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Evidence-Based Complementary and Alternative Medicine
Volume 2013, Article ID 761454, 15 pages
http://dx.doi.org/10.1155/2013/761454
Research Article

Clitocybe nuda Activates Dendritic Cells and Acts as a DNA Vaccine Adjuvant

1Plant Pathology Division, Taiwan Agricultural Research Institute (TARI), Council of Agriculture (COA), Executive Yuan, Wufeng 413, Taiwan
2Graduate Institute of Immunology, National Taiwan University, Taipei 112, Taiwan
3Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu 300, Taiwan
4Institute of Biomedical Science, National Chung-Hsing University, Taichung 402, Taiwan
5Faculty of Medicine, National Yang-Ming University, Taipei 112, Taiwan
6Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung 407, Taiwan
7Division of Chest Medicine, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan
8Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan
9Department of Medical Research and Education, Taichung Veterans General Hospital, Taichung 407, Taiwan

Received 8 March 2013; Revised 25 May 2013; Accepted 1 June 2013

Academic Editor: Andreas Sandner-Kiesling

Copyright © 2013 Mei-Hsing Chen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

This work represents the first evaluation of the effects of water extract of C. nuda (WE-CN), an edible mushroom, on murine bone marrow-derived dendritic cells (BMDCs) and the potential pathway through which the effects are mediated. Our experimental results show that WE-CN could induce phenotypic maturation of DCs, as shown by the increased expression of MHC and costimulatory molecules. In addition, it also induced the proinflammatory cytokines expression on DCs and enhanced both the proliferation and IFN-γ secretion of allogenic T cells. Therefore, since WE-CN did not induce maturation of DCs generated from mice with mutated TLR-4 or TLR-2, suggesting that TLR4 and TLR2 might function as membrane receptors for WE-CN. Moreover, the mechanism of action of WE-CN may be mediated by increased phosphorylation of ERK, p38, and JNK mitogen-activated protein kinase (MAPK) and increased NF-κB p65 activity, which are important signaling molecules downstream of TLR-4 and TLR-2. Finally, coimmunization of mice with WE-CN and a HER-2/neu DNA vaccine induced a HER-2/neu-specific Th1 response that resulted in significant inhibition of HER-2/neu overexpressing mouse bladder tumor (MBT-2) growth. These data suggest that WE-CN induces DC maturation through TLR-4 and/or TLR-2 and that WE-CN can be used as an adjuvant in cancer vaccine immunotherapy.