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Originally published in Science Express on 19 February 2004
Science 5 March 2004:
Vol. 303. no. 5663, pp. 1526 - 1529
DOI: 10.1126/science.1093620
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Reports

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}

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



* These authors contributed equally to this work.

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

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Regulation of IRF-3-dependent Innate Immunity by the Papain-like Protease Domain of the Severe Acute Respiratory Syndrome Coronavirus.
S. G. Devaraj, N. Wang, Z. Chen, Z. Chen, M. Tseng, N. Barretto, R. Lin, C. J. Peters, C.-T. K. Tseng, S. C. Baker, et al. (2007)
J. Biol. Chem. 282, 32208-32221
   Abstract »    Full Text »    PDF »
Differential Type I IFN-Inducing Abilities of Wild-Type versus Vaccine Strains of Measles Virus.
M. Shingai, T. Ebihara, N. A. Begum, A. Kato, T. Honma, K. Matsumoto, H. Saito, H. Ogura, M. Matsumoto, and T. Seya (2007)
J. Immunol. 179, 6123-6133
   Abstract »    Full Text »    PDF »
HIV turns plasmacytoid dendritic cells (pDC) into TRAIL-expressing killer pDC and down-regulates HIV coreceptors by Toll-like receptor 7-induced IFN-{alpha}.
A. W. Hardy, D. R. Graham, G. M. Shearer, and J.-P. Herbeuval (2007)
PNAS 104, 17453-17458
   Abstract »    Full Text »    PDF »
Differential expression of Toll-like receptor 2 (TLR2) and responses to TLR2 ligands between human and murine vascular endothelial cells.
Shuang Chen, M. H. Wong, D. J. Schulte, M. Arditi, and K. S. Michelsen (2007)
Innate Immunity 13, 281-296
   Abstract »    PDF »
ST2 Is Essential for Th2 Responsiveness and Resistance to Pseudomonas aeruginosa Keratitis.
X. Huang, W. Du, R. P. Barrett, and L. D. Hazlett (2007)
Invest. Ophthalmol. Vis. Sci. 48, 4626-4633
   Abstract »    Full Text »    PDF »
Calcineurin Negatively Regulates TLR-Mediated Activation Pathways.
Y. J. Kang, B. Kusler, M. Otsuka, M. Hughes, N. Suzuki, S. Suzuki, W.-C. Yeh, S. Akira, J. Han, and P. P. Jones (2007)
J. Immunol. 179, 4598-4607
   Abstract »    Full Text »    PDF »
IFN Regulatory Factor Family Members Differentially Regulate the Expression of Type III IFN (IFN-{lambda}) Genes.
P. I. Osterlund, T. E. Pietila, V. Veckman, S. V. Kotenko, and I. Julkunen (2007)
J. Immunol. 179, 3434-3442
   Abstract »    Full Text »    PDF »
Toll-Like Receptors in Brain Development and Homeostasis.
P. H. Larsen, T. H. Holm, and T. Owens (2007)
Sci. STKE 2007, pe47
   Abstract »    Full Text »    PDF »
Taxol Increases the Amount and T Cell Activating Ability of Self-Immune Stimulatory Multimolecular Complexes Found in Ovarian Cancer Cells.
N. Tsuda, D. Z. Chang, T. Mine, C. Efferson, A. Garcia-Sastre, X. Wang, S. Ferrone, and C. G. Ioannides (2007)
Cancer Res. 67, 8378-8387
   Abstract »    Full Text »    PDF »
Eosinophils contribute to innate antiviral immunity and promote clearance of respiratory syncytial virus.
S. Phipps, C. E. Lam, S. Mahalingam, M. Newhouse, R. Ramirez, H. F. Rosenberg, P. S. Foster, and K. I. Matthaei (2007)
Blood 110, 1578-1586
   Abstract »    Full Text »    PDF »
Polyinosinic Acid Is a Ligand for Toll-like Receptor 3.
S. Marshall-Clarke, J. E. Downes, I. R. Haga, A. G. Bowie, P. Borrow, J. L. Pennock, R. K. Grencis, and P. Rothwell (2007)
J. Biol. Chem. 282, 24759-24766
   Abstract »    Full Text »    PDF »
Stabilized immune modulatory RNA compounds as agonists of Toll-like receptors 7 and 8.
T. Lan, E. R. Kandimalla, D. Yu, L. Bhagat, Y. Li, D. Wang, F. Zhu, J. X. Tang, M. R. Putta, Y. Cong, et al. (2007)
PNAS 104, 13750-13755
   Abstract »    Full Text »    PDF »
Tissue-Specific and Inducer-Specific Differential Induction of ISG56 and ISG54 in Mice.
F. Terenzi, C. White, S. Pal, B. R. G. Williams, and G. C. Sen (2007)
J. Virol. 81, 8656-8665
   Abstract »    Full Text »    PDF »
MyD88-Dependent Immune Activation Mediated by Human Immunodeficiency Virus Type 1-Encoded Toll-Like Receptor Ligands.
A. Meier, G. Alter, N. Frahm, H. Sidhu, B. Li, A. Bagchi, N. Teigen, H. Streeck, H.-J. Stellbrink, J. Hellman, et al. (2007)
J. Virol. 81, 8180-8191
   Abstract »    Full Text »    PDF »


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