RRC ID 76908
Author Taylor TC, Coleman BM, Arunkumar SP, Dey I, Dillon JT, Ponde NO, Poholek AC, Schwartz DM, McGeachy MJ, Conti HR, Gaffen SL.
Title IκBζ is an essential mediator of immunity to oropharyngeal candidiasis.
Journal Cell Host Microbe
Abstract Fungal infections are a global threat; yet, there are no licensed vaccines to any fungal pathogens. Th17 cells mediate immunity to Candida albicans, particularly oropharyngeal candidiasis (OPC), but essential downstream mechanisms remain unclear. In the murine model of OPC, IκBζ (Nfkbiz, a non-canonical NF-κB transcription factor) was upregulated in an interleukin (IL)-17-dependent manner and was essential to prevent candidiasis. Deletion of Nfkbiz rendered mice highly susceptible to OPC. IκBζ was dispensable in hematopoietic cells and acted partially in the suprabasal oral epithelium to control OPC. One prominent IκBζ-dependent gene target was β-defensin 3 (BD3) (Defb3), an essential antimicrobial peptide. Human oral epithelial cells required IκBζ for IL-17-mediated induction of BD2 (DEFB4A, human ortholog of mouse Defb3) through binding to the DEFB4A promoter. Unexpectedly, IκBζ regulated the transcription factor Egr3, which was essential for C. albicans induction of BD2/DEFB4A. Accordingly, IκBζ and Egr3 comprise an antifungal signaling hub mediating mucosal defense against oral candidiasis.
Published 2023-9-11
DOI 10.1016/j.chom.2023.08.016
PII S1931-3128(23)00341-4
PMID 37725983
IF 15.923
Mice RBRC06410