Abstract
NK lymphocytes and type I IFN (IFN-alpha/beta) are major actors of the innate anti-viral response that also influence adaptive immune responses. We evaluated type I IFN production by human NK cells in response to polyI:C, a potent type I IFN-inducing TLR3 agonist. PolyI:C plus IL-2/IL-12 induced IFN-beta (but not IFN-alpha) mRNA expression and protein production by highly pure human NK cells and by the human NK cell line NK92. Neutralizing anti-IFNAR1 or anti-IFN-beta Ab prevented the production of IFN-gamma induced by polyI:C plus IL-2/IL-12. Similarly, IFN-gamma production induced by polyI:C plus IL-12 was reduced in NK cells isolated from IFNAR1(-/-) compared with WT mice. The ability of polyI:C plus IL-12 to induce IFN-gamma production was related to an increase of TLR3, Mda5 and IFNAR expression and by an increase of STAT1 and STAT4 phosphorylation. Collectively, these data demonstrate that NK cells, in response to polyI:C plus IL-2/IL-12, produce IFN-beta that induce, in an autocrine manner, the production of IFN-gamma and thereby highlight that NK cells may control the outcome of protective or injurious immune responses through type I IFN secretion.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies / immunology
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Antibodies / pharmacology
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Autocrine Communication / immunology*
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Cell Line
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Cells, Cultured
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DEAD-box RNA Helicases / genetics
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Gene Expression / drug effects
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Gene Expression / genetics
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Humans
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Interferon-Induced Helicase, IFIH1
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Interferon-beta / genetics
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Interferon-beta / immunology
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Interferon-beta / metabolism*
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Interferon-beta / pharmacology
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Interferon-gamma / genetics
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Interferon-gamma / metabolism*
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Interleukin-12 / pharmacology*
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Interleukin-2 / pharmacology*
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Killer Cells, Natural / drug effects
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Killer Cells, Natural / metabolism*
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Kinetics
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Mice
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Mice, Inbred Strains
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Mice, Knockout
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Phosphorylation / drug effects
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Poly I-C / pharmacology*
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Receptor, Interferon alpha-beta / genetics
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Receptor, Interferon alpha-beta / immunology
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Receptors, Interleukin-12 / genetics
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STAT1 Transcription Factor / metabolism
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STAT4 Transcription Factor / metabolism
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Toll-Like Receptor 3 / genetics
Substances
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Antibodies
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Interleukin-2
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Receptors, Interleukin-12
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STAT1 Transcription Factor
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STAT1 protein, human
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STAT4 Transcription Factor
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STAT4 protein, human
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TLR3 protein, human
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Toll-Like Receptor 3
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Receptor, Interferon alpha-beta
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Interleukin-12
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Interferon-beta
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Interferon-gamma
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IFIH1 protein, human
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DEAD-box RNA Helicases
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Interferon-Induced Helicase, IFIH1
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Poly I-C