Abstract
beta-Defensins are small antimicrobial peptides of the innate immune system produced in response to microbial infection of mucosal tissue and skin. We demonstrate that murine beta-defensin 2 (mDF2beta) acts directly on immature dendritic cells as an endogenous ligand for Toll-like receptor 4 (TLR-4), inducing up-regulation of costimulatory molecules and dendritic cell maturation. These events, in turn, trigger robust, type 1 polarized adaptive immune responses in vivo, suggesting that mDF2beta may play an important role in immunosurveillance against pathogens and, possibly, self antigens or tumor antigens.
Publication types
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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, Neoplasm / immunology
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Cancer Vaccines / immunology
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Cell Line
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Cytokines / biosynthesis
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Dendritic Cells / immunology*
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Drosophila Proteins*
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Female
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Humans
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Interferon-alpha / physiology
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Ligands
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Lipopolysaccharides / immunology
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Lipopolysaccharides / pharmacology
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Lymphocyte Culture Test, Mixed
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / physiology*
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C3H
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Mice, Inbred C57BL
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Neoplasms / immunology
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Neoplasms / therapy
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Receptors, CCR6
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / physiology*
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Receptors, Chemokine / metabolism
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Recombinant Fusion Proteins / pharmacology
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Signal Transduction
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Toll-Like Receptor 4
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Toll-Like Receptors
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Transfection
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beta-Defensins / pharmacology
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beta-Defensins / physiology*
Substances
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Antigens, Neoplasm
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CCR6 protein, human
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Cancer Vaccines
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Cytokines
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DEFB4A protein, human
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Drosophila Proteins
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Interferon-alpha
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Ligands
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Lipopolysaccharides
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Membrane Glycoproteins
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Receptors, CCR6
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Receptors, Cell Surface
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Receptors, Chemokine
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Recombinant Fusion Proteins
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TLR4 protein, human
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Toll-Like Receptor 4
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Toll-Like Receptors
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beta-Defensins