Candida albicans induces early apoptosis followed by secondary necrosis in oral epithelial cells

Abstract

The capacity of Candida albicans to invade and damage oral epithelial cells is critical for its ability to establish and maintain symptomatic oropharyngeal infection. Although oral epithelial cells are reported dead after 18 h of candidal infection, activation of specific epithelial cell-death pathways in response to C. albicans infection has not yet been demonstrated. Considering the key role of oral epithelial cell damage in the pathogenesis of oropharyngeal candidiasis, the aim of this study was to characterize this event during infection. Using an oral epithelial-C. albicans co-culture system, we examined the ability of C. albicans to induce classic necrotic, pyroptotic and apoptotic cellular alterations in oral epithelial cells such as osmotic lysis, exposure of phosphatidylserine on the epithelial cell plasma membrane and internucleosomal DNA fragmentation. It was found that the ability of C. albicans to kill oral epithelial cells depends on its capacity to physically interact with and invade these cells. Caspase-dependent apoptotic pathways were activated early during C. albicans infection and contributed to C. albicans-induced oral epithelial cell death. Earlier apoptotic events were followed by necrotic death of infected oral epithelial cells. Hence, C. albicans stimulates oral epithelial signaling pathways that promote early apoptotic cell death through the activation of cellular caspases, followed by late necrosis.

Evaluation of tissue engineered models of the oral mucosa to investigate oral candidiasis

“…Epithelial cell damage in all models included desquamation of the upper epithelial layers and marked cellular damage, which was associated with a time-dependent increase in LDH release. Such findings are consistent with clinical observations of mucosal Candidal infections [32] and previous studies using mucosal models [33].…”

Synergistic Interaction between Candida albicans and Commensal Oral Streptococci in a Novel In Vitro Mucosal Model

“…Candida biofilms triggered a low level of apoptosis in the oral mucosa model which was not significantly increased by the addition of oral streptococci. The low levels of Candida-triggered oral epithelial cell apoptosis are consistent with previous reports in nonbiofilm systems (60). Although farnesol has been reported to trigger mammalian cell apoptosis (62), it is possible that it did not reach the concentration needed to enhance apoptotic cell death in our open flow system.…”

Candida albicans-epithelial interactions and pathogenicity mechanisms: scratching the surface

“…occurring within the first 4 hours after initial contact 57 and involves actin and other proteins associated with clathrin-mediated endocytosis (CME). 50 Another potential mechanism, involving the small GTPases Cdc42, Rac1 and RhoA, and ZO-1 (Zonula Occludens) has also been identified, 58 although at this time, it is unclear whether this mechanism is involved in endocytosis of fungal cells or shed/secreted fungal molecules.…”