Nanoscopic cell-wall architecture of an immunogenic ligand in Candida albicans during antifungal drug treatment

The cell wall of Candida albicans is composed largely of polysaccharides. Here we focus on β-glucan, an immunogenic cell-wall polysaccharide whose surface exposure is often restricted, or "masked," from immune recognition by Dectin-1 on dendritic cells (DCs) and other innate immune cells....

Full description

Saved in:
Bibliographic Details
Published in:Molecular biology of the cell 2016-03, Vol.27 (6), p.1002-1014
Main Authors: Lin, Jia, Wester, Michael J, Graus, Matthew S, Lidke, Keith A, Neumann, Aaron K
Format: Article
Language:English
Subjects:
Antifungal Agents - pharmacology
beta-Glucans - chemistry
beta-Glucans - immunology
beta-Glucans - metabolism
Candida albicans - drug effects
Candida albicans - immunology
Candida albicans - metabolism
Carbohydrate Conformation
Cell Wall - drug effects
Cell Wall - metabolism
Cell Wall - ultrastructure
Dendritic Cells - metabolism
Dendritic Cells - microbiology
Echinocandins - pharmacology
Humans
Lectins, C-Type
Ligands
Lipopeptides - pharmacology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The cell wall of Candida albicans is composed largely of polysaccharides. Here we focus on β-glucan, an immunogenic cell-wall polysaccharide whose surface exposure is often restricted, or "masked," from immune recognition by Dectin-1 on dendritic cells (DCs) and other innate immune cells. Previous research suggested that the physical presentation geometry of β-glucan might determine whether it can be recognized by Dectin-1. We used direct stochastic optical reconstruction microscopy to explore the fine structure of β-glucan exposed on C. albicans cell walls before and after treatment with the antimycotic drug caspofungin, which alters glucan exposure. Most surface-accessible glucan on C. albicans yeast and hyphae is limited to isolated Dectin-1-binding sites. Caspofungin-induced unmasking caused approximately fourfold to sevenfold increase in total glucan exposure, accompanied by increased phagocytosis efficiency of DCs for unmasked yeasts. Nanoscopic imaging of caspofungin-unmasked C. albicans cell walls revealed that the increase in glucan exposure is due to increased density of glucan exposures and increased multiglucan exposure sizes. These findings reveal that glucan exhibits significant nanostructure, which is a previously unknown physical component of the host-Candida interaction that might change during antifungal chemotherapy and affect innate immune activation.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.E15-06-0355