TANK-binding kinase-1 delineates innate and adaptive immune responses to DNA vaccines

Ken J. Ishii, Tatsukata Kawagoe, shohei Koyama, Kosuke Matsui, Himanshu Kumar, Taro Kawai, Satoshi Uemasu, Osamu Takeuchi, Fumihiko Takeshita, Ceyayir Coban, Shizuo Akira

Nature 45, 725-730(2008)

Speaker: 張竣泓                          Time: 15:00~16:00, May 07, 2008

Commentator: 楊倍昌 老師                Place: Room 601

Abstract:

Effective vaccines not only offer protective antigens for adaptive immune recognition, but also need adjuvant elements that trigger innate immunity to induce the long-term protective immunity against given pathogens. In the DNA vaccines, microbial unmethylated CpG motifs in the plasmid backbone that could active innate immunity through TLR9 have been though to be an effective adjuvant. However, recent studies shown DNA vaccines still work well in TLR9-deficient mice, thus suggest there must have another pathway participate in the immunogenicity of DNA vaccines. Authors found that TANK-binding kinase-1(TBK1) is the key molecule that mediates the adjuvant role of the DNA vaccines in mice. Administration of plasmid DNA into mice activate TBK1-dependent pathway and thus trigger type 1 interferon receptor-mediated signaling that is essential for induction of antigen-specific antibody and T cells. Bone marrow transfer experiments also indicates that lack of TBK1 signaling in haematopoietic cells would impair the induction of B cells and CD4⁺ T cells and that lack of TBK1 signaling in haematopoietic cells would impair the induction of CD8⁺ T cells. Furthermore, authors found that TBK1 activating signaling was neither triggered by known TLR9- and ZBP1-mediated DNA recognition nor TLR3-, TLR7/8- and RIG-I/MDA5-mediated RNA recognition. Thus it means that there is an unknown DNA sensor(s) mediating this DNAactivated, TBK1 mediated innate activation towards adaptive response.

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