Beta-(1 -> 4)-Mannobiose Acts As An Immunostimulatory Molecule In Murine Dendritic Cells By Binding The Tlr4/Md-2 Complex

Some beta-mannans, including those in coffee bean and soy, contain a mannose backbone with beta-(1 -> 4) bonds. Such mannooligosaccharides could have immunological functions involving direct interaction with immune cells, in addition to acting as prebiotics. This study aimed at assessing the immunological function of mannooligosaccharides with beta-(1 -> 4) bond, and elucidating their mechanism of action using bone marrow-derived murine dendritic cells (BMDCs). When BMDCs were stimulated with the mannooligosaccharides, only beta-Man-(1 -> 4)-Man significantly induced production of cytokines that included IL-6, IL-10, TNF-alpha, and IFN-beta, and enhanced CD4(+) T-cell stimulatory capacity. Use of putative receptor inhibitors revealed the binding of beta-Man-(1 -> 4)-Man to TLR4/MD2 complex and involvement with the complement C3a receptor (C3aR) for BMDC activation. Interestingly, beta-Man-(1 -> 4)-Man prolonged the production of pro-inflammatory cytokines (IL-6 and TNF-alpha), but not of the IL-10 anti-inflammatory cytokine during extended culture of BMDCs, associated with high glucose consumption. The results suggest that beta-Man-(1 -> 4)-Man is an immunostimulatory molecule, and that the promotion of glycolysis could be involved in the production of pro-inflammatory cytokine in beta-Man-(1 -> 4)-Man-stimulated BMDCs. This study could contribute to development of immune-boosting functional foods and a novel vaccine adjuvant.