Potential role for a carbohydrate moiety in anti-Candida activity of humanoral epithelial cells

Candida albicans is both a commensal and a pathogen at the oral mucosa. Alt hough an intricate network of host defense mechanisms are expected for prot ection against oropharyngeal candidiasis, anti-Candida host defense mechani sms at the oral mucosa are poorly understood. Our laboratory recently showe d that primary epithelial cells from human oral mucosa, as well as an oral epithelial cell line, inhibit the growth of blastoconidia. and/or hyphal ph ases of several Candida species in vitro with a requirement for cell contac t and with no demonstrable role for soluble factors. In the present study, we show that oral epithelial cell-mediated anti-Candida activity is resista nt to gamma-irradiation and is not mediated by phagocytosis, nitric oxide, hydrogen peroxide, and superoxide oxidative inhibitory pathways or by nonox idative components such as soluble defensin and calprotectin peptides. In c ontrast, epithelial cell-mediated anti-Candida activity was sensitive to he at, paraformaldehyde fixation, and detergents, but these treatments were ac companied by a significant loss in epithelial cell viability. Treatments th at removed existing membrane protein or lipid moieties in the presence or a bsence of protein synthesis inhibitors had no effect on epithelial cell inh ibitory activity. In contrast, the epithelial cell-mediated anti-Candida ac tivity was abrogated after treatment of the epithelial cells with periodic acid, suggesting a role for carbohydrates. Adherence of C albicans to oral epithelial cells was unaffected, indicating that the carbohydrate moiety is exclusively associated with the growth inhibition activity. Subsequent stu dies that evaluated specific membrane carbohydrate moieties, however, showe d no role for sulfated polysaccharides, sialic acid residues, or glucose- a nd mannose-containing carbohydrates. These results suggest that oral epithe lial cell-mediated anti-Candida activity occurs exclusively with viable epi thelial cells through contact with C albicans by an as-yet-undefined carboh ydrate moiety.