AUTHOR=Zhang Jingyun , Peng Jingwen , Li Dongmei , Mei Huan , Yu Yu , Li Xiaofang , She Xiaodong , Liu Weida 

TITLE=Divergent EGFR/MAPK-Mediated Immune Responses to Clinical Candida Pathogens in Vulvovaginal Candidiasis

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.894069

DOI=10.3389/fimmu.2022.894069

ISSN=1664-3224

ABSTRACT=<p>Vulvovaginal candidiasis (VVC) is characterized by symptomatic inflammatory responses in the vagina caused by <italic>Candida albicans</italic> and non-albicans <italic>Candida</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 <italic>C. albicans</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 <italic>C. albicans</italic> strain SC5314. This differs markedly from oral epithelial cells, which respond in a biphasic manner in order to properly discriminate the morphology of <italic>C. albicans</italic>. When compared with SC5314, a highly azole-resistant <italic>C. albicans</italic> isolate 1052 can induce a stronger phosphorylated signal of EGFR and p38, while clinically-isolated NAC strains including <italic>C. tropicalis</italic>, <italic>C. glabrata</italic>, <italic>C. parapsilosis</italic> and <italic>C. auris</italic> trigger higher levels of phosphorylated ERK1/2 and c-Fos than <italic>C. albicans</italic>. Inhibition of EGFR significantly reduces inflammatory response and epithelial damage induced by <italic>C. albicans</italic> both <italic>in vitro</italic> and <italic>in vivo</italic>, while inhibition of p38 leads to significant repair of epithelial damage triggered by both <italic>C. albicans</italic> and NAC species. These results confirm the importance of the EGFR-MAPK signaling in VVC pathogenesis and highlight the remarkable immunogenic differences between <italic>C. albicans</italic> and NAC species in host-microbe interactions.</p>