The Adjuvant Effects of High-Molecule-Weight Polysaccharides Purified from Antrodia cinnamomea on Dendritic Cell Function and DNA Vaccines

Abstract

The biological activity of the edible basidiomycete Antrodia cinnamomea (AC) has been studied extensively. Many effects, such as anti-cancer, anti-inflammatory, and antioxidant activities, have been reported from either crude extracts or compounds isolated from AC. However, research addressing the function of AC in enhancing immunity is rare. The aim of the present study is to investigate the active components and the mechanism involved in the immunostimulatory effect of AC. We found that polysaccharides (PS) in the water extract of AC played a major role in dendritic cell (DC) activation, which is a critical leukocyte in initiating immune responses. We further size purified and identified that the high-molecular weight PS fraction (greater than 100 kDa) exhibited the activating effect. The AC high-molecular weight PSs (AC hmwPSs) promoted pro-inflammatory cytokine production by DCs and the maturation of DCs. In addition, DC-induced antigen-specific T cell activation and Th1 differentiation were increased by AC hmwPSs. In studying the molecular mechanism, we confirmed the activation of the MAPK and NF-κB pathways in DCs after AC hmwPSs treatment. Furthermore, we demonstrated that TLR2 and TLR4 are required for the stimulatory activity of AC hmwPSs on DCs. In a mouse tumor model, we demonstrated that AC hmwPSs enhanced the anti-tumor efficacy of the HER-2/neu DNA vaccine by facilitating specific Th1 responses. Thus, we conclude that hmwPSs are the major components of AC that stimulate DCs via the TLR2/TLR4 and NF-κB/MAPK signaling pathways. The AC hmwPSs have potential to be applied as adjuvants.

Effects of Taiwanofungus camphoratus on non-specific and specific immune activities in mice

“…Most of these findings indicated polysaccharides from T. camphoratus mycelium had the great potential to develop as immunomodulatory agent to treat infection disease or as a vaccine adjuvant for cancer therapy (Chen et al 2008; Cheng et al 2008; Kuo et al 2008; Lin et al 2015). In this study, we found LAC, composed of solid-state cultivated powder of T. camphoratus , had the ability to regulate non-specific and specific immune response.…”

“…It grows on the inner cavity of Cinnamomum kanehirae Hayata (Lauraceae) and has been used to promote health, treat liver disease, drug and food intoxication, hangover, exhaustion and cancers by the aboriginals in Taiwan for a long time (Wu SHR and Chang 1997; Geethangili and Tzeng 2011; Yue et al 2012). Several bioactive compounds of T. camphoratus have been identified and the biological functions in immunomodulatory (Song et al 2014; Kuo et al 2008; Sheu et al 2009), anticancer (Huang et al 2015; Kumar et al 2015; Lin et al 2015), antiinflammation (Chen YF et al 2014; Hsieh et al 2010), antioxidant (Wu MD et al 2011; Hseu et al 2008) and hepatoprotective (Huang CH et al 2010; Gokila Vani et al 2014; Chang et al 2016) effects were widely studied.…”

Dendritic cell vaccines: A review of recent developments and their potential pediatric application

“…52,53 In one study of naturally occurring plant polysaccharides used in ancient Chinese medicine, intraperitoneal injections of extracts from Antrodia cinnamomea were shown to enhance DC activation in vivo, with increased T H 1 T cells as well as increased native CD11c C DC's in tumor draining lymph nodes. 47 In another study, vaccination with DC that were stimulated in vitro with a combination of extracts from Astragalus membranaceous and Colonopsis pilosulae resulted in increased tumor control in an in vivo murine breast cancer model. 46 Three additional studies showed that in vitro pre-treatment of tumor antigen pulsed DC with uric acid, 48 g-glutamic acid, 49 or pancreatic adenocarcinoma upregulated factor (PAUF), a protein naturally secreted by human pancreatic carcinomas, 51 resulted in tumor shrinkage in murine tumor models.…”

“…Other recently published work has focused on the use of novel adjuvants from natural sources, [46][47][48][49] known recall antigens, 50 tumor derived immunogenic proteins, 51 or proprietary costimulatory mixtures. 52,53 In one study of naturally occurring plant polysaccharides used in ancient Chinese medicine, intraperitoneal injections of extracts from Antrodia cinnamomea were shown to enhance DC activation in vivo, with increased T H 1 T cells as well as increased native CD11c C DC's in tumor draining lymph nodes.…”

“…In three of these cases, adjuvant activity was definitively shown to activate the TLR pathway in DC. 47,49,51 More study is needed, however, because the role of TLR in DC activation has been extensively and recently reviewed 40,54 and one theme that has emerged is that TLR activation in murine models cannot be easily extrapolated to human models because murine and human DC constitutively express a different overlapping set of TLR. DC, exposed to antigen can be matured in vitro or in vivo.…”