{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:29:42Z","timestamp":1789010982815,"version":"build-2803163510"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T00:00:00Z","timestamp":1653523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Vulvovaginal candidiasis (VVC) is characterized by symptomatic inflammatory responses in the vagina caused by <jats:italic>Candida albicans<\/jats:italic> and non-albicans <jats:italic>Candida<\/jats:italic> (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 <jats:italic>C. albicans<\/jats:italic> 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 <jats:italic>C. albicans<\/jats:italic> strain SC5314. This differs markedly from oral epithelial cells, which respond in a biphasic manner in order to properly discriminate the morphology of <jats:italic>C. albicans<\/jats:italic>. When compared with SC5314, a highly azole-resistant <jats:italic>C. albicans<\/jats:italic> isolate 1052 can induce a stronger phosphorylated signal of EGFR and p38, while clinically-isolated NAC strains including <jats:italic>C. tropicalis<\/jats:italic>, <jats:italic>C. glabrata<\/jats:italic>, <jats:italic>C. parapsilosis<\/jats:italic> and <jats:italic>C. auris<\/jats:italic> trigger higher levels of phosphorylated ERK1\/2 and c-Fos than <jats:italic>C. albicans<\/jats:italic>. Inhibition of EGFR significantly reduces inflammatory response and epithelial damage induced by <jats:italic>C. albicans<\/jats:italic> both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>, while inhibition of p38 leads to significant repair of epithelial damage triggered by both <jats:italic>C. albicans<\/jats:italic> and NAC species. These results confirm the importance of the EGFR-MAPK signaling in VVC pathogenesis and highlight the remarkable immunogenic differences between <jats:italic>C. albicans<\/jats:italic> and NAC species in host-microbe interactions.<\/jats:p>","DOI":"10.3389\/fimmu.2022.894069","type":"journal-article","created":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T11:13:07Z","timestamp":1654254787000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Divergent EGFR\/MAPK-Mediated Immune Responses to Clinical Candida Pathogens in Vulvovaginal 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