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Innate Antiviral Responses by Means of TLR7-Mediated Recognition of Single-Stranded RNA
Sandra S. Diebold,1
Tsuneyasu Kaisho,2,3
Hiroaki Hemmi,2
Shizuo Akira,2,4
Caetano Reis e Sousa1*
Abstract:
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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84, 12011-12017
|Abstract »|Full Text »|PDF »
Intranodal Vaccination with Naked Antigen-Encoding RNA Elicits Potent Prophylactic and Therapeutic Antitumoral Immunity.
S. Kreiter, A. Selmi, M. Diken, M. Koslowski, C. M. Britten, C. Huber, O. Tureci, and U. Sahin (2010)
Cancer Res.
70, 9031-9040
|Abstract »|Full Text »|PDF »
Influenza A Infection Enhances Cross-Priming of CD8+ T Cells to Cell-Associated Antigens in a TLR7- and Type I IFN-Dependent Fashion.
J. Wei, J. Waithman, R. Lata, N. A. Mifsud, J. Cebon, T. Kay, M. J. Smyth, A. J. Sadler, and W. Chen (2010)
J. Immunol.
185, 6013-6022
|Abstract »|Full Text »|PDF »
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 »
Dissociation of Paramyxovirus Interferon Evasion Activities: Universal and Virus-Specific Requirements for Conserved V Protein Amino Acids in MDA5 Interference.
Interferon Regulatory Factor 3-Dependent Pathways Are Critical for Control of Herpes Simplex Virus Type 1 Central Nervous System Infection.
V. D. Menachery, T. J. Pasieka, and D. A. Leib (2010)
J. Virol.
84, 9685-9694
|Abstract »|Full Text »|PDF »
Innate Immune Activation in Primary HIV-1 Infection.
J. J. Chang and M. Altfeld (2010)
The Journal of Infectious Disease
202, S297-S301
|Abstract »|Full Text »|PDF »
The Absence of IDO Upregulates Type I IFN Production, Resulting in Suppression of Viral Replication in the Retrovirus-Infected Mouse.
M. Hoshi, K. Saito, A. Hara, A. Taguchi, H. Ohtaki, R. Tanaka, H. Fujigaki, Y. Osawa, M. Takemura, H. Matsunami, et al. (2010)
J. Immunol.
185, 3305-3312
|Abstract »|Full Text »|PDF »
TLR9 Contributes to the Recognition of EBV by Primary Monocytes and Plasmacytoid Dendritic Cells.
S. Fiola, D. Gosselin, K. Takada, and J. Gosselin (2010)
J. Immunol.
185, 3620-3631
|Abstract »|Full Text »|PDF »
NK Cells as Effectors of Acquired Immune Responses: Effector CD4+ T Cell-Dependent Activation of NK Cells Following Vaccination.
A. Horowitz, R. H. Behrens, L. Okell, A. R. Fooks, and E. M. Riley (2010)
J. Immunol.
185, 2808-2818
|Abstract »|Full Text »|PDF »
N. W. Lukacs, J. J. Smit, S. Mukherjee, S. B. Morris, G. Nunez, and D. M. Lindell (2010)
J. Immunol.
185, 2231-2239
|Abstract »|Full Text »|PDF »
IFN-{gamma} Primes Intact Human Coronary Arteries and Cultured Coronary Smooth Muscle Cells to Double-Stranded RNA- and Self-RNA-Induced Inflammatory Responses by Upregulating TLR3 and Melanoma Differentiation-Associated Gene 5.
U. Ahmad, R. Ali, A. H. Lebastchi, L. Qin, S.-f. L. Lo, A. O. Yakimov, S. F. Khan, J. C. Choy, A. Geirsson, J. S. Pober, et al. (2010)
J. Immunol.
185, 1283-1294
|Abstract »|Full Text »|PDF »
Dendritic Cells in Uninfected Infants Born to Hepatitis B Virus-Positive Mothers.
L. J. Koumbi, N. G. Papadopoulos, V. Anastassiadou, M. Machaira, D. A. Kafetzis, and V. Papaevangelou (2010)
Clin. Vaccine Immunol.
17, 1079-1085
|Abstract »|Full Text »|PDF »
Innate Immune Recognition in Infectious and Noninfectious Diseases of the Lung.
Characterization of human DNGR-1+ BDCA3+ leukocytes as putative equivalents of mouse CD8{alpha}+ dendritic cells.
L. F. Poulin, M. Salio, E. Griessinger, F. Anjos-Afonso, L. Craciun, J.-L. Chen, A. M. Keller, O. Joffre, S. Zelenay, E. Nye, et al. (2010)
J. Exp. Med.
207, 1261-1271
|Abstract »|Full Text »|PDF »
Particle size and activation threshold: a new dimension of danger signaling.
L. Rettig, S. P. Haen, A. G. Bittermann, L. von Boehmer, A. Curioni, S. D. Kramer, A. Knuth, and S. Pascolo (2010)
Blood
115, 4533-4541
|Abstract »|Full Text »|PDF »
Antitumor Activity and Immune Response Induction of a Dual Agonist of Toll-Like Receptors 7 and 8.
D. Wang, M. Precopio, T. Lan, D. Yu, J. X. Tang, E. R. Kandimalla, and S. Agrawal (2010)
Mol. Cancer Ther.
9, 1788-1797
|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. 
