Divergent EGFR/MAPK-Mediated Immune Responses to Clinical Pathogens in Vulvovaginal Candidiasis.

Vulvovaginal candidiasis (VVC) is characterized by symptomatic inflammatory responses in the vagina caused by and non-albicans (NAC) species. The epidermal growth factor receptor (EGFR) -mitogen-activated protein kinase (MAPK) signaling pathway has been linked to immune responses of oral mucosa after exposure, but whether this pathway plays a similar response in vaginal epithelial cells is not known. Here, we observed that phosphorylation of EGFR and p38 was continuously activated in vaginal epithelial cells by strain SC5314. This differs markedly from oral epithelial cells, which respond in a biphasic manner in order to properly discriminate the morphology of . When compared with SC5314, a highly azole-resistant isolate 1052 can induce a stronger phosphorylated signal of EGFR and p38, while clinically-isolated NAC strains including , , and trigger higher levels of phosphorylated ERK1/2 and c-Fos than . Inhibition of EGFR significantly reduces inflammatory response and epithelial damage induced by both and , while inhibition of p38 leads to significant repair of epithelial damage triggered by both and NAC species. These results confirm the importance of the EGFR-MAPK signaling in VVC pathogenesis and highlight the remarkable immunogenic differences between and NAC species in host-microbe interactions.