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

@article{citeulike:2350783, 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 immunogenicity1, 2. In the case of DNA vaccines3, 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 IB 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 sensor4). 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.}, author = {Ishii, Ken J. and Kawagoe, Tatsukata and Koyama, Shohei and Matsui, Kosuke and Kumar, Himanshu and Kawai, Taro and Uematsu, Satoshi and Takeuchi, Osamu and Takeshita, Fumihiko and Coban, Cevayir and Akira, Shizuo}, citeulike-article-id = {2350783}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nature06537}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/nature06537}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18256672}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18256672}, day = {7}, doi = {10.1038/nature06537}, issn = {1476-4687}, journal = {Nature}, keywords = {cytosolic\_receptor, dna, innate\_immunity, tbk1}, month = {February}, number = {7179}, pages = {725--729}, posted-at = {2008-07-30 03:09:44}, priority = {3}, publisher = {Nature Publishing Group}, title = {TANK-binding kinase-1 delineates innate and adaptive immune responses to DNA vaccines.}, url = {http://dx.doi.org/10.1038/nature06537}, volume = {451}, year = {2008} }

TY - JOUR ID - citeulike:2350783 L3 - citeulike-article-id:2350783 N2 - Successful vaccines contain not only protective antigen(s) but also an adjuvant component that triggers innate immune activation and is necessary for their optimal immunogenicity1, 2. In the case of DNA vaccines3, 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 IB 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 sensor4). 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. IS - 7179 JF - Nature SN - 1476-4687 EP - 729 TI - TANK-binding kinase-1 delineates innate and adaptive immune responses to DNA vaccines. PB - Nature Publishing Group VL - 451 SP - 725 KW - cytosolic_receptor KW - dna KW - innate_immunity KW - tbk1 AU - Ishii, Ken AU - Kawagoe, Tatsukata AU - Koyama, Shohei AU - Matsui, Kosuke AU - Kumar, Himanshu AU - Kawai, Taro AU - Uematsu, Satoshi AU - Takeuchi, Osamu AU - Takeshita, Fumihiko AU - Coban, Cevayir AU - Akira, Shizuo PY - 2008/02/07/ UR - http://dx.doi.org/10.1038/nature06537 ER -