title: Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans.
abstract: Candida albicans is the most common human fungal pathogen causing mucosal and systemic infections. However, human antifungal immunity remains poorly defined. Here by integrating transcriptional analysis and functional genomics, we identified Candida-specific host defence mechanisms in humans. Candida induced significant expression of genes from the type I interferon pathway in human peripheral blood mononuclear cells. This unexpectedly prominent role of type I interferon pathway in anti-Candida host defence was supported by additional evidence. Polymorphisms in type I interferon genes modulated Candida-induced cytokine production and were correlated with susceptibility to systemic candidiasis. In in vitro experiments, type I interferons skewed Candida-induced inflammation from a Th17 response towards a Th1 response. Patients with chronic mucocutaneous candidiasis displayed defective expression of genes in the type I interferon pathway. These findings indicate that the type I interferon pathway is a main signature of Candida-induced inflammation and has a crucial role in anti-Candida host defence in humans.
authors.affiliation: Department of Medicine (463), Radboud University Nijmegen Medical Centre, Geert Grooteplein Zuid 8, 6525GA Nijmegen, The Netherlands.
authors.forename: Sanne P
authors.initials: SP
authors.lastname: Smeekens
authors.forename: Aylwin
authors.initials: A
authors.lastname: Ng
authors.forename: Vinod
authors.initials: V
authors.lastname: Kumar
authors.forename: Melissa D
authors.initials: MD
authors.lastname: Johnson
authors.forename: Theo S
authors.initials: TS
authors.lastname: Plantinga
authors.forename: Cleo
authors.initials: C
authors.lastname: van Diemen
authors.forename: Peer
authors.initials: P
authors.lastname: Arts
authors.forename: Eugène T P
authors.initials: ET
authors.lastname: Verwiel
authors.forename: Mark S
authors.initials: MS
authors.lastname: Gresnigt
authors.forename: Karin
authors.initials: K
authors.lastname: Fransen
authors.forename: Suzanne
authors.initials: S
authors.lastname: van Sommeren
authors.forename: Marije
authors.initials: M
authors.lastname: Oosting
authors.forename: Shih-Chin
authors.initials: SC
authors.lastname: Cheng
authors.forename: Leo A B
authors.initials: LA
authors.lastname: Joosten
authors.forename: Alexander
authors.initials: A
authors.lastname: Hoischen
authors.forename: Bart-Jan
authors.initials: BJ
authors.lastname: Kullberg
authors.forename: William K
authors.initials: WK
authors.lastname: Scott
authors.forename: John R
authors.initials: JR
authors.lastname: Perfect
authors.forename: Jos W M
authors.initials: JW
authors.lastname: van der Meer
authors.forename: Cisca
authors.initials: C
authors.lastname: Wijmenga
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.forename: Ramnik J
authors.initials: RJ
authors.lastname: Xavier
mesh_terms: D002176:Candida albicans / Q000276:immunology*; D058387:Candidemia / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D002178:Candidiasis, Chronic Mucocutaneous / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D016022:Case-Control Studies; D016000:Cluster Analysis; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D023281:Genomics; D054884:Host-Pathogen Interactions / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007370:Interferon Type I / Q000235:genetics* / Q000276:immunology*; D009154:Mutation / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D050794:STAT1 Transcription Factor / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics* / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D014158:Transcription, Genetic
chemical_list: D007370:Interferon Type I; D050794:STAT1 Transcription Factor