title: Baculovirus directly activates murine NK cells via TLR9.
abstract: The importance of natural killer (NK) cells in innate immune responses against tumors or viral infections enhances the appeal of NK cell-based immunotherapeutic approaches. We have recently reported that baculovirus (BV)-infected dendritic cells (DCs; BV-DCs) induce antitumor immunity against established tumors in mice. These antitumor effects were CD8+T-cell and NK cell dependent; however, they were found to be CD4+T-cell independent. In this study, we investigated the involvement of Toll-like receptor 9 (TLR9) in the process of BV recognition by NK cells. We found that BV directly stimulated NK cells, induced the expression of the activation marker CD69 and promoted interferon-gamma (IFN-γ) production and cytotoxicity. Moreover, TLR9 knockout in mice (tlr9-/- NK cells) inhibited NK cell responses to BV, indicating that TLR9 may have a relevant role in the BV-induced upregulation of NK cell functions. Our data demonstrated for the first time that NK cells directly recognize BV via TLR9, which provides opportunities for the use of this technique as an effective tool for BV-based immunotherapies against malignancies.
authors.affiliation: Department of Life and Environmental Sciences, Chiba Institute of Technology, Narashino, Chiba, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Moriyama
authors.affiliation: Department of Life and Environmental Sciences, Chiba Institute of Technology, Narashino, Chiba, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Life and Environmental Sciences, Chiba Institute of Technology, Narashino, Chiba, Japan.
authors.forename: M O
authors.initials: MO
authors.lastname: Chang
authors.affiliation: Department of Immunology and Pathology, Research Institute National Center for Global Health and Medicine, Ichikawa, Chiba, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kitajima
authors.affiliation: Research Institute, Chiba Institute of Technology, Narashino, Chiba, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Takaku
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D016367:Baculoviridae / Q000276:immunology*; D005260:Female; D007167:Immunotherapy; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000276:immunology*; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D007371:Interferon-gamma; D037181:Lectins, C-Type; D051217:Toll-Like Receptor 9; D000099192:CD69 Antigens; C000611649:IFNG protein, mouse; C495370:Tlr9 protein, mouse