Abstract
The generation of cell-mediated immunity against many infectious pathogens involves the production of interleukin-12 (IL-12), a key signal of the innate immune system. Yet, for many pathogens, the molecules that induce IL-12 production by macrophages and the mechanisms by which they do so remain undefined. Here it is shown that microbial lipoproteins are potent stimulators of IL-12 production by human macrophages, and that induction is mediated by Toll-like receptors (TLRs). Several lipoproteins stimulated TLR-dependent transcription of inducible nitric oxide synthase and the production of nitric oxide, a powerful microbicidal pathway. Activation of TLRs by microbial lipoproteins may initiate innate defense mechanisms against infectious pathogens.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens, Bacterial / chemistry
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Antigens, Bacterial / immunology*
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Antigens, Bacterial / metabolism
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Cell Line
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Drosophila Proteins*
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Gene Expression Regulation
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Humans
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Interleukin-12 / biosynthesis*
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Interleukin-12 / genetics
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Lipopolysaccharides / immunology
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Lipoproteins / chemistry
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Lipoproteins / immunology*
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Lipoproteins / metabolism
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Macrophages / immunology*
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Macrophages / metabolism
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Membrane Glycoproteins / metabolism*
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Mice
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Monocytes / immunology*
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Monocytes / metabolism
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Mycobacterium tuberculosis / immunology*
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NF-kappa B / biosynthesis
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Nitric Oxide Synthase / genetics
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Nitric Oxide Synthase Type II
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Promoter Regions, Genetic
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Receptors, Cell Surface / metabolism*
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Signal Transduction
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Toll-Like Receptors
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Transcription, Genetic
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Transfection
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Tumor Cells, Cultured
Substances
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Ag38 antigen, Mycobacterium tuberculosis
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Antigens, Bacterial
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Drosophila Proteins
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Lipopolysaccharides
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Lipoproteins
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Membrane Glycoproteins
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NF-kappa B
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Receptors, Cell Surface
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Toll-Like Receptors
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Interleukin-12
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NOS2 protein, human
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type II
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Nos2 protein, mouse