Mannan Derivatives Instruct Dendritic Cells to Induce Th1/Th2 Cells Polarization via Differential Mitogen-Activated Protein Kinase Activation.

Mannan derived from fungal cell walls have potential uses as immunomodulating agents and vaccine adjuvants. Immunization with antigen conjugated to oxidized mannan (OM) or reduced mannan (RM) have induced differential immune responses in mice. Yet, the adjuvant effect and differences in molecular profiles of OM and RM on APCs is unresolved. Here, we investigated the response of mouse bone marrow-derived DCs to OM and RM. OM and RM stimulated DCs to produce differential Th1/Th2-inducing cytokines in vitro. OM and RM-activated DCs stimulated allogeneic T-cell Th1 and Th2 polarization reaction. OM instruct DCs to stimulate Th1 responses via IL-12p70 production, which depends on the phosphorylation of p38, RM barely induce IL-12p70, but IL-10 and IL-4, and magnitude of ERK phosphorylation, which results in a Th2 bias. These findings indicate that OM and RM were potent adjuvant capable of directly initiating DC activation Th1 and Th2 polarization respectively.