Abstract
Type I interferons (IFN) are well studied cytokines with anti-viral and immune-modulating functions. Type I IFNs are produced following viral infections, but until recently, the mechanisms of viral recognition leading to IFN production were largely unknown. Toll like receptors (TLRs) have emerged as key transducers of type I IFN during viral infections by recognizing various viral components. Furthermore, much progress has been made in defining the signaling pathways downstream of TLRs for type I IFN production. TLR7 and TLR9 have become apparent as universally important in inducing type I IFN during infection with most viruses, particularly by plasmacytoid dendritic cells. New intracellular viral pattern recognition receptors leading to type I IFN production have been identified. Many bacteria can also induce the up-regulation of these cytokines. Interestingly, recent studies have found a detrimental effect on host cells if type I IFN is produced during infection with the intracellular gram-positive bacterial pathogen, Listeria monocytogenes. This review will discuss the recent advances made in defining the signaling pathways leading to type I IFN production.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
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Review
MeSH terms
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Animals
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Bacterial Infections / physiopathology*
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DEAD Box Protein 58
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DEAD-box RNA Helicases
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DNA-Binding Proteins / metabolism
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Humans
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I-kappa B Kinase
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Interferon Regulatory Factor-3
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Interferon Regulatory Factor-7
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Interferon Type I / biosynthesis
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Interferon Type I / physiology*
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Membrane Glycoproteins / physiology
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Muromegalovirus / immunology
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Orthomyxoviridae / immunology
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Protein Serine-Threonine Kinases / metabolism
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RNA Helicases / metabolism
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Receptors, Cell Surface / physiology
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Receptors, Immunologic
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Simplexvirus / immunology
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Toll-Like Receptor 7
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Toll-Like Receptor 9
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Toll-Like Receptors
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Transcription Factors / metabolism
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Vesicular stomatitis Indiana virus / immunology
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Virus Diseases / physiopathology*
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eIF-2 Kinase / physiology
Substances
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DNA-Binding Proteins
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IRF3 protein, human
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IRF7 protein, human
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Interferon Regulatory Factor-3
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Interferon Regulatory Factor-7
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Interferon Type I
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Membrane Glycoproteins
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Receptors, Cell Surface
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Receptors, Immunologic
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TLR7 protein, human
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TLR9 protein, human
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Toll-Like Receptor 7
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Toll-Like Receptor 9
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Toll-Like Receptors
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Transcription Factors
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Protein Serine-Threonine Kinases
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TBK1 protein, human
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eIF-2 Kinase
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I-kappa B Kinase
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RIGI protein, human
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DEAD Box Protein 58
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DEAD-box RNA Helicases
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RNA Helicases