Abstract

Fucoidan, a sulfated polysaccharide purified from brown algae, has a variety of immune-modulation effects, including promoting antigen uptake and enhancing anti-viral and anti-tumor effects. However, the effect of fucoidan in vivo, especially its adjuvant effect on in vivo anti-tumor immune responses, was not fully investigated. In this study, we investigated the effect of fucoidan on the function of spleen dendritic cells (DCs) and its adjuvant effect in vivo. Systemic administration of fucoidan induced up-regulation of CD40, CD80 and CD86 expression and production of IL-6, IL-12 and TNF-α in spleen cDCs. Fucoidan also promoted the generation of IFN-γ-producing Th1 and Tc1 cells in an IL-12-dependent manner. When used as an adjuvant in vivo with ovalbumin (OVA) antigen, fucoidan promoted OVA-specific antibody production and primed IFN-γ production in OVA-specific T cells. Moreover, fucoidan enhanced OVA-induced up-regulation of MHC class I and II on spleen cDCs and strongly prompted the proliferation of OVA-specific CD4 and CD8 T cells. Finally, OVA immunization with fucoidan as adjuvant protected mice from the challenge with B16-OVA tumor cells. Taken together, these results suggest that fucoidan can function as an adjuvant to induce Th1 immune response and CTL activation, which may be useful in tumor vaccine development.

Highlights

  • Dendritic cells (DCs) are professional antigen presenting cells (APCs) and key modulators of T- and B-cell immunity mainly owing to their superior ability to take up and present antigens [1,2]

  • Fucoidan promotes maturation of spleen conventional DCs (cDCs) Previously we have showed that fucoidan can induce maturation of human peripheral blood DCs (PBDCs) [23]

  • We examined the effect of fucoidan on CD8a+ and CD8a2 cDC subpopulations 24 hrs after injection of fucoidan

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Summary

Introduction

Dendritic cells (DCs) are professional antigen presenting cells (APCs) and key modulators of T- and B-cell immunity mainly owing to their superior ability to take up and present antigens [1,2]. CD8a+ conventional DCs (cDCs), a minor population among total mouse spleen DCs, have the selective ability to cross-present exogenous antigens to induce cytotoxic T cell (CTL) activation [3,4,5]. DCs can directly sense pathogen components by pattern recognition receptors (PRRs), such as toll like receptors (TLRs), scavenger receptors (SRs), Ctype lectins, mannose receptors and complement receptors [7]. The activation of these receptors induces signal events that regulate the expression of pro-inflammatory and immune mediators [7,8,9]

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