Fig 1.
(A) Overview of mechanistic IFN-I signaling, activating ISG expression via route of the IFNAR heterodimer and downstream interaction of the kinases JAK1 and TYK2 with STAT1/2 transcription factors. (B) Overview of how IFN-I steer immune responses in infections caused by Candida species and A. fumigatus. C. albicans causes specific enrichment of IFN-I responses, and genetic variations in the IFN-I pathway are linked to susceptibility to candidiasis and aspergillosis. While remaining controversial in systemic candidiasis, IFN-I are largely found protective on mucosae and during aspergillosis rather a protective role is observed. This renders IFN-I lucrative as potential immunotherapeutics on mucosal surfaces. CCL8, C-C motif chemokine ligand 8/monocyte chemoattractant protein 2; CGD, Chronic granulomatous disease; IBD, inflammatory bowel disease; IFN-I/I, type I interferon; III, type III interferon; IFNAR, IFN-α/β receptor; ISG, interferon-stimulated gene; JAK1, Janus kinase 1; MAVS, mitochondrial antiviral signaling protein; MDA5, melanoma differentiation-associated protein 5/interferon induced with helicase C domain 1; pDC, plasmacytoid dendritic cell; PSMB8, proteasome 20S subunit beta-8; SP110, speckled 110 kD/interferon-induced protein 41; STAT, signal transducer and activator of transcription; TLR, Toll-like receptor; TYK2, tyrosine kinase 2; VVC, vulvovaginal candidiasis.