Cytotoxic and cytokine-inducing properties of Candida glabrata in single and mixed oral infection models

Oral candidiasis is a common opportunistic infection, with Candida albicans being the most prevalent etiologic agent and Candida glabrata emerging as an important pathogen. C glabrata is frequently co-isolated with C albicans from oral lesions. Although C albicans has been shown to trigger significant cytokine responses and cell damage, C glabrata has not been systematically studied yet. The purpose of this study was to characterize the ability of C glabrata to induce proinflammatory cytokine responses and host damage as a single infecting organism and in combination with C albicans, using in vitro models of the oral mucosa. In monolayer oral epithelial cell cultures, C glabrata failed to induce a significant interleukin-1 alpha and interleukin-8 cytokine response and showed lower cytotoxicity, compared to C albicans. However, C glabrata triggered a significantly higher granulocyte macrophage colony stimulating factor response than C albicans. C glabrata strains showed a strain-dependent tissue damaging ability and a superficial invasion of the mucosal compartment in a three-dimensional (3-D) in vitro model of the human oral mucosa and submucosa. In the 3-D system, co-infection failed to promote host damage beyond the levels of infection with C albicans alone. These studies indicate that C glabrata induces cytokines in human oral epithelium in a strain-specific manner, but its tissue/cell damaging ability, compared to C albicans, is low. Synergy between C glabrata and C albicans in cytokine induction and host damage was not observed with the strains tested. (c) 2007 Elsevier Ltd. All rights reserved.