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Science 303 (5663): 1526-1529

Copyright © 2004 by the American Association for the Advancement of Science

Species-Specific Recognition of Single-Stranded RNA via Toll-like Receptor 7 and 8

Florian Heil,1* Hiroaki Hemmi,2* Hubertus Hochrein,1 Franziska Ampenberger,1 Carsten Kirschning,1 Shizuo Akira,2,3 Grayson Lipford,4 Hermann Wagner,1 Stefan Bauer1{dagger}

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.

1 Institute of Medical Microbiology, Immunology and Hygiene, Technische Universität München, Trogerstr. 9, D - 81675 Munich, Germany.
2 Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
3 ERATO, Japan Science and Technology Corporation, Osaka 565-0047, Japan.
4 Coley Pharmaceutical Group, Inc., 93 Worcester Street, Suite 101, Wellesley, MA 02481, USA

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* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: stefan.bauer{at}

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I. Jelinek, J. N. Leonard, G. E. Price, K. N. Brown, A. Meyer-Manlapat, P. K. Goldsmith, Y. Wang, D. Venzon, S. L. Epstein, and D. M. Segal (2011)
J. Immunol. 186, 2422-2429
   Abstract »    Full Text »    PDF »
RIG-I-Mediated Antiviral Signaling Is Inhibited in HIV-1 Infection by a Protease-Mediated Sequestration of RIG-I.
M. Solis, P. Nakhaei, M. Jalalirad, J. Lacoste, R. Douville, M. Arguello, T. Zhao, M. Laughrea, M. A. Wainberg, and J. Hiscott (2011)
J. Virol. 85, 1224-1236
   Abstract »    Full Text »    PDF »
Macrophages recognize streptococci through bacterial single-stranded RNA.
S. D. Deshmukh, B. Kremer, M. Freudenberg, S. Bauer, D. T. Golenbock, and P. Henneke (2011)
EMBO Rep. 12, 71-76
   Abstract »    Full Text »    PDF »
Blood Myeloid Dendritic Cells from HIV-1-Infected Individuals Display a Proapoptotic Profile Characterized by Decreased Bcl-2 Levels and by Caspase-3+ Frequencies That Are Associated with Levels of Plasma Viremia and T Cell Activation in an Exploratory Study.
S. M. Dillon, L. J. Friedlander, L. M. Rogers, A. L. Meditz, J. M. Folkvord, E. Connick, M. D. McCarter, and C. C. Wilson (2011)
J. Virol. 85, 397-409
   Abstract »    Full Text »    PDF »
The TLR7 Agonist R848 Alleviates Allergic Inflammation by Targeting Invariant NKT Cells To Produce IFN-{gamma}.
F. Grela, A. Aumeunier, E. Bardel, L. P. Van, E. Bourgeois, J. Vanoirbeek, M. Leite-de-Moraes, E. Schneider, M. Dy, A. Herbelin, et al. (2011)
J. Immunol. 186, 284-290
   Abstract »    Full Text »    PDF »
Plasmacytoid dendritic cells sense skin injury and promote wound healing through type I interferons.
J. Gregorio, S. Meller, C. Conrad, A. Di Nardo, B. Homey, A. Lauerma, N. Arai, R. L. Gallo, J. DiGiovanni, and M. Gilliet (2010)
J. Exp. Med. 207, 2921-2930
   Abstract »    Full Text »    PDF »
The Innate Immune Adaptor Molecule MyD88 Restricts West Nile Virus Replication and Spread in Neurons of the Central Nervous System.
K. J. Szretter, S. Daffis, J. Patel, M. S. Suthar, R. S. Klein, M. Gale Jr., and M. S. Diamond (2010)
J. Virol. 84, 12125-12138
   Abstract »    Full Text »    PDF »
The Chlamydia muridarum-Induced IFN-{beta} Response Is TLR3-Dependent in Murine Oviduct Epithelial Cells.
W. A. Derbigny, R. M. Johnson, K. S. Toomey, S. Ofner, and K. Jayarapu (2010)
J. Immunol. 185, 6689-6697
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Early Innate Recognition of Herpes Simplex Virus in Human Primary Macrophages Is Mediated via the MDA5/MAVS-Dependent and MDA5/MAVS/RNA Polymerase III-Independent Pathways.
J. Melchjorsen, J. Rintahaka, S. Soby, K. A. Horan, A. Poltajainen, L. Ostergaard, S. R. Paludan, and S. Matikainen (2010)
J. Virol. 84, 11350-11358
   Abstract »    Full Text »    PDF »
Involvement of TLR2 and TLR4 in cell responses to Rickettsia akari.
M. A. Quevedo-Diaz, C. Song, Y. Xiong, H. Chen, L. M. Wahl, S. Radulovic, and A. E. Medvedev (2010)
J. Leukoc. Biol. 88, 675-685
   Abstract »    Full Text »    PDF »

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