Mannans are mannose polymers attached to cell wall proteins in all Candida species, including the pathogenic fungus Candida albicans. Mannans are sensed by pattern recognition receptors expressed on innate immune cells. However, the detailed structural patterns affecting immune sensing are not fully understood because mannans have a complex structure that includes α- and β-mannosyl linkages. In this study, we focused on the β-1,2-mannosides of N-linked mannan in C. albicans because this moiety is not present in the non-pathogenic yeast Saccharomyces cerevisiae. To investigate the impact of β-1,2-mannosides on immune sensing, we constructed a C. albicans ∆mnn4/∆bmt1 double deletant. Thin-layer chromatography and nuclear magnetic resonance analyses revealed that the deletant lacked β-1,2-mannosides in N-linked mannan. Mannans lacking the β-1,2-mannosides induced the production of higher levels of inflammatory cytokines, including IL-6, IL-12p40 and TNF-α, in mice dendritic cells compared to wild-type mannan. Our data show that β-1,2-mannosides in N-linked mannan reduce the production of inflammatory cytokines by dendritic cells.
mannan, cytokine, Candida albicans, β-1, 2-mannosides, BMDC
NCBI PubMed ID: 23101887Publication DOI: 10.3109/13693786.2012.733892Journal NLM ID: 9815835Publisher: Oxford: Oxford University Press
Correspondence: Kinjo Y
Institutions: Department of Chemistry, Graduate School of Science, Osaka City University, Osaka, Japan, Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo, Japan, Department of Bacteriology, Graduate School of Medicine, Osaka City University, Osaka, Japan, Department of Infectious Disease and Infection Control, Saitama Medical University, Saitama, Japan, Department of Oral Sciences and the Sir John Walsh Research Institute, University of Otago, Dunedin, New Zealand
Methods: 1H NMR, NMR-2D, TLC, ELISA, acid hydrolysis, extraction, cytokine assay, cell growth