Epithelial Innate Responses to Candida Albicans

Objectives: Host mechanisms enabling discrimination between commensal and pathogenic organisms are critical in mucosal immune defense and homeostasis. The polymorphic human fungal pathogen Candida albicans can act as a commensal or pathogen. Here we aim to determine now oral epithelial cells discriminate between the yeast (commensal) and hyphal (pathogenic) states of the fungal pathogen Candida albicans.

Methods: and Results: Oral epithelial cells orchestrate the innate response to this adaptable fungus via NF-kB and a biphasic MAPK response. Only hyphal forms of C. albicans activate the biphasic MAPK response, which constitutes MKP-1 phosphorylation, activation of the transcription factor c-Fos, and induction of a pro-inflammatory response that leads to a protective host phenotype. The yeast phase subverts the biphasic MAPK/MKP-1/c-Fos response resulting in the absence of inflammatory mediators, thus permitting the fungus to colonize mucosal surfaces without host challenge.

Conclusions: We propose a mechanism enabling epithelial cells to distinguish between commensal and pathogenic organisms through selective activation of MAPK signaling, MAPK phosphatases and transcription factors.