Innate immune signaling molecules regulate the Candida and epithelial cross-talk

Abstract

Objective: Cross-talk between host epithelial cells and Candida results in either passive coexistence as a commensal or transformation of the fungi into a pathogenic form. Therefore, objective of the present study was to investigate the innate immune signaling molecules that regulate the cross-talk between Candida and epithelial cells. Methods: Primary human oral keratinocytes and well characterized C. albicans wild type SC5314 (WT) and its hyphal mutants MAPK (D cph1/cph), PKA (Defg1/efg1), MAPK/PKA (DDefg1/efg1 cph1/cph1) and SAP mutants (Dsap1-3 and Dsap4-6) were used. Interaction of Candida and epithelial keratinocytes was studied in a dose- and time-dependent experiments. Cellular viability was determined by fluorescent staining using confocal microscopy. Expression of toll-like receptors, signal transduction pathway molecules, cytokines, chemokines and antimicrobial peptides was evaluated by Q-PCR and ELISA. Results: C. albicans WT and D cph1/cph, D sap1-3 and D sap4-6 infected oral epithelial cells in dose- and time- dependent manner, whilst hyphal mutants D efg1/efg1 and DD efg1/efg1 cph1/cph1 were unable to infect the epithelial cells. Compared to the control, WT and MAPK mutant significantly upregulated the expression of IL-1alpha, IL-6 and IL-8, whereas PKA pathway mutants showed lack of expression. Expression of antimicrobial peptides hBDs and RNAse 7 were inhibited by WT and MAPK mutants, but not the PKA mutant. IL-1alpha, IL-6, IL-8, TNF-alpha were increased in a time-dependent manner. Conclusion: Innate immune response of oral epithelial cells governs pathogenic transformation of commensal Candida in PKA pathway dependent mechanism (HKU grants No200807176142 for LQ and RGCNoHKU 7624/06M to LP).