Cryptococcus neoformans is an opportunistic fungal pathogen causing life-threatening meningoencephalitis in immunocompromised individuals. Several Cryptococcal mannoproteins (MPs), such as MP98 and MP84, are reported as key antigens stimulating host CD4 (+) T-cell response. Chitin deacetylase 1 (CDA1) that converts chitin into chitosan, is essential for the cell wall integrity of C. neoformans, and MP88 is a major protein associated with extracellular vesicles (EV). In this study, we investigated the structure of N-/O-glycans of Cryptococcal MPs and effect on their function on the interaction with host cells. The MP88(H) proteins with truncated N-glycans stimulated more efficiently several cytokine secretion of the dendritic cells compared to the WT-secreted MP(H)s. These results indicate that highly mannosylated N-glycans seem to hide O-glycans or specific parts of proteins, which might serve as a ligand or an epitope, recognized by receptors of mammalian cells. We also obtained the purified MP88(H) proteins with O-glycans with and without xylose, which will provide information to define the specific roles of O-glycan structures of MPs in the interaction with host cells, particularly the insights into the role of xylose conjugated O-glycan. The purified CDA1 and MP88 with the altered N-/O-glycan structures will be valuable tools to examine the relationship between glycan structure and function in adhering to host cells and inducing the cytokine secretion of host cells. The information generated by this study would deepen our understanding of glycan-based host-pathogen interaction and expect to be useful for the development of next generation antifungal drugs for fungal-specific targets.