Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bacterial Proteins / immunology*
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Cells, Cultured
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Drosophila Proteins*
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Humans
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Interleukin-12 / biosynthesis
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Interleukin-6 / biosynthesis
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Lipopeptides
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Lipoproteins / immunology*
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Macrophages, Peritoneal / cytology
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Macrophages, Peritoneal / immunology
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / immunology
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Mice
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Mice, Inbred A
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Mice, Inbred C57BL
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Mice, Knockout
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NF-kappa B / metabolism
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Nitric Oxide / biosynthesis
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Oligopeptides / immunology*
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / immunology*
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Signal Transduction / immunology
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Toll-Like Receptor 2
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Toll-Like Receptor 6
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Toll-Like Receptors
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Tumor Necrosis Factor-alpha / biosynthesis
Substances
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Bacterial Proteins
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Drosophila Proteins
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Interleukin-6
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Lipopeptides
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Lipoproteins
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Membrane Glycoproteins
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NF-kappa B
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Oligopeptides
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Receptors, Cell Surface
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TLR2 protein, human
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TLR6 protein, human
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Tlr6 protein, mouse
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Toll-Like Receptor 2
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Toll-Like Receptor 6
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Toll-Like Receptors
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Tumor Necrosis Factor-alpha
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Interleukin-12
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Nitric Oxide
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macrophage stimulatory lipopeptide 2