Journal ArticleDOI
TANK-binding kinase-1 delineates innate and adaptive immune responses to DNA vaccines
Ken Ishii,Tatsukata Kawagoe,Shohei Koyama,Kosuke Matsui,Himanshu Kumar,Taro Kawai,Satoshi Uematsu,Osamu Takeuchi,Fumihiko Takeshita,Cevayir Coban,Shizuo Akira +10 more
TLDR
It is demonstrated in vivo that TANK-binding kinase 1 (TBK1), a non-canonical IκB kinase, mediates the adjuvant effect of DNA vaccines and is essential for its immunogenicity in mice.Abstract:
Successful vaccines contain not only protective antigen(s) but also an adjuvant component that triggers innate immune activation and is necessary for their optimal immunogenicity. In the case of DNA vaccines, this consists of plasmid DNA; however, the adjuvant element(s) as well as its intra- and inter-cellular innate immune signalling pathway(s) leading to the encoded antigen-specific T- and B-cell responses remain unclear. Here we demonstrate in vivo that TANK-binding kinase 1 (TBK1), a non-canonical IkappaB kinase, mediates the adjuvant effect of DNA vaccines and is essential for its immunogenicity in mice. Plasmid-DNA-activated, TBK1-dependent signalling and the resultant type-I interferon receptor-mediated signalling was required for induction of antigen-specific B and T cells, which occurred even in the absence of innate immune signalling through a well known CpG DNA sensor-Toll-like receptor 9 (TLR9) or Z-DNA binding protein 1 (ZBP1, also known as DAI, which was recently reported as a potential B-form DNA sensor). Moreover, bone-marrow-transfer experiments revealed that TBK1-mediated signalling in haematopoietic cells was critical for the induction of antigen-specific B and CD4(+) T cells, whereas in non-haematopoietic cells TBK1 was required for CD8(+) T-cell induction. These data suggest that TBK1 is a key signalling molecule for DNA-vaccine-induced immunogenicity, by differentially controlling DNA-activated innate immune signalling through haematopoietic and non-haematopoietic cells.read more
Citations
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The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors
Taro Kawai,Shizuo Akira +1 more
TL;DR: Recent advances that have been made by research into the role of TLR biology in host defense and disease are described.
Journal ArticleDOI
Pattern Recognition Receptors and Inflammation
Osamu Takeuchi,Shizuo Akira +1 more
TL;DR: The role of PRRs, their signaling pathways, and how they control inflammatory responses are discussed.
Journal ArticleDOI
Toll-like Receptors and Their Crosstalk with Other Innate Receptors in Infection and Immunity
Taro Kawai,Shizuo Akira +1 more
TL;DR: The role played by TLRs in mounting protective immune responses against infection and their crosstalk with other PRRs with respect to pathogen recognition is focused on.
Journal ArticleDOI
AIM2 recognizes cytosolic dsDNA and forms a caspase-1 activating inflammasome with ASC
Veit Hornung,Veit Hornung,Andrea Ablasser,Andrea Ablasser,Marie Charrel-Dennis,Franz Bauernfeind,Franz Bauernfeind,Gabor Horvath,Daniel R. Caffrey,Eicke Latz,Katherine A. Fitzgerald +10 more
TL;DR: Using mouse and human cells, the PYHIN (pyrin and HIN domain-containing protein) family member absent in melanoma 2 (AIM2) is identified as a receptor for cytosolic DNA, which regulates caspase-1.
Journal ArticleDOI
STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity
TL;DR: It is shown that STING (stimulator of interferon genes) is critical for the induction of IFN by non-CpG intracellular DNA species produced by various DNA pathogens after infection.
References
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Hiroaki Hemmi,Osamu Takeuchi,Taro Kawai,Tsuneyasu Kaisho,Shintaro Sato,Hideki Sanjo,Makoto Matsumoto,Katsuaki Hoshino,Hermann Wagner,Kiyoshi Takeda,Shizuo Akira +10 more
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Journal ArticleDOI
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Akinori Takaoka,ZhiChao Wang,Myoung Kwon Choi,Hideyuki Yanai,Hideo Negishi,Tatsuma Ban,Yan Lu,Makoto Miyagishi,Tatsuhiko Kodama,Kenya Honda,Yusuke Ohba,Tadatsugu Taniguchi +11 more
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Journal ArticleDOI
DNA vaccines: immunology, application, and optimization*.
TL;DR: This review focuses on the mechanisms by which DNA vaccines elicit immune responses, and a list of potential applications in a variety of preclinical models is provided.