A novel immunocompetent murine model for Candida albicans-promoted oral epithelial dysplasia

Candida albicans is a common opportunistic pathogen found in the oral mucosa. Clinical observations indicate a significant positive association between oral Candida carriage or infection and oral epithelial dysplasia/neoplasia. The aim of this study was to test whether C. albicans is able to promote epithelial dysplasia or carcinoma in a mouse model of infection where a carcinogen (4 Nitroquinoline 1-oxide [4NQO]) was used as initiator of neoplasia. Mice were divided into four groups: group 1 received 4NQO alone; group 2 received 4NQO followed by C. albicans (ATCC 90234); group 3 received vehicle dimethyl sulfoxide (DMSO) followed by C. albicans and group 4 was untreated. Although 4NQO treated mice did not develop oral lesions, mice exposed to both 4NQO and C. albicans developed oral dysplastic lesions 19 weeks after exposure to 4NQO. Mice challenged with C. albicans only developed hyperplastic lesions. The expression of Ki-67 and p16, two cell-cycle associated proteins that are frequently deregulated in oral dysplasia/neoplasia, was also tested in these lesions. Ki-67 and p16 expression increased from normal to hyperplastic to dysplastic mucosa and was highest in the group exposed to both 4NQO and C. albicans. In conclusion, we showed that C. albicans plays a role in the promotion of oral dysplasia in a mouse model of infection when 4NQO was used as initiator of oral neoplasia.