Ascophyllan Purified from Ascophyllum nodosum Induces Th1 and Tc1 Immune Responses by Promoting Dendritic Cell Maturation

Abstract

Marine-derived sulfated polysaccharides have been shown to possess certain anti-virus, anti-tumor, anti-inflammatory and anti-coagulant activities. However, the in vivo immunomodulatory effects of marine-derived pure compounds have been less well characterized. In this study, we investigated the effect of ascophyllan, a sulfated polysaccharide purified from Ascophyllum nodosum, on the maturation of mouse dendritic cells (DCs) in vitro and in vivo. Ascophyllan induced up-regulation of co-stimulatory molecules and production of pro-inflammatory cytokines in bone marrow-derived DCs (BMDCs). Moreover, in vivo administration of ascophyllan promotes up-regulation of CD40, CD80, CD86, MHC class I and MHC class II and production of IL-6, IL-12 and TNF-α in spleen cDCs. Interestingly, ascophyllan induced a higher degree of co-stimulatory molecule up-regulation and pro-inflammatory cytokine production than fucoidan, a marine-derived polysaccharide with well-defined effect for promoting DC maturation. Ascophyllan also promoted the generation of IFN-γ-producing Th1 and Tc1 cells in the presence of DCs in an IL-12-dependent manner. Finally, myeloid differentiation primary response 88 (MyD88) signaling pathway was essential for DC maturation induced by ascophyllan. Taken together, these results demonstrate that ascophyllan induces DC maturation, and consequently enhances Th1 and Tc1 responses in vivo. This knowledge could facilitate the development of novel therapeutic strategies to combat infectious diseases and cancer.

Maturation of dendritic cells by pullulan promotes anti-cancer effect

“…Various polysaccharides, including fucoidan, ascophyllan and λ-carrageenan, have shown immune activation and anti-cancer effects [3, 19, 23, 24]. In this study, we showed that pullulan, a polysaccharide purified from Aureobasidium pullulans , promoted the activation of BMDCs in vitro and of spleen DCs in vivo, and induced anti-cancer immune responses.…”

“…The initial cultures were prepared as described previously [19, 33]. Bone marrow nucleated cells (1 × 10 6 cells/mL) were cultured in 5 mL modified RPMI 1640 medium containing 10% FBS in 6 well plates: 50 ng/mL rmGM-CSF plus 50 ng/mL rmIL-4 were added to the medium to support the generation of BMDCs.…”

“…Different subsets of DCs have different abilities of Ag-presentation and T cell activation. In mouse, conventional DCs (cDC) have two subsets: CD8α + CD11c + and CD8α − CD11c + cDCs [3, 19, 20]. CD8α + CD11c + cDCs are specialized in the cross-presentation of endogenously synthesized Ags through MHC class I to CTL [20, 21], and CD8α − CD11c + cDCs have the selective ability to present extracellular Ags directly through MHC class II to CD4 T cells [22].…”

The Sulfated Polysaccharides of Brown Algae and Products of Their Enzymatic Transformation as Potential Vaccine Adjuvants

“…As already mentioned above, "ideal adjuvant" has to possess immunomodulatory activity. There is a number of communications showing immunomodulatory and adjuvant activity of fucoidans depending on their structural features [6,105,116].…”

“…Results of in vivo research of the immunostimulatory and adjuvant activity of fucoidans from 4 species of brown alga A. nodosum, M. pyrifera, U. pinnatifida and F. vesiculosus are of considerable interest [105]. Authors showed that fucoidan from M. pyrifera activated DC-and NK-cells to a large extent, and also T-cells and showed stronger adjuvant effect which is expressed in strengthening of production of specific antibodies to OVA while sulfates content in its structure significantly did not differ in comparison with other fucoidans.…”