Normal Human Gingival Epithelial Cells SenseC. parapsilosisby Toll-Like Receptors and Module Its Pathogenesis through Antimicrobial Peptides and Proinflammatory Cytokines

Abstract

This study was designed to investigate the interaction betweenC. parapsilosisand human epithelial cells using monolayer cultures and an engineered human oral mucosa (EHOM).C. parapsilosiswas able to adhere to gingival epithelial cells and to adopt the hyphal form in the presence of serum. Interestingly, when cultured onto the engineered human oral mucosa (EHOM),C. parapsilosisformed small biofilm and invaded the connective tissue. Following contact withC. parapsilosis, normal human gingival epithelial cells expressed high levels of Toll-like receptors (TLR)-2, -4, and -6, but not TLR-9 mRNA. The upregulation of TLRs was paralleled by an increase of IL-1β, TNFα, and IFNγmRNA expression, suggesting the involvement of these cytokines in the defense against infection withC. parapsilosis. The active role of epithelial cells in the innate immunity againstC. parapsilosisinfection was enhanced by their capacity to express high levels of human beta-defensin-1, -2, and -3. The upregulation of proinflammatory cytokines and antimicrobial peptide expression may explain the growth inhibition ofC. parapsilosisby the gingival epithelial cells. Overall results provide additional evidence of the involvement of epithelial cells in the innate immunity againstC. parapsilosisinfections.