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

• 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

SummaryType 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.

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