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Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8.

Science (New York, N.Y.)

Adaptor Proteins, Signal Transducing, Animals, Antigens, Differentiation, metabolism, Base Sequence, Cytokines, biosynthesis, Dendritic Cells, immunology, Fatty Acids, Monounsaturated, Genetic Complementation Test, Guanosine, analysis, HIV-1, genetics, Humans, Interferon-alpha, Leukocytes, Mononuclear, Macrophages, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, Myeloid Differentiation Factor 88, Oligoribonucleotides, chemistry, Quaternary Ammonium Compounds, RNA, Viral, Receptors, Cell Surface, Receptors, Immunologic, Species Specificity, Thionucleotides, Toll-Like Receptor 7, Toll-Like Receptor 8, Toll-Like Receptors, Transfection, Uridine

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      Abstract

      Double-stranded ribonucleic acid (dsRNA) serves as a danger signal associated with viral infection and leads to stimulation of innate immune cells. In contrast, the immunostimulatory potential of single-stranded RNA (ssRNA) is poorly understood and innate immune receptors for ssRNA are unknown. We report that guanosine (G)- and uridine (U)-rich ssRNA oligonucleotides derived from human immunodeficiency virus-1 (HIV-1) stimulate dendritic cells (DC) and macrophages to secrete interferon-alpha and proinflammatory, as well as regulatory, cytokines. By using Toll-like receptor (TLR)-deficient mice and genetic complementation, we show that murine TLR7 and human TLR8 mediate species-specific recognition of GU-rich ssRNA. These data suggest that ssRNA represents a physiological ligand for TLR7 and TLR8.

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      Journal
      14976262
      10.1126/science.1093620

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