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Innate Antiviral Responses by Means of TLR7-Mediated Recognition of Single-Stranded RNA
Sandra S. Diebold,1Tsuneyasu Kaisho,2,3Hiroaki Hemmi,2Shizuo Akira,2,4Caetano Reis e Sousa1*
Interferons (IFNs) are critical for protection from viral infection,but the pathways linking virus recognition to IFN inductionremain poorly understood. Plasmacytoid dendritic cells producevast amounts of IFN- in response to the wild-type influenzavirus. Here, we show that this requires endosomal recognitionof influenza genomic RNA and signaling by means of Toll-likereceptor 7 (TLR7) and MyD88. Single-stranded RNA (ssRNA) moleculesof nonviral origin also induce TLR7-dependent production ofinflammatory cytokines. These results identify ssRNA as a ligandfor TLR7 and suggest that cells of the innate immune systemsense endosomal ssRNA to detect infection by RNA viruses.
1 Immunobiology Laboratory, Cancer Research UK, London Research Institute, London WC2A 3PX, UK. 2 Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Yamadaoka 3-1, Suita City, Osaka 565–0871, Japan. 3 RIKEN Research Center for Allergy and Immunology, 1-7-22 Suehiro-cho, Tsurumiku, Yokohama City, Kanagawa 230–0045, Japan. 4 Akira Innate Immunity Project, ERATO, Japan Science and Technology Corporation, Osaka 565–0871, Japan.
* To whom correspondence should be addressed. E-mail: caetano{at}cancer.org.uk
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S. L. Doyle, C. A. Jefferies, C. Feighery, and L. A. J. O'Neill (2007)
J. Biol. Chem.
282, 36953-36960
|Abstract »|Full Text »|PDF »
Differential Activation of Human Monocyte-Derived and Plasmacytoid Dendritic Cells by West Nile Virus Generated in Different Host Cells.
M. C. Silva, A. Guerrero-Plata, F. D. Gilfoy, R. P. Garofalo, and P. W. Mason (2007)
J. Virol.
81, 13640-13648
|Abstract »|Full Text »|PDF »
Development of plasmacytoid dendritic cells in bone marrow stromal cell niches requires CXCL12-CXCR4 chemokine signaling.
H. Kohara, Y. Omatsu, T. Sugiyama, M. Noda, N. Fujii, and T. Nagasawa (2007)
Blood
110, 4153-4160
|Abstract »|Full Text »|PDF »
Heterogeneity of TLR3 mRNA transcripts and responsiveness to poly (I:C) in human NK cells derived from different donors.
S. Sivori, M. Falco, S. Carlomagno, E. Romeo, L. Moretta, and A. Moretta (2007)
Int. Immunol.
19, 1341-1348
|Abstract »|Full Text »|PDF »
Modified Vaccinia Virus Ankara Induces Toll-Like Receptor-Independent Type I Interferon Responses.
Z. Waibler, M. Anzaghe, H. Ludwig, S. Akira, S. Weiss, G. Sutter, and U. Kalinke (2007)
J. Virol.
81, 12102-12110
|Abstract »|Full Text »|PDF »
Influenza Virus-Induced Type I Interferon Leads to Polyclonal B-Cell Activation but Does Not Break Down B-Cell Tolerance.
A. Woods, F. Monneaux, P. Soulas-Sprauel, S. Muller, T. Martin, A.-S. Korganow, and J.-L. Pasquali (2007)
J. Virol.
81, 12525-12534
|Abstract »|Full Text »|PDF »
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 »
in response to the wild-type influenza virus. Here, we show that this requires endosomal recognition of influenza genomic RNA and signaling by means of Toll-like receptor 7 (TLR7) and MyD88. Single-stranded RNA (ssRNA) molecules of nonviral origin also induce TLR7-dependent production of inflammatory cytokines. These results identify ssRNA as a ligand for TLR7 and suggest that cells of the innate immune system sense endosomal ssRNA to detect infection by RNA viruses. 
