title: CpG-A stimulates Hsp72 secretion from plasmacytoid dendritic cells, facilitating cross-presentation.
abstract: Plasmacytoid dendritic cells (pDCs) are the main producers of IFN-α in response to unmethylated DNA molecules, including cytosine guanine dinucleotide (CpG)-DNA in vivo. pDCs specifically express toll-like receptor (TLR) 9 and are therefore able to recognize the unmethylated DNAs. It has recently been shown that not only conventional DCs (cDCs) but also pDCs efficiently cross-present exogenous antigens after TLR9 activation. However, the precise molecular mechanism has remained unclear. Here, we show that pDCs secreted heat shock protein 72 (Hsp72) in response to CpG-A administration in a TLR9-dependent manner. Extracellular Hsp72 bound to an Hsp90-peptide complex and enhanced binding of Hsp90-peptide complex to pDC, resulting in efficient cross-presentation. Our experiments therefore suggest a mechanism for orchestration of immune responses by stimulation of pDCs with CpG-A.
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan; United Graduate School of Veterinary Sciences, Yamaguchi University, Yamaguchi, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Kajiwara
authors.affiliation: Department of Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Goro
authors.initials: G
authors.lastname: Kutomi
authors.affiliation: Department of Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Kurotaki
authors.affiliation: Department of Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Saito
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kanaseki
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tsukahara
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hirohashi
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Torigoe
authors.affiliation: Department of Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirata
authors.affiliation: Joint Department of Veterinary Medicine, Tottori University, Tottori, Japan.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Okamoto
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan; Department of Molecular Therapeutics, Center for Food & Medical Innovation, Hokkaido University, Sapporo, Japan. Electronic address: ytamura@gmail.com.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Tamura
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D046912:Multiprotein Complexes; D009838:Oligodeoxyribonucleotides / Q000276:immunology* / Q000494:pharmacology; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000941:Antigens; D050884:HSP72 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D008024:Ligands; D046912:Multiprotein Complexes; D009838:Oligodeoxyribonucleotides; D010455:Peptides; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha
keywords: Antigen presentation/processing; Dendritic cells; Heat shock protein; T cells; Tumor immunity