| First Author | Taylor TC | Year | 2023 |
| Journal | Cell Host Microbe | Volume | 31 |
| Issue | 10 | Pages | 1700-1713.e4 |
| PubMed ID | 37725983 | Mgi Jnum | J:341717 |
| Mgi Id | MGI:7540263 | Doi | 10.1016/j.chom.2023.08.016 |
| Citation | Taylor TC, et al. (2023) IkappaBzeta is an essential mediator of immunity to oropharyngeal candidiasis. Cell Host Microbe 31(10):1700-1713.e4 |
| abstractText | 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, IkappaBzeta (Nfkbiz, a non-canonical NF-kappaB 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. IkappaBzeta was dispensable in hematopoietic cells and acted partially in the suprabasal oral epithelium to control OPC. One prominent IkappaBzeta-dependent gene target was beta-defensin 3 (BD3) (Defb3), an essential antimicrobial peptide. Human oral epithelial cells required IkappaBzeta for IL-17-mediated induction of BD2 (DEFB4A, human ortholog of mouse Defb3) through binding to the DEFB4A promoter. Unexpectedly, IkappaBzeta regulated the transcription factor Egr3, which was essential for C. albicans induction of BD2/DEFB4A. Accordingly, IkappaBzeta and Egr3 comprise an antifungal signaling hub mediating mucosal defense against oral candidiasis. |
