TANK-binding kinase 1-dependent or -independent signaling elicits the cell-type-specific innate immune responses induced by the adenovirus vector.
Adenovirus vectors (Adv) elicit innate immune responses via several pattern-recognition receptors. Although it has been suggested that various Adv-induced mechanisms play important roles in the induction of innate immunity in vitro, the impacts of these mechanisms in vivo remain unclear. Viral nucleic acids elicit innate immune responses through the recognition of cytosolic nucleic acid sensors and transduce intracellular signals to TANK-binding kinase (TBK) 1. In this study, to determine the impacts of viral nucleic acids on innate immune responses in vivo, we administered transgene-expressing Adv to Tbk1-deficient mice. The systemic Adv administration failed to induce type I interferons (type I IFNs) in the spleen, but not the liver, of Tbk1-deficient mice, resulting in the increase of transgene-expressing cells in the spleen, but not the liver. Moreover, Adv failed to induce type I IFNs in the bone-marrow-derived dendritic cells, but not the mouse embryonic fibroblasts, from Tbk1-deficient mice in vitro. These results support the idea that Adv elicit innate immunity in immune cells and non-immune cells in a TBK1-dependent and TBK1-independent manner, respectively.
Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan.
Sayaka
S
Tsuzuki
Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan.
Masashi
M
Tachibana
Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan.
Masahisa
M
Hemmi
Laboratory of Stem Cell Regulation, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan.
Tomoko
T
Yamaguchi
Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan.
Masaki
M
Shoji
Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan Laboratory of Regulatory Sciences for Oligonucleotide Therapeutics, Clinical Drug Development Unit, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan.
Fuminori
F
Sakurai
Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan Laboratory of Vaccine Science, World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
Kouji
K
Kobiyama
Laboratory of Stem Cell Regulation, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan.
Kenji
K
Kawabata
Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan Laboratory of Vaccine Science, World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan Laboratory of Vaccine Design, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan Center for Drug Design Research, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan Department of Virology and Immunology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
Ken J
KJ
Ishii
Laboratory of Host Defense, World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan Department of Host Defense, The Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
Shizuo
S
Akira
Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan iPS Cell-Based Research Project on Hepatic Toxicity and Metabolism, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan Laboratory of Hepatocyte Regulation, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan Global Center for Medical Engineering and Informatics, Osaka University, Osaka 565-0871, Japan mizuguch@phs.osaka-u.ac.jp.
Hiroyuki
H
Mizuguchi
D000256:Adenoviridae / Q000276:immunology*; D000818:Animals; D002478:Cells, Cultured; D004279:DNA, Viral / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D005347:Fibroblasts / Q000276:immunology* / Q000821:virology; D005822:Genetic Vectors / Q000276:immunology*; D007113:Immunity, Innate; D007370:Interferon Type I / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000821:virology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009928:Organ Specificity / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D013154:Spleen / Q000276:immunology / Q000821:virology*
D004279:DNA, Viral; D007370:Interferon Type I; C498588:Tbk1 protein, mouse; D017346:Protein Serine-Threonine Kinases
gene therapy; nucleic acid sensing; type I IFN