Cytokine and chemokine production by human oral and vaginal epithelial cells in response to Candida albicans

Abstract

Oropharyngeal and vaginal candidiases are the most common forms of mucosal fungal infections and are primarily caused by Candida albicans, a dimorphic fungal commensal organism of the gastrointestinal and lower female reproductive tracts. Clinical and experimental observations suggest that local immunity is important in host defense against candidiasis. Accordingly, cytokines and chemokines are present at the oral and vaginal mucosa during C. albicans infections. Since mucosal epithelial cells produce a variety of cytokines and chemokines in response to microorganisms and since C. albicans is closely associated with mucosal epithelial cells as a commensal, we sought to identify cytokines and/or chemokines produced by primary oral and vaginal epithelial cells and cell lines in response to C. albicans. The results showed that proinflammatory cytokines were produced by oral and/or vaginal epithelial cells at various levels constitutively with considerable interleukin-1alpha (IL-1alpha) and tumor necrosis factor alpha, but not IL-6, produced in response to C. albicans. In contrast, Th1-type (IL-12 and gamma interferon) and Th2-type-immunoregulatory (IL-10 and transforming growth factor beta) cytokines and the chemokines monocyte chemoattractant protein 1 and IL-8 were produced in low to undetectable concentrations with little additional production in response to C. albicans. Taken together, these results indicate that cytokines and chemokines are variably produced by oral and vaginal epithelial cells constitutively, as well as in response to C. albicans, and are predominated by proinflammatory cytokines.

FIG. 1.

TNF-α production by oral and vaginal epithelial cells in response to C. albicans. Whole unstimulated saliva and vaginal lavage fluid were collected from healthy human volunteers, and epithelial cell-enriched populations were isolated through nylon membrane retention. Primary oral (A) and vaginal (B) epithelial cells and oral/cervical and vaginal epithelial line cells (C) were cocultured with C. albicans at an epithelial cell/Candida ratio of 1:100 for up to 96 h. Supernatants of the Candida-epithelial cell coculture were collected at specified time points, and TNF-α levels were quantified by ELISA. The figure shows the mean concentrations of Candida-specific (minus the concentrations in medium alone) production of TNF-α from five volunteers examined individually and four separate experiments with each epithelial cell line.

FIG. 2.

IL-1α production by oral and vaginal epithelial cells in response to C. albicans. Whole unstimulated saliva and vaginal lavage fluid were collected from healthy human volunteers, and epithelial cell-enriched populations were isolated through nylon membrane retention. Primary oral (A) and vaginal (B) epithelial cells and oral/cervical and vaginal epithelial line cells (C) were cocultured with C. albicans at an epithelial cell/Candida ratio of 1:100 for up to 96 h. Supernatants of the Candida-epithelial cell coculture were collected at specific time points, and IL-1α levels were quantified by ELISA. The figure shows the mean concentrations of Candida-specific (minus the concentrations in medium alone) production of IL-1α from five volunteers examined individually and four separate experiments with each epithelial cell line.

FIG. 3.

MCP-1 production by oral and vaginal epithelial cells in response to C. albicans. Whole unstimulated saliva and vaginal lavage fluid were collected from healthy human volunteers, and epithelial cell-enriched populations were isolated through nylon membrane retention. Primary oral (A) and vaginal (B) epithelial cells and oral/cervical and vaginal epithelial line cells (C) were cocultured with C. albicans at an epithelial cell/Candida ratio of 1:100 for up to 96 h. Supernatants of the Candida-epithelial cell coculture were collected at specific time points, and MCP-1 levels were quantified by ELISA. The figure shows the mean concentrations of Candida-specific (minus the concentrations in medium alone) production of MCP-1 from five volunteers examined individually and four separate experiments with each epithelial cell line.