title: Immune sensing of Candida albicans requires cooperative recognition of mannans and glucans by lectin and Toll-like receptors.
abstract: The fungal pathogen Candida albicans has a multilayered cell wall composed of an outer layer of proteins glycosylated with N- or O-linked mannosyl residues and an inner skeletal layer of beta-glucans and chitin. We demonstrate that cytokine production by human mononuclear cells or murine macrophages was markedly reduced when stimulated by C. albicans mutants defective in mannosylation. Recognition of mannosyl residues was mediated by mannose receptor binding to N-linked mannosyl residues and by TLR4 binding to O-linked mannosyl residues. Residual cytokine production was mediated by recognition of beta-glucan by the dectin-1/TLR2 receptor complex. C. albicans mutants with a cell wall defective in mannosyl residues were less virulent in experimental disseminated candidiasis and elicited reduced cytokine production in vivo. We concluded that recognition of C. albicans by monocytes/macrophages is mediated by 3 recognition systems of differing importance, each of which senses specific layers of the C. albicans cell wall.
authors.affiliation: Department of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. m.netea@aig.umcn.nl
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.forename: Neil A R
authors.initials: NA
authors.lastname: Gow
authors.forename: Carol A
authors.initials: CA
authors.lastname: Munro
authors.forename: Steven
authors.initials: S
authors.lastname: Bates
authors.forename: Claire
authors.initials: C
authors.lastname: Collins
authors.forename: Gerben
authors.initials: G
authors.lastname: Ferwerda
authors.forename: Richard P
authors.initials: RP
authors.lastname: Hobson
authors.forename: Gwyneth
authors.initials: G
authors.lastname: Bertram
authors.forename: H Bleddyn
authors.initials: HB
authors.lastname: Hughes
authors.forename: Trees
authors.initials: T
authors.lastname: Jansen
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Jacobs
authors.forename: Ed T
authors.initials: ET
authors.lastname: Buurman
authors.forename: Karlijn
authors.initials: K
authors.lastname: Gijzen
authors.forename: David L
authors.initials: DL
authors.lastname: Williams
authors.forename: Ruurd
authors.initials: R
authors.lastname: Torensma
authors.forename: Alistair
authors.initials: A
authors.lastname: McKinnon
authors.forename: Donna M
authors.initials: DM
authors.lastname: MacCallum
authors.forename: Frank C
authors.initials: FC
authors.lastname: Odds
authors.forename: Jos W M
authors.initials: JW
authors.lastname: Van der Meer
authors.forename: Alistair J P
authors.initials: AJ
authors.lastname: Brown
authors.forename: Bart Jan
authors.initials: BJ
authors.lastname: Kullberg
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000235:genetics / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002473:Cell Wall / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D016207:Cytokines / Q000276:immunology; D005936:Glucans / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008351:Mannans / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011975:Receptors, Mitogen / Q000737:chemistry / Q000276:immunology*; D051193:Toll-Like Receptors / Q000737:chemistry / Q000276:immunology*
chemical_list: D016207:Cytokines; D005936:Glucans; D008351:Mannans; D011975:Receptors, Mitogen; D051193:Toll-Like Receptors