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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 »
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. 
