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

Science. 2004 Mar 5;303(5663):1526-9. doi: 10.1126/science.1093620. Epub 2004 Feb 19.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • HIV-1 / immunology*
  • Humans
  • Interferon-alpha / biosynthesis
  • Leukocytes, Mononuclear / immunology
  • Macrophages / immunology*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Myeloid Differentiation Factor 88
  • Oligoribonucleotides / chemistry
  • Oligoribonucleotides / immunology*
  • Quaternary Ammonium Compounds
  • RNA, Viral / chemistry
  • RNA, Viral / immunology*
  • RNA, Viral / metabolism
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Receptors, Immunologic / metabolism
  • Species Specificity
  • Thionucleotides / chemistry
  • Thionucleotides / immunology
  • Toll-Like Receptor 7
  • Toll-Like Receptor 8
  • Toll-Like Receptors
  • Transfection
  • Uridine / analysis

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, Differentiation
  • Cytokines
  • Fatty Acids, Monounsaturated
  • Interferon-alpha
  • MYD88 protein, human
  • Membrane Glycoproteins
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Oligoribonucleotides
  • Quaternary Ammonium Compounds
  • RNA, Viral
  • Receptors, Cell Surface
  • Receptors, Immunologic
  • TLR7 protein, human
  • TLR8 protein, human
  • Thionucleotides
  • Tlr7 protein, mouse
  • Toll-Like Receptor 7
  • Toll-Like Receptor 8
  • Toll-Like Receptors
  • Guanosine
  • 1,2-dioleoyloxy-3-(trimethylammonium)propane
  • Uridine