., February 1, 2001; 166(3): 1938 - 1944. [Abstract] [Full Text] [PDF]
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S. Sato, F. Nomura, T. Kawai, O. Takeuchi, P. F. Muhlradt, K. Takeda, and S. Akira Synergy and Cross-Tolerance Between Toll-Like Receptor (TLR) 2- and TLR4-Mediated Signaling Pathways J. Immunol., December 15, 2000; 165(12): 7096 - 7101. [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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O. Takeuchi, K. Hoshino, and S. Akira Cutting Edge: TLR2-Deficient and MyD88-Deficient Mice Are Highly Susceptible to Staphylococcus aureus Infection J. Immunol., November 15, 2000; 165(10): 5392 - 5396. [Abstract] [Full Text] [PDF]
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S. Akira, K. Hoshino, and T. Kaisho The role of Toll-like receptors and MyD88 in innate immune responses Innate Immunity, October 1, 2000; 6(5): 383 - 387. [Abstract] [PDF]
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N. W. J. Schroder, B. Opitz, N. Lamping, K. S. Michelsen, U. Zahringer, U. B. Gobel, and R. R. Schumann Involvement of Lipopolysaccharide Binding Protein, CD14, and Toll-Like Receptors in the Initiation of Innate Immune Responses by Treponema Glycolipids J. Immunol., September 1, 2000; 165(5): 2683 - 2693. [Abstract] [Full Text] [PDF]
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R. M. Vabulas, P. Ahmad-Nejad, C. da Costa, T. Miethke, C. J. Kirschning, H. Hacker, and H. Wagner Endocytosed HSP60s Use Toll-like Receptor 2 (TLR2) and TLR4 to Activate the Toll/Interleukin-1 Receptor Signaling Pathway in Innate Immune Cells J. Biol. Chem., August 10, 2001; 276(33): 31332 - 31339. [Abstract] [Full Text] [PDF]
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S. Maeda, M. Akanuma, Y. Mitsuno, Y. Hirata, K. Ogura, H. Yoshida, Y. Shiratori, and M. Omata Distinct Mechanism of Helicobacter pylori-mediated NF-kappa B Activation between Gastric Cancer Cells and Monocytic Cells J. Biol. Chem., November 21, 2001; 276(48): 44856 - 44864. [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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