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Divergent EGFR/MAPK-Mediated Immune Responses to Clinical Candida Pathogens in Vulvovaginal Candidiasis.
Front Immunol. 2022; 13:894069.FI

Abstract

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

Authors+Show Affiliations

Department of Medical Mycology, Institute of Dermatology, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Nanjing, China. Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, China.Department of Medical Mycology, Institute of Dermatology, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Nanjing, China. Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, China.Department of Microbiology & Immunology, Georgetown University Medical Center, Washington, DC, United States.Department of Medical Mycology, Institute of Dermatology, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Nanjing, China. Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, China.Department of Medical Mycology, Institute of Dermatology, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Nanjing, China. Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, China.Department of Medical Mycology, Institute of Dermatology, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Nanjing, China. Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, China.Department of Medical Mycology, Institute of Dermatology, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Nanjing, China. Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, China.Department of Medical Mycology, Institute of Dermatology, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Nanjing, China. Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, China. Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

35720274

Citation

Zhang, Jingyun, et al. "Divergent EGFR/MAPK-Mediated Immune Responses to Clinical Candida Pathogens in Vulvovaginal Candidiasis." Frontiers in Immunology, vol. 13, 2022, p. 894069.
Zhang J, Peng J, Li D, et al. Divergent EGFR/MAPK-Mediated Immune Responses to Clinical Candida Pathogens in Vulvovaginal Candidiasis. Front Immunol. 2022;13:894069.
Zhang, J., Peng, J., Li, D., Mei, H., Yu, Y., Li, X., She, X., & Liu, W. (2022). Divergent EGFR/MAPK-Mediated Immune Responses to Clinical Candida Pathogens in Vulvovaginal Candidiasis. Frontiers in Immunology, 13, 894069. https://doi.org/10.3389/fimmu.2022.894069
Zhang J, et al. Divergent EGFR/MAPK-Mediated Immune Responses to Clinical Candida Pathogens in Vulvovaginal Candidiasis. Front Immunol. 2022;13:894069. PubMed PMID: 35720274.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Divergent EGFR/MAPK-Mediated Immune Responses to Clinical Candida Pathogens in Vulvovaginal Candidiasis. AU - Zhang,Jingyun, AU - Peng,Jingwen, AU - Li,Dongmei, AU - Mei,Huan, AU - Yu,Yu, AU - Li,Xiaofang, AU - She,Xiaodong, AU - Liu,Weida, Y1 - 2022/05/26/ PY - 2022/3/11/received PY - 2022/4/25/accepted PY - 2022/6/20/entrez PY - 2022/6/21/pubmed PY - 2022/6/22/medline KW - Candida albicans KW - EGFR KW - MAPK KW - non-albicans Candida species KW - vaginal epithelial cells KW - vulvovaginal candidiasis (VVC) SP - 894069 EP - 894069 JF - Frontiers in immunology JO - Front Immunol VL - 13 N2 - Vulvovaginal candidiasis (VVC) is characterized by symptomatic inflammatory responses in the vagina caused by Candida albicans and non-albicans Candida (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 C. albicans 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 C. albicans strain SC5314. This differs markedly from oral epithelial cells, which respond in a biphasic manner in order to properly discriminate the morphology of C. albicans. When compared with SC5314, a highly azole-resistant C. albicans isolate 1052 can induce a stronger phosphorylated signal of EGFR and p38, while clinically-isolated NAC strains including C. tropicalis, C. glabrata, C. parapsilosis and C. auris trigger higher levels of phosphorylated ERK1/2 and c-Fos than C. albicans. Inhibition of EGFR significantly reduces inflammatory response and epithelial damage induced by C. albicans both in vitro and in vivo, while inhibition of p38 leads to significant repair of epithelial damage triggered by both C. albicans and NAC species. These results confirm the importance of the EGFR-MAPK signaling in VVC pathogenesis and highlight the remarkable immunogenic differences between C. albicans and NAC species in host-microbe interactions. SN - 1664-3224 UR - https://www.unboundmedicine.com/medline/citation/35720274/Divergent_EGFR/MAPK-Mediated_Immune_Responses_to_Clinical_Candida_Pathogens_in_Vulvovaginal_Candidiasis. DB - PRIME DP - Unbound Medicine ER -