International Immunology, Vol. 13, No. 7, 933-940,
July 2001
© 2001 Japanese Society for Immunology
Discrimination of bacterial lipoproteins by Toll-like receptor 6
2 Core Research for Evolutional Science and Technology (CREST) of Japan Science and Technology Corp., 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan
3 Immunobiology Research Group, Gesellschaft für Biotechnologische Forschung, Mascheroderweg 1, 38124 Braunschweig, Germany
4 Center for Microbial Pathogenesis, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA
5 Skirball Institute and Department of Microbiology, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA
Correspondence to: S. Akira
Bacterial lipoproteins (BLP) trigger immune responses via Toll-like receptor 2 (TLR2) and their immunostimulatory properties are attributed to the presence of a lipoylated N-terminus. Most BLP are triacylated at the N-terminus cysteine residue, but mycoplasmal macrophage-activating lipopeptide-2 kD (MALP-2) is only diacylated. Here we show that TLR6-deficient (TLR6–/–) cells are unresponsive to MALP-2 but retain their normal responses to lipopeptides of other bacterial origins. Reconstitution experiments in TLR2–/– TLR6–/– embryonic fibroblasts reveal that co-expression of TLR2 and TLR6 is absolutely required for MALP-2 responsiveness. Taken together, these results show that TLR6 recognizes MALP-2 cooperatively with TLR2, and appears to discriminate between the N-terminal lipoylated structures of MALP-2 and lipopeptides derived from other bacteria.
Keywords: cytokine, inflammatory mediator, knockout, macrophage, monocyte, transgenic
Transmitting editor: T. Watanabe
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|
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|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
K. Miyake Invited review: Roles for accessory molecules in microbial recognition by Toll-like receptors Innate Immunity, August 1, 2006; 12(4): 195 - 204. [Abstract] [PDF]
|
|
|
|
 |
|
 Z. Jiang, P. Georgel, C. Li, J. Choe, K. Crozat, S. Rutschmann, X. Du, T. Bigby, S. Mudd, S. Sovath, et al. Details of Toll-like receptor:adapter interaction revealed by germ-line mutagenesis PNAS, July 18, 2006; 103(29): 10961 - 10966. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. J. Brown, S. H. Sacks, and M. G. Robson Toll-Like Receptor 2 Agonists Exacerbate Accelerated Nephrotoxic Nephritis J. Am. Soc. Nephrol., July 1, 2006; 17(7): 1931 - 1939. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Henneke and R. Berner Interaction of neonatal phagocytes with group B streptococcus: recognition and response. Infect. Immun., June 1, 2006; 74(6): 3085 - 3095. [Full Text] [PDF]
|
|
|
|
|
|
N. Esen and T. Kielian Central Role for MyD88 in the Responses of Microglia to Pathogen-Associated Molecular Patterns. J. Immunol., June 1, 2006; 176(11): 6802 - 6811. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
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|
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|
 |
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 B. Schmeck, S. Huber, K. Moog, J. Zahlten, A. C. Hocke, B. Opitz, S. Hammerschmidt, T. J. Mitchell, M. Kracht, S. Rosseau, et al. Pneumococci induced TLR- and Rac1-dependent NF-{kappa}B-recruitment to the IL-8 promoter in lung epithelial cells Am J Physiol Lung Cell Mol Physiol, April 1, 2006; 290(4): L730 - L737. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
|
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|
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|
|
|
|
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|
|
|
|
|
|
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|
|
|