Details

Autor(en) / Beteiligte

• Taylor, Tiffany C.
• Coleman, Bianca M.
• Arunkumar, Samyuktha P.
• Dey, Ipsita
• Dillon, John T.
• Ponde, Nicole O.
• Poholek, Amanda C.
• Schwartz, Daniella M.
• McGeachy, Mandy J.
• Conti, Heather R.
• Gaffen, Sarah L.

Titel

IκBζ is an essential mediator of immunity to oropharyngeal candidiasis

Ist Teil von

• Cell host & microbe, 2023-10, Vol.31 (10), p.1700-1713.e4

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •During candidiasis, IκBζ (Nfkbiz) is upregulated in the oral mucosa via IL-17•Deletion of Nfkbiz renders mice highly susceptible to oropharyngeal candidiasis•IκBζ acts partially in the suprabasal oral epithelium•IκBζ and EGR3 regulate β-defensins, non-redundant antifungal effectors Fungal pathogens are of increasing medical concern. Oropharyngeal candidiasis (OPC) is the most common fungal infection in humans, but tissue-specific correlates of oral immunity are poorly understood. Taylor et al. show that IL-17 prevents OPC through the non-canonical transcription factor, IκBζ, which regulates essential antimicrobial peptide effectors.