IL-36 and IL-1/IL-17 Drive Immunity to Oral Candidiasis via Parallel Mechanisms

• DOI: 10.4049/jimmunol.1800515
• Publication Date: 2018-06-11T15:40:08Z
• Authors: Akash H Verma; Hanna Zafar; Nicole O Ponde; Olivia W Hepworth; Diksha Sihra; Felix E Y Aggor; Joseph S Ainscough; Jemima Ho; Jonathan P Richar...; Bianca M Coleman; Bernhard Hube; Martin Stacey; Mandy J McGeachy; Julian R Naglik; Sarah L Gaffen; David L Moyes
• Keywords: Mice, Knockout; 0301 basic medicine; 0303 health sciences; Interleukin-17; Candidiasis; Mouth Mucosa; Receptors, Interleukin-1; Interleukin-23; p38 Mitogen-Activated Protein Kinases; Immunity, Innate; Cell Line; 3. Good health; Fungal Proteins; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Gene Expression Regulation; 616; Candida albicans; Animals; Adaptor Proteins, Signal Transducing; Interleukin-1; Signal Transduction

Protection against microbial infection by the induction of inflammation is a key function IL-1 superfamily, including both classical and new IL-36 cytokine families. Candida albicans frequent human fungal pathogen causing mucosal infections. Although initiators effectors important in protective host responses to C. are well described, players driving these remain poorly defined. Recent work has identified central role played inducing innate Type-17 immune clear Despite this, lack signaling does not result complete loss immunity, indicating that there other factors involved mediating protection this fungus. In study, we identify cytokines as player responses. We show oral mucosa induces production IL-36. As with IL-1α/β, epithelial depends on hypha-associated peptide toxin Candidalysin. Epithelial gene expression requires p38-MAPK/c-Fos, NF-κB, PI3K regulated MAPK phosphatase MKP1. Oral candidiasis IL-36R-/- mice shows increased burdens reduced IL-23 expression, Strikingly, observed no impact IL-17 or IL-17-dependent genes, occurs via an alternative pathway IL-1-driven immunity. Thus, represent parallel cell-driven pathways immunity infection.