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

Florian Heil, Hiroaki Hemmi, Hubertus Hochrein, Franziska Ampenberger, Carsten Kirschning, Shizuo Akira, Grayson Lipford, Hermann Wagner, Stefan Bauer, Florian Heil, Hiroaki Hemmi, Hubertus Hochrein, Franziska Ampenberger, Carsten Kirschning, Shizuo Akira, Grayson Lipford, Hermann Wagner, Stefan Bauer

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.

Source: PubMed

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