title: Activation of myeloid dendritic cells by deoxynucleic acids from Cordyceps sinensis via a Toll-like receptor 9-dependent pathway.
abstract: The mechanism by which host cells recognize Cordyceps sinensis, a Chinese herbal medicine that is known to exhibit immunomodulating activity, remains poorly understood. In this study, we investigated whether the DNA of this fungus could activate mouse bone marrow-derived dendritic cells (BM-DCs). Upon stimulation with C. sinensis DNA, BM-DCs released IL-12p40 and TNF-alpha and expressed CD40. Cytokine production and CD40 expression were attenuated by chloroquin and bafilomycin A. Activation of BM-DCs by C. sinensis DNA was almost completely abrogated in TLR9KO mice. According to a luciferase reporter assay, C. sinensis DNA activated NF-kappaB in HEK293T cells transfected with the TLR9 gene. Finally, a confocal microscopic analysis showed that C. sinensis DNA was co-localized with CpG-ODN and partly with TLR9 and LAMP-1, a late endosomal marker, in BM-DCs. Our results demonstrated that C. sinensis DNA caused activation of BM-DCs in a TLR9-dependent manner.
authors.affiliation: Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan.
authors.forename: Gang
authors.initials: G
authors.lastname: Xiao
authors.forename: Akiko
authors.initials: A
authors.lastname: Miyazato
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Abe
authors.forename: Tiantuo
authors.initials: T
authors.lastname: Zhang
authors.forename: Kiwamu
authors.initials: K
authors.lastname: Nakamura
authors.forename: Ken
authors.initials: K
authors.lastname: Inden
authors.forename: Misuzu
authors.initials: M
authors.lastname: Tanaka
authors.forename: Daiki
authors.initials: D
authors.lastname: Tanno
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Miyasaka
authors.forename: Keiko
authors.initials: K
authors.lastname: Ishii
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takeda
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Shinobu
authors.initials: S
authors.lastname: Saijo
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Adachi
authors.forename: Naohito
authors.initials: N
authors.lastname: Ohno
authors.forename: Natsuo
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kunishima
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Hirakata
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Kaku
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kawakami
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003001:Cloning, Molecular; D032661:Cordyceps / Q000235:genetics; D004247:DNA / Q000494:pharmacology*; D004271:DNA, Fungal / Q000494:pharmacology*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000276:immunology*; D015854:Up-Regulation; D047071:beta-Glucans / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D004271:DNA, Fungal; D051217:Toll-Like Receptor 9; D047071:beta-Glucans; D004247:DNA; C033363:beta-1,3-glucan