Protein-bound polysaccharide activates dendritic cells and enhances OVA-specific T cell response as vaccine adjuvant

被引:30
作者
Engel, Abbi L. [1 ]
Sun, Guan-Cheng [1 ]
Gad, Ekram [2 ]
Rastetter, Lauren R. [2 ]
Strobe, Katie [1 ]
Yang, Yi [2 ]
Dang, Yushe [2 ]
Disis, Mary L. [2 ]
Lu, Hailing [2 ]
机构
[1] Bastyr Univ, Kenmore, WA 98028 USA
[2] Univ Washington, Tumor Vaccine Grp, Ctr Translat Med Womens Hlth, Seattle, WA 98109 USA
关键词
PSK; Dendritic cells; Vaccine; OVA peptide; TOLL-LIKE RECEPTORS; COLORECTAL-CANCER; TLR2; AGONIST; BETA; IMMUNOCHEMOTHERAPY; ANTIGEN; INDUCTION; ANTIBODY; LYMPHOCYTES; ENGAGEMENT;
D O I
10.1016/j.imbio.2013.05.001
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Protein-bound polysaccharide-K (PSK) is a hot water extract from Trametes versicolor mushroom. It has been used traditionally in Asian countries for its immune stimulating and anti-cancer effects. We have recently found that PSI( can activate Toll-like receptor 2(TLR2). TLR2 is highly expressed on dendritic cells (DC), so the current study was undertaken to evaluate the effect of PSK on DC activation and the potential of using PSI as a vaccine adjuvant. In vitro experiments using mouse bone marrow-derived DC (BMDC) demonstrated that PSK induces DC maturation as shown by dose-dependent increase in the expression of CD80, CD86, MHCII, and CD40. PSK also induces the production of multiple inflammatory cytokines by DC, including IL-12, TNF-alpha, and IL-6, at both mRNA and protein levels. In vivo experiments using PSK as an adjuvant to OVAp323-339 vaccine showed that PSK as adjuvant leads to enlarged draining lymph nodes with higher number of activated DC. PSK also stimulates proliferation of OVA-specific T cells, and induces T cells that produce multiple cytokines, IFN-gamma, IL-2, and TNF-alpha. Altogether, these results demonstrate the ability of PSK to activate DC in vitro and in vivo and the potential of using PSK as a novel vaccine adjuvant. (C) 2013 Elsevier GmbH. All rights reserved.
引用
收藏
页码:1468 / 1476
页数:9
相关论文
共 44 条
[1]   Vaccine adjuvants revisited [J].
Aguilar, J. C. ;
Rodriguez, E. G. .
VACCINE, 2007, 25 (19) :3752-3762
[2]   TLR2-activated human langerhans cells promote Th17 polarization via IL-1β, TGF-β and IL-23 [J].
Aliahmadi, Ehsan ;
Gramlich, Robert ;
Gruetzkau, Andreas ;
Hitzler, Manuel ;
Krueger, Melanie ;
Baumgrass, Ria ;
Schreiner, Maximilian ;
Wittig, Burghardt ;
Wanner, Reinhard ;
Peiser, Matthias .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2009, 39 (05) :1221-1230
[3]   Engagement of Toll-like receptor-2 on cytotoxic T-lymphocytes occurs in vivo and augments antitumor activity [J].
Asprodites, Nicole ;
Zheng, Liqin ;
Geng, Degui ;
Velasco-Gonzalez, Cruz ;
Sanchez-Perez, Luis ;
Davila, Eduardo .
FASEB JOURNAL, 2008, 22 (10) :3628-3637
[4]   Immunobiology of dendritic cells [J].
Banchereau, J ;
Briere, F ;
Caux, C ;
Davoust, J ;
Lebecque, S ;
Liu, YT ;
Pulendran, B ;
Palucka, K .
ANNUAL REVIEW OF IMMUNOLOGY, 2000, 18 :767-+
[5]   A role for dendritic cells in the priming of antigen-specific CD4+ and CD8+ T lymphocytes by immune-stimulating complexes in vivo [J].
Beacock-Sharp, H ;
Donachie, AM ;
Robson, NC ;
Mowat, AM .
INTERNATIONAL IMMUNOLOGY, 2003, 15 (06) :711-720
[6]   Dectin-1 is a major β-glucan receptor on macrophages [J].
Brown, GD ;
Taylor, PR ;
Reid, DM ;
Willment, JA ;
Williams, DL ;
Martinez-Pomares, L ;
Wong, SYC ;
Gordon, S .
JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 196 (03) :407-412
[7]   Dectin-1 mediates the biological effects of β-glucans [J].
Brown, GD ;
Herre, J ;
Williams, DL ;
Willment, JA ;
Marshall, ASJ ;
Gordon, S .
JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 197 (09) :1119-1124
[8]   A TLR2 agonist is a more effective adjuvant for a Chlamydia major outer membrane protein vaccine than ligands to other TLR and NOD receptors [J].
Cheng, Chunmei ;
Jain, Pooja ;
Bettahi, Ilham ;
Pal, Sukumar ;
Tifrea, Delia ;
de la Maza, Luis M. .
VACCINE, 2011, 29 (38) :6641-6649
[9]  
Cheng K.F., 2008, Cancer Ther, V6, P117
[10]   Soluble Proteins Induce Strong CD8+ T Cell and Antibody Responses through Electrostatic Association with Simple Cationic or Anionic Lipopeptides That Target TLR2 [J].
Chua, Brendon Y. ;
Pejoski, David ;
Turner, Stephen J. ;
Zeng, Weiguang ;
Jackson, David C. .
JOURNAL OF IMMUNOLOGY, 2011, 187 (04) :1692-1701