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CUTTING EDGE |








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Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan;
Core Research for Evolutional Science and Technology of Japan Science and Technology Corporation, Osaka, Japan;
Institute of Immunology, Philipps University, Marburg, Germany; and
Immunobiology Research Group, Gesellschaft für Biotechnologische Forschung, Braunschweig, Germany
Mycoplasmas and their membranes are potent activators of macrophages, the active principle being lipoproteins and lipopeptides. Two stereoisomers of the mycoplasmal lipopeptide macrophage-activating lipopeptide-2 (MALP-2) differing in the configuration of the lipid moiety were synthesized and compared in their macrophage-activating potential, the R-MALP being >100 times more active than the S-MALP in stimulating the release of cytokines, chemokines, and NO. To assess the role of the Toll-like receptor (TLR) family in mycoplasmal lipopeptide signaling, the MALP-2-mediated responses were analyzed using macrophages from wild-type, TLR2-, TLR4-, and MyD88-deficient mice. TLR2- and MyD88-deficient cells showed severely impaired cytokine productions in response to R- and S-MALP. The MALP-induced activation of intracellular signaling molecules was fully dependent on both TLR2 and MyD88. There was a strong preference for the R-MALP in the recognition by its functional receptor, TLR2.
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E. S. Van Amersfoort, T. J. C. Van Berkel, and J. Kuiper Receptors, Mediators, and Mechanisms Involved in Bacterial Sepsis and Septic Shock Clin. Microbiol. Rev., July 1, 2003; 16(3): 379 - 414. [Abstract] [Full Text] [PDF] |
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G. Fenhalls, G. R. Squires, L. Stevens-Muller, J. Bezuidenhout, G. Amphlett, K. Duncan, and P. T. Lukey Associations between Toll-Like Receptors and Interleukin-4 in the Lungs of Patients with Tuberculosis Am. J. Respir. Cell Mol. Biol., July 1, 2003; 29(1): 28 - 38. [Abstract] [Full Text] [PDF] |
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M. Muroi, T. Ohnishi, S. Azumi-Mayuzumi, and K.-i. Tanamoto Lipopolysaccharide-Mimetic Activities of a Toll-Like Receptor 2-Stimulatory Substance(s) in Enterobacterial Lipopolysaccharide Preparations Infect. Immun., June 1, 2003; 71(6): 3221 - 3226. [Abstract] [Full Text] [PDF] |
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Z. Jiang, M. Zamanian-Daryoush, H. Nie, A. M. Silva, B. R. G. Williams, and X. Li Poly(dI{middle dot}dC)-induced Toll-like Receptor 3 (TLR3)-mediated Activation of NFkappa B and MAP Kinase Is through an Interleukin-1 Receptor-associated Kinase (IRAK)-independent Pathway Employing the Signaling Components TLR3-TRAF6-TAK1-TAB2-PKR J. Biol. Chem., May 2, 2003; 278(19): 16713 - 16719. [Abstract] [Full Text] [PDF] |
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J. L. Curtis and A. Punturieri Enhancing Antitumor Immunity Perioperatively: A Matter of Timing, Cooperation, and Specificity Am. J. Respir. Cell Mol. Biol., May 1, 2003; 28(5): 541 - 545. [Full Text] [PDF] |
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K. Shingu, C. Kruschinski, A. Luhrmann, K. Grote, T. Tschernig, S. von Horsten, and R. Pabst Intratracheal Macrophage-Activating Lipopeptide-2 Reduces Metastasis in the Rat Lung Am. J. Respir. Cell Mol. Biol., March 1, 2003; 28(3): 316 - 321. [Abstract] [Full Text] [PDF] |
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J.-Y. Choe, B. Crain, S. R. Wu, and M. Corr Interleukin 1 Receptor Dependence of Serum Transferred Arthritis Can be Circumvented by Toll-like Receptor 4 Signaling J. Exp. Med., February 17, 2003; 197(4): 537 - 542. [Abstract] [Full Text] [PDF] |
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M. T. Harte, I. R. Haga, G. Maloney, P. Gray, P. C. Reading, N. W. Bartlett, G. L. Smith, A. Bowie, and L. A.J. O'Neill The Poxvirus Protein A52R Targets Toll-like Receptor Signaling Complexes to Suppress Host Defense J. Exp. Med., February 3, 2003; 197(3): 343 - 351. [Abstract] [Full Text] [PDF] |
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T. Morichika, H. K. Takahashi, H. Iwagaki, T. Yoshino, R. Tamura, M. Yokoyama, S. Mori, T. Akagi, M. Nishibori, and N. Tanaka Histamine Inhibits Lipopolysaccharide-Induced Tumor Necrosis Factor-{alpha} Production in an Intercellular Adhesion Molecule-1- and B7.1-Dependent Manner J. Pharmacol. Exp. Ther., February 1, 2003; 304(2): 624 - 633. [Abstract] [Full Text] [PDF] |
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M. Yamamoto, S. Sato, K. Mori, K. Hoshino, O. Takeuchi, K. Takeda, and S. Akira Cutting Edge: A Novel Toll/IL-1 Receptor Domain-Containing Adapter That Preferentially Activates the IFN-{beta} Promoter in the Toll-Like Receptor Signaling J. Immunol., December 15, 2002; 169(12): 6668 - 6672. [Abstract] [Full Text] [PDF] |
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K. Takeda, O. Takeuchi, and S. Akira Recognition of lipopeptides by Toll-like receptors Innate Immunity, December 1, 2002; 8(6): 459 - 463. [Abstract] [PDF] |
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T. Liu, T. Matsuguchi, N. Tsuboi, T. Yajima, and Y. Yoshikai Differences in Expression of Toll-Like Receptors and Their Reactivities in Dendritic Cells in BALB/c and C57BL/6 Mice Infect. Immun., December 1, 2002; 70(12): 6638 - 6645. [Abstract] [Full Text] [PDF] |
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D. Schilling, K. Thomas, K. Nixdorff, S. N. Vogel, and M. J. Fenton Toll-Like Receptor 4 and Toll-IL-1 Receptor Domain-Containing Adapter Protein (TIRAP)/Myeloid Differentiation Protein 88 Adapter-Like (Mal) Contribute to Maximal IL-6 Expression in Macrophages J. Immunol., November 15, 2002; 169(10): 5874 - 5880. [Abstract] [Full Text] [PDF] |
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T. Ogawa, Y. Asai, M. Hashimoto, O. Takeuchi, T. Kurita, Y. Yoshikai, K. Miyake, and S. Akira Cell activation by Porphyromonas gingivalis lipid A molecule through Toll-like receptor 4- and myeloid differentiation factor 88-dependent signaling pathway Int. Immunol., November 1, 2002; 14(11): 1325 - 1332. [Abstract] [Full Text] [PDF] |
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A. E. Medvedev, A. Lentschat, L. M. Wahl, D. T. Golenbock, and S. N. Vogel Dysregulation of LPS-Induced Toll-Like Receptor 4-MyD88 Complex Formation and IL-1 Receptor-Associated Kinase 1 Activation in Endotoxin-Tolerant Cells J. Immunol., November 1, 2002; 169(9): 5209 - 5216. [Abstract] [Full Text] [PDF] |
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E. Kopp and R. Medzhitov A Plague on Host Defense J. Exp. Med., October 21, 2002; 196(8): 1009 - 1012. [Full Text] [PDF] |
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H. Takada, S. Yokoyama, and Shuhua Yang Mini-review: Enhancement of endotoxin activity by muramyldipeptide Innate Immunity, October 1, 2002; 8(5): 337 - 342. [Abstract] [PDF] |
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K. Hoshino, T. Kaisho, T. Iwabe, O. Takeuchi, and S. Akira Differential involvement of IFN-{beta} in Toll-like receptor-stimulated dendritic cell activation Int. Immunol., October 1, 2002; 14(10): 1225 - 1231. [Abstract] [Full Text] [PDF] |
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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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J. H. Wang, M. Doyle, B. J. Manning, Q. Di Wu, S. Blankson, and H. P. Redmond Induction of Bacterial Lipoprotein Tolerance Is Associated with Suppression of Toll-like Receptor 2 Expression J. Biol. Chem., September 20, 2002; 277(39): 36068 - 36075. [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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S. A. Leigh and K. S. Wise Identification and Functional Mapping of the Mycoplasma fermentans P29 Adhesin Infect. Immun., September 1, 2002; 70(9): 4925 - 4935. [Abstract] [Full Text] [PDF] |
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T. Into, M. Fujita, T. Okusawa, A. Hasebe, M. Morita, and K.-I. Shibata Synergic Effects of Mycoplasmal Lipopeptides and Extracellular ATP on Activation of Macrophages Infect. Immun., July 1, 2002; 70(7): 3586 - 3591. [Abstract] [Full Text] [PDF] |
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A. Luhrmann, U. Deiters, J. Skokowa, M. Hanke, J. E. Gessner, P. F. Muhlradt, R. Pabst, and T. Tschernig In Vivo Effects of a Synthetic 2-Kilodalton Macrophage-Activating Lipopeptide of Mycoplasma fermentans after Pulmonary Application Infect. Immun., July 1, 2002; 70(7): 3785 - 3792. [Abstract] [Full Text] [PDF] |
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