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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 Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan; ERATO, Japan Science and Technology Corporation, Japan. 4 Coley Pharmaceutical Group, Inc., 93 Worcester Street, Suite 101, Wellesley, MA 02481, USA.
* To whom correspondence should be addressed. E-mail: stefan.bauer{at}lrz.tum.de.
Double-stranded ribonucleic acid (dsRNA) serves as a dangersignal associated with viral infection and leads to stimulationof innate immune cells. In contrast, the immunostimulatory potentialof single-stranded RNA (ssRNA) is poorly understood and innateimmune receptors for ssRNA are unknown. We report that guanosine(G)- and uridine (U)-rich ssRNA oligonucleotides derived fromhuman immunodeficiency virus-1 (HIV-1) stimulate dendritic cells(DC) and macrophages to secrete interferon- and proinflammatory,as well as regulatory, cytokines. Using Toll-like receptor (TLR)-deficientmice and genetic complementation, we show that murine TLR7 andhuman TLR8 mediate species-specific recognition of GU-rich ssRNA.These data suggest that ssRNA represents a physiological ligandfor TLR7 and TLR8.
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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 »
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.
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)
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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 »
and proinflammatory, as well as regulatory, cytokines. 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.
