DIFFERENTIAL DENDRITIC CELL RESPONSE TO FUNGAL CELL WALL MANNANS

Abstract

Mannan in fungal cell wall plays a crucial role in the activation of innate immunity, however it has not been studied how different mannan structure involves in innate immune responses. Thus, this study aims to investigate the effects of Saccharomyces cerevisiae possessing different cell wall mannan structures on dendritic cells (DCs) responses. Bone marrow-derived dendritic cells (BM-DCs) were stimulated with heat-killed S. cerevisiae Wt and mutants that lack of the single gene involving in each step of mannosylation. Then, mRNA expression of T helper lymphocyte (Th)-inducing cytokines was determined by quantitative real-time PCR. The results demonstrated that S. cerevisiae mnn1Δ, lacking of α-1,3 mannan, notably enhanced the expression of Th-1 inducing cytokines, Il12a and Ifng, while mnn2Δ, lacking of α-1,3 and α-1,2 mannan, significantly increased Ifng expression in BM-DCs when compared to Wt. Furthermore, BM-DCs stimulated with och1Δ, which N-linked mannan was absence, showed the significant increase in Il1a, Il1b, and Il23a, the cytokines involving in Th17 induction and amplification respectively. The data suggested that the different mannan structures affected DC responses, which may consequently influence Th differentiation. This knowledge will be beneficial for the development of carbohydrate adjuvants in the future.