Cordlan Polysaccharide Isolated from Mushroom Cordyceps Militaris Induces Dendritic Cell Maturation Through Toll-like Receptor 4 Signalings

Defect of dendritic cell (DC) maturation in tumor microenvironments is an important immunological problem limiting the success of cancer immunotherapy. Here, we investigated the effects of polysaccharide (cordlan) isolated from Cordyceps militaris on DC maturation. Phenotypic maturation of DCs by cordlan was demonstrated by the elevated expressions of CD40, CD80, CD86, MHC-I, and MHC-II molecules, and functional maturation by increased expression of IL-12, IL-1beta, TNF-alpha, and IFN-alphabeta, enhanced allogenic T cell stimulation, and decreased endocytosis. Of note was that cordlan induced maturation of tlr4+/+ DCs from C3H/HeN mice, but not tlr4(-/-) DCs from C3H/HeJ mice, suggesting the promising membrane receptor of cordlan. In addition, cordlan increased phosphorylation of ERK, p38, and JNK, and nuclear translocation of NF-kappaB p50/p65, which were main signaling molecules down-stream from TLR4. These results indicate that cordlan induces DC maturation through TLR4 signaling pathways.