Induction of dendritic cell maturation by β-glucan isolated from Sparassis crispa

Sparassis crispa is a medicinal mushroom containing high 6-branched 1,3-β-D-glucan (sparan) content, which exhibits immune-mediated antitumor activity. In the present study, we investigated the stimulating effect of sparan on phenotypic and functional maturation of dendritic cells (DCs). Phenotypic maturation was confirmed by the elevated expressions of CD40, CD80, CD86, and MHC-I/II molecules. Functional activation was proved by increased cytokine production of IL-12, IL-1β, TNF-α, and IFN-α/β, enhanced IL-2 production and proliferation of allogenic T cells, and decreased endocytosis. The role of toll-like receptor 4 (TLR4) as a membrane receptor of sparan was proved by the impaired maturation of DCs generated from bone marrow cells of tlr4−/− knock-out mice and TLR4-mutated C3H/HeJ mice, and by using anti-MD-2/TLR4 neutralizing antibody. Sparan increased phosphorylation of ERK, p38, and JNK, and enhanced nuclear translocation of NF-κB p50/p65 in DCs. These results indicate that sparan activates DCs via MAPK and NF-κB signaling pathways, which are signaling molecules downstream of TLR4.

Research highlights► b-glucan sparan induces phenotypic and functional maturation of dendritic cells. ► Sparan uses toll-like receptor 4 as one of the membrane receptors. ► Sparan induces phosphorylation of ERK, JNK, and p38 MAPKs. ► Sparan increases nuclear translocation of NF-kB p50/p65.