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). 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.
Xiao
Gang
G
Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan.
Miyazato
Akiko
A
Abe
Yuzuru
Y
Zhang
Tiantuo
T
Nakamura
Kiwamu
K
Inden
Ken
K
Tanaka
Misuzu
M
Tanno
Daiki
D
Miyasaka
Tomomitsu
T
Ishii
Keiko
K
Takeda
Kiyoshi
K
Akira
Shizuo
S
Saijo
Shinobu
S
Iwakura
Yoichiro
Y
Adachi
Yoshiyuki
Y
Ohno
Naohito
N
Yamamoto
Natsuo
N
Kunishima
Hiroyuki
H
Hirakata
Yoichi
Y
Kaku
Mitsuo
M
Kawakami
Kazuyoshi
K
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
D000276:Adjuvants, Immunologic; D004271:DNA, Fungal; D051217:Toll-Like Receptor 9; D047071:beta-Glucans; D004247:DNA; C033363:beta-1,3-glucan