title: Nanoscopic cell-wall architecture of an immunogenic ligand in Candida albicans during antifungal drug treatment.
abstract: 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.
authors.affiliation: Center for Spatiotemporal Modeling of Cell Signaling, University of New Mexico, Albuquerque, NM 87131 Department of Pathology, University of New Mexico, Albuquerque, NM 87131.
authors.forename: Jia
authors.initials: J
authors.lastname: Lin
authors.affiliation: Center for Spatiotemporal Modeling of Cell Signaling, University of New Mexico, Albuquerque, NM 87131 Department of Mathematics and Statistics, University of New Mexico, Albuquerque, NM 87131.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Wester
authors.affiliation: Center for Spatiotemporal Modeling of Cell Signaling, University of New Mexico, Albuquerque, NM 87131 Department of Pathology, University of New Mexico, Albuquerque, NM 87131.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Graus
authors.affiliation: Center for Spatiotemporal Modeling of Cell Signaling, University of New Mexico, Albuquerque, NM 87131 Department of Physics and Astronomy, University of New Mexico, Albuquerque, NM 87131.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Lidke
authors.affiliation: Center for Spatiotemporal Modeling of Cell Signaling, University of New Mexico, Albuquerque, NM 87131 Department of Pathology, University of New Mexico, Albuquerque, NM 87131 akneumann@salud.unm.edu.
authors.forename: Aaron K
authors.initials: AK
authors.lastname: Neumann
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D002236:Carbohydrate Conformation; D000077336:Caspofungin; D002473:Cell Wall / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D003713:Dendritic Cells / Q000378:metabolism / Q000382:microbiology; D054714:Echinocandins / Q000494:pharmacology*; D006801:Humans; D037181:Lectins, C-Type; D008024:Ligands; D055666:Lipopeptides / Q000494:pharmacology*; D047071:beta-Glucans / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D000099181:Dectin-1
chemical_list: D000935:Antifungal Agents; D000077336:Caspofungin; D054714:Echinocandins; D037181:Lectins, C-Type; D008024:Ligands; D055666:Lipopeptides; D047071:beta-Glucans; D000099181:Dectin-1