title: Interferon-β production via Dectin-1-Syk-IRF5 signaling in dendritic cells is crucial for immunity to C. albicans.
abstract: Type I interferon (IFN) is crucial during infection through its antiviral properties and by coordinating the immunocompetent cells involved in antiviral or antibacterial immunity. Type I IFN (IFN-α and IFN-β) is produced after virus or bacteria recognition by cytosolic receptors or membrane-bound TLR receptors following the activation of the transcription factors IRF3 or IRF7. IFN-β production after fungal infection was recently reported, although the underlying mechanism remains controversial. Here we describe that IFN-β production by dendritic cells (DCs) induced by Candida albicans is largely dependent on Dectin-1- and Dectin-2-mediated signaling. Dectin-1-induced IFN-β production required the tyrosine kinase Syk and the transcription factor IRF5. Type I IFN receptor-deficient mice had a lower survival after C. albicans infection, paralleled by defective renal neutrophil infiltration. IFN-β production by renal infiltrating leukocytes was severely reduced in C. albicans-infected mice with Syk-deficient DCs. These data indicate that Dectin-induced IFN-β production by renal DCs is crucial for defense against C. albicans infection.
authors.affiliation: Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/CSIC, C/ Darwin 3, 28049 Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: del Fresno
authors.forename: Didier
authors.initials: D
authors.lastname: Soulat
authors.forename: Susanne
authors.initials: S
authors.lastname: Roth
authors.forename: Katrina
authors.initials: K
authors.lastname: Blazek
authors.forename: Irina
authors.initials: I
authors.lastname: Udalova
authors.forename: David
authors.initials: D
authors.lastname: Sancho
authors.forename: Jürgen
authors.initials: J
authors.lastname: Ruland
authors.forename: Carlos
authors.initials: C
authors.lastname: Ardavín
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology*; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology; D050835:Interferon Regulatory Factors / Q000378:metabolism; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000276:immunology; D037181:Lectins, C-Type / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D000072377:Syk Kinase; D000099181:Dectin-1
chemical_list: D050835:Interferon Regulatory Factors; D016899:Interferon-beta; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; D000099181:Dectin-1; C498178:Irf5 protein, mouse; C000606897:Syk protein, mouse