Surface Glycans ofCandida albicansand Other Pathogenic Fungi: Physiological Roles, Clinical Uses, and Experimental Challenges

Abstract

Although fungi have always been with us as commensals and pathogens, fungal infections have been increasing in frequency over the past few decades. There is a growing body of literature describing the involvement of carbohydrate groups in various aspects of fungal disease. Carbohydrates comprising the cell wall or capsule, or as a component of glycoproteins, are the fungal cell surface entities most likely to be exposed to the surrounding environment. Thus, the fungus-host interaction is likely to involve carbohydrates before DNA, RNA, or even protein. The interaction between fungal and host cells is also complex, and early studies using whole cells or crude cell fractions often produced seemingly conflicting results. What was needed, and what has been developing, is the ability to identify specific glycan structures and determine how they interact with immune system components. Carbohydrate analysis is complicated by the complexity of glycan structures and by the challenges of separating and detecting carbohydrates experimentally. Advances in carbohydrate chemistry have enabled us to move from the foundation of composition analysis to more rapid characterization of specific structures. This, in turn, will lead to a greater understanding of how fungi coexist with their hosts as commensals or exist in conflict as pathogens

Dendritic Cell Interaction with Candida albicans Critically Depends on N-Linked Mannan

“…Stimulation of IL-6 Production in Human DCs-Samples of 3 ϫ 10 5 immature DCs in 300-l volume were added to roundbottomed 48-well plates (Greiner Bio-One) and incubated with the various strains of C. albicans (ratio DCs/Candida ϭ 1:10). After incubation for 6 h at 37°C, the DCs/ C. albicans cell suspensions were centrifuged, and the supernatants were collected and stored at Ϫ70°C until assayed.…”

“…DC-SIGN Specifically Interacts with Candida-derived Mannan-The Candida cell wall is primarily comprised of mannan and by a lesser content of glucan and chitin (5). DC-SIGN is known to bind high mannose moieties (47).…”

Lectin mapping reveals stage-specific display of surface carbohydrates in in vitro and haemolymph-derived cells of the entomopathogenic fungus Beauveria bassiana

“…Lectins represent relatively simple probes for the identification of specific carbohydrate residues on the surfaces of cells, and have been extensively used to characterize fungal cell walls, including particularly the examination of host-pathogen interactions (Lis & Sharon, 1986;Sharon & Lis, 1993;Sharon, 2007). Differences in surface constituents during fungal growth and among various developmental stages may influence host-parasite interactions, and alternations in surface mannose, glucose and sialic acid epitopes in Candida albicans and Aspergillus fumigatus have been linked to their ability to infect and colonize hosts as well as to activate immune cells and cytokine production (Esquenazi et al, 2003;Latgé et al, 1994;Masuoka, 2004;Warwas et al, 2007).…”

Enhanced Immunogenicity of a Tricomponent Mannan Tetanus Toxoid Conjugate Vaccine Targeted to Dendritic Cells via Dectin-1 by Incorporating β-Glucan

“…Dectin-1 is a pattern-recognition receptor that has been implicated in defending against invasions by C. albicans (18)(19)(20), Aspergillus (21), Coccidioides (22), and Pneumocystis (23). This receptor is a single transmembrane protein with a carbohydrate recognition domain in its extracellular region that binds b-1,3-glucan (a major component of the cell wall of a variety of fungal pathogens), a transmembrane segment, and an N terminus cytosolic domain.…”