Abstract
Toll-like receptors (TLRs) play a fundamental role in the recognition of bacteria and viruses. TLR3 is activated by viral dsRNA and polyinosinic-polycytidylic acid (poly(I:C)), a synthetic mimetic of viral RNA. We show that NK cells, known for their capacity to eliminate virally infected cells, express TLR3 and up-regulate TLR3 mRNA upon poly(I:C) stimulation. Treatment of highly purified NK cells with poly(I:C) significantly augments NK cell-mediated cytotoxicity. Poly(I:C) stimulation also leads to up-regulation of activation marker CD69 on NK cells. Furthermore, NK cells respond to poly(I:C) by producing proinflammatory cytokines like IL-6 and IL-8, as well as the antiviral cytokine IFN-gamma. The induction of cytokine production by NK cells was preceded by activation of NF-kappaB. We conclude that the ability of NK cells to directly recognize and respond to viral products is important in mounting effective antiviral responses.
MeSH terms
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Adjuvants, Immunologic / pharmacology
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Antigen-Presenting Cells / immunology*
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Antigens, CD / biosynthesis
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Antigens, Differentiation, T-Lymphocyte / biosynthesis
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Cells, Cultured
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Cytokines / biosynthesis
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Cytotoxicity Tests, Immunologic
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Cytotoxicity, Immunologic / drug effects
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Humans
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Interferon Type I / biosynthesis
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Interferon Type I / physiology
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Killer Cells, Natural / drug effects
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / metabolism*
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Lectins, C-Type
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Lymphocyte Activation* / drug effects
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Lymphocyte Activation* / immunology
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Membrane Glycoproteins / agonists*
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Membrane Glycoproteins / biosynthesis
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Membrane Glycoproteins / genetics
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NF-kappa B / metabolism
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NF-kappa B / physiology
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Poly I-C / pharmacology
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RNA, Double-Stranded / pharmacology
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RNA, Double-Stranded / physiology*
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RNA, Messenger / biosynthesis
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Receptors, Cell Surface / agonists*
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Receptors, Cell Surface / biosynthesis
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Receptors, Cell Surface / genetics
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Signal Transduction / drug effects
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Signal Transduction / immunology
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Toll-Like Receptor 3
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Toll-Like Receptors
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Up-Regulation / drug effects
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Up-Regulation / immunology
Substances
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Adjuvants, Immunologic
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Antigens, CD
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Antigens, Differentiation, T-Lymphocyte
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CD69 antigen
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Cytokines
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Interferon Type I
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Lectins, C-Type
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Membrane Glycoproteins
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NF-kappa B
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RNA, Double-Stranded
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RNA, Messenger
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Receptors, Cell Surface
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TLR3 protein, human
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Toll-Like Receptor 3
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Toll-Like Receptors
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Poly I-C