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Activation of myeloid dendritic cells by deoxynucleic acids from Cordyceps sinensis via a Toll-like receptor 9-dependent pathway |
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| Authors: | Gang Xiao Akiko Miyazato Yuzuru Abe Tiantuo Zhang Ken Inden Daiki Tanno Keiko Ishii Shizuo Akira Yoichiro Iwakura Naohito Ohno Hiroyuki Kunishima Mitsuo Kaku |
| Affiliation: | a Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan b Department of Infection Control and Laboratory Diagnostics, Internal Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan c Division of Respiratory Diseases, Department of Internal Medicine, The 3rd Affiliated Hospital of Sun Yat-sen University, 600 Tian He Road, Guangzhou 510630, PR China d Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan e Department of Host Defense, Research Institute for Microbial Disease, Osaka University, Suita, Osaka 565-0871, Japan f Center for Experimental Medicine, Department of Microbiology and Immunology, The Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan g Laboratory for Immunopharmacology of Microbial Products, Tokyo University of Pharmacy and Life Science, Hachioji, Tokyo 192-0392, Japan |
| 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-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. |
| Keywords: | Cordyceps sinensis DNA Dendritic cells TLR9 Cytokines CD40 |
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