Curdlan activates dendritic cells through dectin-1 and toll-like receptor 4 signaling

Curdlan, a β-1,3-glucan isolated from Alcaligenes faecalis, is an agonist of Dectin-1 in various immune cells, including dendritic cells (DCs). However, whether curdlan also activates DCs through Other receptors remains unknown. In this study, we found that curdlan activates DCs through Dectin-1 and Toll-like Receptor 4 (TLR4). Curdlan increased the expression levels of surface molecules (CD40, CD80, CD86, and MHC-I/II), the production of cytokines (IL-12, IL-1β, TNF-α, and IFN-β), migration toward MIP-3β, and allogeneic T cell stimulation activity of DCs. Curdlan increased the phosphorylation of Syk, Raf-1, Akt, MAPKs, IKK, and NF-κB p65 in DCs. However, curdlan only slightly activated DCs transfected with small interfering RNAs against Dectin-1 or TLR4 and C3H/HeJ DCs, which have non-functional TLR4, in comparison with control DCs. Curdlan increased antitumor activity of DCs in a syngeneic tumor model. In summary, our data show that curdlan activates DCs through Dectin-1 and TLR4 signaling and the combination of curdlan and DCs efficiently inhibit tumor growth in mice.

Adjuvant; C3H/HeJ; Cancer immunotherapy; siRNA.