Abstract
We demonstrated the effect of a Candida albicans sphingolipid biosynthetic gene, IPT1, on the interaction between gingival epithelial and Candida cells using monolayer cultures and engineered human oral mucosa tissue (EHOM). Disrupting the IPT1 gene greatly reduced Candida adhesion to gingival epithelial cells, compared to the wild-type and revertant strains. The yeasts adhesion to epithelial cells may activate toll-like receptors (TLRs). Cell response against Candida infection was thus investigated by evaluating TLR expression and antimicrobial peptide (AMP) production. The wild-type and revertant strains both activated TLR2, TLR4, TLR6, and TLR9 gene expression in the epithelial cells, whereas the Δipt1 mutant Candida strain had no effect on this expression. This finding was supported by an increased AMP expression (human β-defensin HBD-2 and HBD-3) in the EHOM tissue infected with the wild-type and revertant Candida strains, and a decreased expression in the Δipt1 mutant-infected model. HBD protein secretion confirmed the absence of any effect by the Δipt1 on epithelial cell innate defense. This is the first study to demonstrate that a disruption of the IPT1 gene affects Candida-host interaction, thus preventing TLR activation and β-defensin expression.
Acknowledgments
This study was supported by grants from the NIH/R01-DE017486-01A1 and BRS-ACURE Q0600136 (Oral HIV/AIDS Research Alliance, OHARA (MAG), NIH/NIAID, R21-AI74077-01 (PKM) and the Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Program (MR).
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
This paper was first Published online on Early Online on 24 November 2010.