Candida albicans induces early apoptosis followed by secondary necrosis in oral epithelial cells.
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.
Department of Periodontics, The University of Texas, Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA. villar@uthscsa.edu
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D017209:Apoptosis; D002176:Candida albicans / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018920:Coculture Techniques; D053938:DNA Fragmentation; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000382:microbiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D020287:In Situ Nick-End Labeling; D009061:Mouth Mucosa / Q000166:cytology / Q000382:microbiology*; D009336:Necrosis; D010718:Phosphatidylserines / Q000378:metabolism
D010718:Phosphatidylserines; D020169:Caspases