Journal ArticleDOI
IRF-7 is the master regulator of type-I interferon-dependent immune responses
Kenya Honda,Hideyuki Yanai,Hideo Negishi,Masataka Asagiri,Mitsuharu Sato,Tatsuaki Mizutani,Naoya Shimada,Yusuke Ohba,Yusuke Ohba,Akinori Takaoka,Nobuaki Yoshida,Tadatsugu Taniguchi +11 more
TLDR
It is shown that mice deficient in the Irf7 gene are more vulnerable than Myd88-/- mice to viral infection, and this correlates with a marked decrease in serum IFN levels, indicating the importance of the IRF-7-dependent induction of systemic IFN responses for innate antiviral immunity.Abstract:
The type-I interferon (IFN-alpha/beta) response is critical to immunity against viruses and can be triggered in many cell types by cytosolic detection of viral infection, or in differentiated plasmacytoid dendritic cells by the Toll-like receptor 9 (TLR9) subfamily, which generates signals via the adaptor MyD88 to elicit robust IFN induction. Using mice deficient in the Irf7 gene (Irf7-/- mice), we show that the transcription factor IRF-7 is essential for the induction of IFN-alpha/beta genes via the virus-activated, MyD88-independent pathway and the TLR-activated, MyD88-dependent pathway. Viral induction of MyD88-independent IFN-alpha/beta genes is severely impaired in Irf7-/- fibroblasts. Consistently, Irf7-/- mice are more vulnerable than Myd88-/- mice to viral infection, and this correlates with a marked decrease in serum IFN levels, indicating the importance of the IRF-7-dependent induction of systemic IFN responses for innate antiviral immunity. Furthermore, robust induction of IFN production by activation of the TLR9 subfamily in plasmacytoid dendritic cells is entirely dependent on IRF-7, and this MyD88-IRF-7 pathway governs the induction of CD8+ T-cell responses. Thus, all elements of IFN responses, whether the systemic production of IFN in innate immunity or the local action of IFN from plasmacytoid dendritic cells in adaptive immunity, are under the control of IRF-7.read more
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Journal ArticleDOI
Pathogen Recognition and Innate Immunity
TL;DR: New insights into innate immunity are changing the way the way the authors think about pathogenesis and the treatment of infectious diseases, allergy, and autoimmunity.
Journal ArticleDOI
Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses
Hiroki Kato,Osamu Takeuchi,Shintaro Sato,Mitsutoshi Yoneyama,Masahiro Yamamoto,Kosuke Matsui,Satoshi Uematsu,Andreas Jung,Taro Kawai,Ken Ishii,Osamu Yamaguchi,Kinya Otsu,Tohru Tsujimura,Chang-Sung Koh,Caetano Reis e Sousa,Yoshiharu Matsuura,Takashi Fujita,Shizuo Akira +17 more
TL;DR: It is found that RIG-I is essential for the production of interferons in response to RNA viruses including paramyxoviruses, influenza virus and Japanese encephalitis virus, whereas MDA5 is critical for picornavirus detection.
Journal ArticleDOI
Identification and Characterization of MAVS, a Mitochondrial Antiviral Signaling Protein that Activates NF-κB and IRF3
TL;DR: The identification of a novel protein termed MAVS (mitochondrial antiviral signaling), which mediates the activation of NF-kappaB and IRF 3 in response to viral infection, and implicates a new role of mitochondria in innate immunity.
Journal ArticleDOI
Pathogen Recognition and Inflammatory Signaling in Innate Immune Defenses
TL;DR: This review presents current knowledge on pathogen recognition through different families of PRRs and the increasingly complex signaling pathways responsible for activation of an inflammatory and antimicrobial response and medical implications are discussed.
Journal ArticleDOI
Toll-like receptor signaling pathways.
Takumi Kawasaki,Taro Kawai +1 more
TL;DR: Recent progress is described in the understanding of TLR signaling regulation and its contributions to host defense.
References
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Species-Specific Recognition of Single-Stranded RNA via Toll-like Receptor 7 and 8
Florian Heil,Hiroaki Hemmi,Hubertus Hochrein,Franziska Ampenberger,Carsten J. Kirschning,Shizuo Akira,Grayson B. Lipford,Hermann Wagner,Stefan Bauer +8 more
TL;DR: It is shown that guanosine (G)- and uridine (U)-rich ssRNA oligonucleotides derived from human immunodeficiency virus–1 (HIV-1) stimulate dendritic cells and macrophages to secrete interferon-α and proinflammatory, as well as regulatory, cytokines, and these data suggest that ssRNA represents a physiological ligand for TLR7 and TLR8.
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The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses.
Mitsutoshi Yoneyama,Mika Kikuchi,Takashi Natsukawa,Noriaki Shinobu,Tadaatsu Imaizumi,Makoto Miyagishi,Kazunari Taira,Shizuo Akira,Takashi Fujita +8 more
TL;DR: In this article, the authors identify retinoic acid inducible gene I (RIG-I), which encodes a DExD/H box RNA helicase that contains a caspase recruitment domain, as an essential regulator for dsRNA-induced signaling.
Journal ArticleDOI
Cpg motifs in bacterial dna trigger direct b-cell activation
Arthur M. Krieg,Ae-Kyung Yi,Sara Matson,Thomas J. Waldschmidt,Gail A. Bishop,Gail A. Bishop,Rebecca M. Teasdale,Gary A. Koretzky,Dennis M. Klinman +8 more
TL;DR: The potent immune activation by CpG oligon nucleotides has impli-cations for the design and interpretation of studies using 'antisense' oligonucleotides and points to possible new applications as adjuvants.
Journal ArticleDOI
Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA.
TL;DR: 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.
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Toll-like receptors in innate immunity.
Kiyoshi Takeda,Shizuo Akira +1 more
TL;DR: Toll-like receptors-mediated activation of innate immunity controls not only host defense against pathogens but also immune disorders, and the involvement of TLR-mediated pathways in autoimmune and inflammatory diseases has been proposed.