Activation of myeloid dendritic cells by deoxynucleic acids from Cordyceps sinensis via a Toll-like receptor 9-dependent pathway

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). Up...

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Bibliographic Details
Published in:Cellular immunology 2010, Vol.263 (2), p.241-250
Main Authors: Xiao, Gang, Miyazato, Akiko, Abe, Yuzuru, Zhang, Tiantuo, Nakamura, Kiwamu, Inden, Ken, Tanaka, Misuzu, Tanno, Daiki, Miyasaka, Tomomitsu, Ishii, Keiko, Takeda, Kiyoshi, Akira, Shizuo, Saijo, Shinobu, Iwakura, Yoichiro, Adachi, Yoshiyuki, Ohno, Naohito, Yamamoto, Natsuo, Kunishima, Hiroyuki, Hirakata, Yoichi, Kaku, Mitsuo, Kawakami, Kazuyoshi
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic - pharmacology
Animals
beta-Glucans - immunology
Bone marrow
CD40
Cells, Cultured
Cloning, Molecular
Cordyceps - genetics
Cordyceps sinensis
Cytokines
Dendritic cells
Dendritic Cells - cytology
Dendritic Cells - drug effects
Dendritic Cells - immunology
DNA
DNA - pharmacology
DNA, Fungal - pharmacology
Female
Flow Cytometry
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Myeloid Cells - cytology
Myeloid Cells - drug effects
Myeloid Cells - immunology
Signal Transduction - drug effects
TLR9
Toll-Like Receptor 9 - genetics
Toll-Like Receptor 9 - immunology
Up-Regulation
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Summary: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-α 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-κB 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.
ISSN:0008-8749
1090-2163
DOI:10.1016/j.cellimm.2010.04.006