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.
Florian Heil  1 Hiroaki Hemmi Hubertus Hochrein Franziska Ampenberger Carsten Kirschning Shizuo Akira Grayson Lipford Hermann Wagner Stefan Bauer
Affiliations
  • 1. Institute of Medical Microbiology, Immunology and Hygiene, Technische Universität München, Trogerstr. 9, D - 81675 Munich, Germany.
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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