title: Novel structural features in Candida albicans hyphal glucan provide a basis for differential innate immune recognition of hyphae versus yeast.
abstract: The innate immune system differentially recognizes Candida albicans yeast and hyphae. It is not clear how the innate immune system effectively discriminates between yeast and hyphal forms of C. albicans. Glucans are major components of the fungal cell wall and key fungal pathogen-associated molecular patterns. C. albicans yeast glucan has been characterized; however, little is known about glucan structure in C. albicans hyphae. Using an extraction procedure that minimizes degradation of the native structure, we extracted glucans from C. albicans hyphal cell walls. (1)H NMR data analysis revealed that, when compared with reference (1→3,1→6) β-linked glucans and C. albicans yeast glucan, hyphal glucan has a unique cyclical or "closed chain" structure that is not found in yeast glucan. GC/MS analyses showed a high abundance of 3- and 6-linked glucose units when compared with yeast β-glucan. In addition to the expected (1→3), (1→6), and 3,6 linkages, we also identified a 2,3 linkage that has not been reported previously in C. albicans. Hyphal glucan induced robust immune responses in human peripheral blood mononuclear cells and macrophages via a Dectin-1-dependent mechanism. In contrast, C. albicans yeast glucan was a much less potent stimulus. We also demonstrated the capacity of C. albicans hyphal glucan, but not yeast glucan, to induce IL-1β processing and secretion. This finding provides important evidence for understanding the immune discrimination between colonization and invasion at the mucosal level. When taken together, these data provide a structural basis for differential innate immune recognition of C. albicans yeast versus hyphae.
authors.affiliation: From the Department of Surgery and.
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Lowman
authors.forename: Rachel R
authors.initials: RR
authors.lastname: Greene
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Bearden
authors.forename: Michael D
authors.initials: MD
authors.lastname: Kruppa
authors.forename: Max
authors.initials: M
authors.lastname: Pottier
authors.forename: Mario A
authors.initials: MA
authors.lastname: Monteiro
authors.forename: Dmitriy V
authors.initials: DV
authors.lastname: Soldatov
authors.forename: Harry E
authors.initials: HE
authors.lastname: Ensley
authors.forename: Shih-Chin
authors.initials: SC
authors.lastname: Cheng
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.forename: David L
authors.initials: DL
authors.lastname: Williams
mesh_terms: D002176:Candida albicans / Q000737:chemistry / Q000276:immunology*; D002236:Carbohydrate Conformation; D005260:Female; D062610:Fungal Polysaccharides / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D025301:Hyphae / Q000737:chemistry / Q000378:metabolism*; D007113:Immunity, Innate; D053583:Interleukin-1beta / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male
chemical_list: D062610:Fungal Polysaccharides; C508585:IL1B protein, human; D053583:Interleukin-1beta
keywords: Candida albicans; Carbohydrate Structure; Glucan; Host-Pathogen Interactions; Hyphae; Immune Function; Immunology; NMR