Interferon-β Production via Dectin-1-Syk-IRF5 Signaling in Dendritic Cells Is Crucial for Immunity to C. albicans

• Published in: Immunity (Cambridge, Mass.) Vol. 38; no. 6; pp. 1176 - 1186
• Main Authors: del Fresno, Carlos, Soulat, Didier, Roth, Susanne, Blazek, Katrina, Udalova, Irina, Sancho, David, Ruland, Jürgen, Ardavín, Carlos
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 27.06.2013
• Subjects: Animals; Candida albicans; Candida albicans - immunology; Candidiasis - immunology; Cell Movement - genetics; Cells, Cultured; Dendritic Cells - immunology; Dendritic Cells - microbiology; Interferon Regulatory Factors - metabolism; Interferon-beta - genetics; Interferon-beta - metabolism; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Kidney - immunology; Lectins, C-Type - metabolism; Mice; Mice, Knockout; Neutrophils - immunology; Protein-Tyrosine Kinases - genetics; Protein-Tyrosine Kinases - metabolism; Signal Transduction - genetics; Syk Kinase
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2013.05.010

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. [Display omitted] •IFN-β production in response to Candida is mainly controlled by Dectin-1 signaling•Dectin-1 triggers IFN-β production by a Syk-Card9-IRF5-dependent pathway•IFNAR deficiency reduces renal neutrophil influx and survival after Candida infection•Renal IFN-β production during Candida infection mainly relies on DCs and Syk signaling