title: Glycosylation of Candida albicans cell wall proteins is critical for induction of innate immune responses and apoptosis of epithelial cells.
abstract: C. albicans is one of the most common fungal pathogen of humans, causing local and superficial mucosal infections in immunocompromised individuals. Given that the key structure mediating host-C. albicans interactions is the fungal cell wall, we aimed to identify features of the cell wall inducing epithelial responses and be associated with fungal pathogenesis. We demonstrate here the importance of cell wall protein glycosylation in epithelial immune activation with a predominant role for the highly branched N-glycosylation residues. Moreover, these glycan moieties induce growth arrest and apoptosis of epithelial cells. Using an in vitro model of oral candidosis we demonstrate, that apoptosis induction by C. albicans wild-type occurs in early stage of infection and strongly depends on intact cell wall protein glycosylation. These novel findings demonstrate that glycosylation of the C. albicans cell wall proteins appears essential for modulation of epithelial immunity and apoptosis induction, both of which may promote fungal pathogenesis in vivo.
authors.affiliation: Department of Dermatology, Eberhard Karls University Tübingen, Tübingen, Germany.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Wagener
authors.forename: Günther
authors.initials: G
authors.lastname: Weindl
authors.forename: Piet W J
authors.initials: PW
authors.lastname: de Groot
authors.forename: Albert D
authors.initials: AD
authors.lastname: de Boer
authors.forename: Susanne
authors.initials: S
authors.lastname: Kaesler
authors.forename: Selvam
authors.initials: S
authors.lastname: Thavaraj
authors.forename: Oliver
authors.initials: O
authors.lastname: Bader
authors.forename: Daniela
authors.initials: D
authors.lastname: Mailänder-Sanchez
authors.forename: Claudia
authors.initials: C
authors.lastname: Borelli
authors.forename: Michael
authors.initials: M
authors.lastname: Weig
authors.forename: Tilo
authors.initials: T
authors.lastname: Biedermann
authors.forename: Julian R
authors.initials: JR
authors.lastname: Naglik
authors.forename: Hans Christian
authors.initials: HC
authors.lastname: Korting
authors.forename: Martin
authors.initials: M
authors.lastname: Schaller
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D002176:Candida albicans / Q000166:cytology* / Q000502:physiology; D059447:Cell Cycle Checkpoints / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002473:Cell Wall / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology* / Q000276:immunology / Q000382:microbiology*; D005656:Fungal Proteins / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology; D006031:Glycosylation; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D008810:Mice, Inbred C57BL; D011134:Polysaccharides / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D016207:Cytokines; D005656:Fungal Proteins; D011134:Polysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4