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

Heil, Florian; Hemmi, Hiroaki; Hochrein, Hubertus; Ampenberger, Franziska; Kirschning, Carsten; Akira, Shizuo; Lipford, Grayson; Wagner, Hermann et al. · Science · 2004

basic_science · Level V

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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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