Abstract
Interferons (IFNs) are critical for protection from viral infection, but the pathways linking virus recognition to IFN induction remain poorly understood. Plasmacytoid dendritic cells produce vast amounts of IFN-alpha in response to the wild-type influenza virus. Here, we show that this requires endosomal recognition of influenza genomic RNA and signaling by means of Toll-like receptor 7 (TLR7) and MyD88. Single-stranded RNA (ssRNA) molecules of nonviral origin also induce TLR7-dependent production of inflammatory cytokines. These results identify ssRNA as a ligand for TLR7 and suggest that cells of the innate immune system sense endosomal ssRNA to detect infection by RNA viruses.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Animals
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Antigens, Differentiation / metabolism
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Cells, Cultured
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Cytokines / biosynthesis
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Dendritic Cells / immunology*
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Endocytosis
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Endosomes / immunology
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Endosomes / virology
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Genome, Viral
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Immunity, Innate*
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Influenza A virus / genetics
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Influenza A virus / immunology*
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Interferon-alpha / biosynthesis
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Ligands
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Membrane Glycoproteins / metabolism*
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Myeloid Differentiation Factor 88
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Poly U / immunology
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Polyribonucleotides / immunology
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RNA / immunology*
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RNA, Viral / immunology*
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Receptors, Cell Surface / metabolism*
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Receptors, Immunologic / metabolism
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Signal Transduction
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Toll-Like Receptor 7
Substances
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Adaptor Proteins, Signal Transducing
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Antigens, Differentiation
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Cytokines
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Interferon-alpha
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Ligands
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Membrane Glycoproteins
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Myd88 protein, mouse
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Myeloid Differentiation Factor 88
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Polyribonucleotides
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RNA, Viral
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Receptors, Cell Surface
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Receptors, Immunologic
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Tlr7 protein, mouse
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Toll-Like Receptor 7
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Poly U
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RNA