Elsevier

Cellular Immunology

Volume 281, Issue 2, February 2013, Pages 111-121
Cellular Immunology

Enhancement of the immune responses to foot-and-mouth disease vaccination in mice by oral administration of a Novel polysaccharide from the roots of Radix Cyathulae officinalis Kuan (RC)

https://doi.org/10.1016/j.cellimm.2013.02.004Get rights and content

Highlights

  • RCPS improved the humoral and cellular immune response.

  • RCPS up-regulated antigen specific cytokine expression.

  • RCPS enhanced in vivo CTL response and NK cell activity.

  • RCPS induced DCs’ maturation and decreased Treg frequency.

Abstract

Foot-and-mouth disease (FMD) is a kind of the important animal infectious disease caused by the foot-and-mouth disease virus (FMDV). Thus, the aim of this study was to determine the effects of the polysaccharide from the Radix Cyathulae officinalis Kuan (RCPS) for its adjuvant potential on the FMDV-specific cellular and humoral immune responses in mice. In this study, our findings shows that oral administration of RCPS significantly enhanced the phagocytic capacity of peritoneal macrophage, splenocyte proliferation, the activity of natural killer (NK) cells and cytotoxic T lymphocytes (CTL) and IgG, IgG1, IgG2a, and IgG2b antibody titers. Furthermore, RCPS promoted the level of IL-2, IFN-γ and IL-4 in CD4+T cells and level of IFN-γ in CD8+T cells. In addition, RCPS enhanced the expression of CD40+, CD80+ and CD86+ on DCs. Importantly, RCPS could up-regulated the mRNA level of MHC I, MHC II, TLR-2, TLR-4. Interestingly, RCPS down-regulated the frequency of CD4+CD25+Foxp3+Treg cells. Taken together, these results demonstrate that RCPS can enhance both cellular and humoral immune responses via up-regulating DCs maturation through TLR2, TLR4 signaling pathway, and suppressing Treg frequency.

Introduction

FMD is one of the most contiguous and economically devastating viral diseases of cloven-hoofed animals such as cattle, swine and sheep in the worldwide [1], [2]. Because FMDV can rapidly spread between susceptible animals, it is listed as one of the most important animal diseases by the World Organization for Animal Health (OIE) [3]. To date, the widespread vaccination with inactivated FMDV is the only practical strategy to control the epidemic in most developing countries [4]. However, failure to convey protection is often reported in recent years [5], [6], [7]. Adjuvant has long been considered as an important strategy to improve currently vaccine efficacy against FMDV infection [8]. Unfortunately, the potent adjuvant action is often associated with the higher toxicity, as exemplified by the case of Freund’s complete adjuvant (FCA) [9]. Growing evidences have proved that Chinese herbal medicine (CHMs) and ingredients possess the immune-enhancing function. So, many investigators tried to use medicinal herbs as the adjuvant of vaccines and have made much progress [10], [11]. Chinese herbal medicinal adjuvant possesses some advantages, such as abundant natural resources, reliable efficacy, lower side-effects and toxicity.

Most polysaccharides derived from higher plants are relatively nontoxic and do not cause significant side effects, which is a major problem with immunomodulatory bacterial polysaccharides and synthetic compounds. Thus, the plant polysaccharides are recognized as an effective biological response modifier with low toxicity [12].

Recently, many polysaccharides from CHMs have been reported to possess adjuvant potential on the specific cellular and humoral immune responses against pathogens and vaccines [13], [14], [15], [16], [17]. Particular advantages of the plant polysaccharide adjuvants are excellent safety, tolerability, and easy of manufacture and formulation. Thus, the plant polysaccharide adjuvants have enormous potential on using vaccines against both pathogens and cancer [18]. Cyathula officinalis (Amaranthaceae family), as one of the widely used medicinal herbs, is a perennial herbaceous plant which widely distributes in tropical areas of Asia and Africa, particularly in China, Korea and Vietnam. Its root (“Chuan Niu Xi” in Chinese, C. officinalis kuan) is a kind of commonly-used Chinese traditional herbal medicine with a wide range of pharmacological activities [19]. It is usually used as a tonic, emmenagogue, antiarthritic, diuretic, and antifertility agent to nourish the liver and kidneys, strengthen bones and muscles, invigorate circulation [19]. The modern pharmacological studies demonstrated that the root of C. officinalis possessed immunostimulant [20], [21], uteri-excitant and antifertility [22], [23], antitumor [24], [25], analgestic, antibacterial, anti-inflammatory [26] and antisenile [27].

In this study, we attempted to evaluate the effects of oral administration of the isolated polysaccharide (RCPS) on the humoral and cellular immune responses in ICR mice. The results indicated that RCPS could improve the immune response to the FMD vaccination by via up-regulating the DC maturation and decreasing the frequency of Treg frequency.

Section snippets

Materials

Goat anti-mouse IgG, IgG1, IgG2a and IgG2b peroxidase conjugate were from Santa Cruz Biotechnology Inc (California, USA). Concanavalin A (ConA), Propidium Iodide (PI), RPMI-1640 medium, and goat anti-mouse IgG peroxidase conjugate were purchased from Sigma Chemical Co. (Saint Louis, Missouri, USA). Cell Counting kit-8 (CCK-8) was purchased from Beyotime Institute of Biotechonology (Haimen, Jiangsu, China). Fetal calf serum (FCS) was provided by Invitrogen Gibco Biotechnology Inc. (California,

FMDV-specific IgG and the IgG isotypes

To evaluate the adjuvant effect of RCPS on the humoral immune responses, IgG and the IgG subclasses were measured by an indirect ELISA. As Fig. 1(A) showed that FMDV-specific IgG titers were significantly higher in mice orally administered RCPS at a dose of 25 and 100 mg than that in mice administered saline solution only (p < 0.05). More over, 50 mg RCPS in the vaccinated mice induced the highest IgG titer among all the groups. Besides, all IgG isotypes in the vaccinated mice treated by RCPS were

Discussion

The immune response of the host to the antigen includes both the cellular and humoral immunity. The humoral immune response induced by B cells is characterized by the specific antigen antibody reaction. Cell-mediated immune defense plays an important role in combating the intracellular microbe infections which mediated specifically by T cells [40]. Among the T-lymphocytes, the helper T cells induce B-lymphocytes to secrete antibodies, and cytotoxic T-lymphocytes help phagocytes to destroy

Acknowledgments

This study was supported by two-side support plan of Sichuan Agricultural University (00770107) and was supported in part by Sichuan Science and Technology Commission (Project No. 2012HH0013), and by Open Foundation in Sichuan Key Laboratory of Meat Processing (Project No.13-R04).

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    These authors contributed equally to the work.

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