There is a growing interest in polysaccharide products to be utilised as anticancer drugs, carbohydrate vaccines and health supplements. However, the precise mechanisms of their function are unclear. Gaining such knowledge is therefore vital for harnessing the power of immunomodulatory polysaccharides for improving human health. Towards this goal, scientists on the EU-funded MEDPOL (Molecular dissection of immunomodulatory function of polysaccharides) project investigated the hypothesis that polysaccharides bound to glycan-binding proteins (GBPs) expressed on the cell surface of immune cells. To this end, they developed a cell-based assay for screening the interactions of several food and microbial polysaccharides with GBPs. Results unveiled two promising polysaccharide candidates, a food polysaccharide, A (FPA), and a microbial lipopolysaccharide from the human commensal bacterium Hafnia alvei. Both polysaccharides activated dendritic cells through binding to the dendritic cell-associated lectin 2 (Dectin-2). Dectin-2 is a single transmembrane lectin expressed on various myeloid cells in mouse and man. Studies in dendritic cells deficient in Dectin-2 underscored the role of the receptor in mediating the immunomodulatory properties of the FPA polysaccharide. Further mechanistic insight into the interaction between FPA and Dectin-2 unveiled the involvement of the carbohydrate-recognition domain of Dectin-2. Overall, MEDPOL results indicate that polysaccharides activating Dectin-2 may be able to boost immune function, which will be beneficial for combating infection and cancer. The finding that polysaccharides serve as an interface in the interaction of microbes with host immune cells advances our knowledge on microbiota-host interactions and suggests that FPA could serve as an immunomodulatory prebiotic.
Immune system, polysaccharide, immunomodulatory, MEDPOL, dendritic cells, Dectin-2