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Divergent EGFR/MAPK-Mediated Immune Responses to Clinical Candida Pathogens in Vulvovaginal Candidiasis
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 resp...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204526/ https://www.ncbi.nlm.nih.gov/pubmed/35720274 http://dx.doi.org/10.3389/fimmu.2022.894069 |
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author | Zhang, Jingyun Peng, Jingwen Li, Dongmei Mei, Huan Yu, Yu Li, Xiaofang She, Xiaodong Liu, Weida |
author_facet | Zhang, Jingyun Peng, Jingwen Li, Dongmei Mei, Huan Yu, Yu Li, Xiaofang She, Xiaodong Liu, Weida |
author_sort | Zhang, Jingyun |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9204526 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92045262022-06-18 Divergent EGFR/MAPK-Mediated Immune Responses to Clinical Candida Pathogens in Vulvovaginal Candidiasis Zhang, Jingyun Peng, Jingwen Li, Dongmei Mei, Huan Yu, Yu Li, Xiaofang She, Xiaodong Liu, Weida Front Immunol Immunology 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. Frontiers Media S.A. 2022-05-26 /pmc/articles/PMC9204526/ /pubmed/35720274 http://dx.doi.org/10.3389/fimmu.2022.894069 Text en Copyright © 2022 Zhang, Peng, Li, Mei, Yu, Li, She and Liu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Zhang, Jingyun Peng, Jingwen Li, Dongmei Mei, Huan Yu, Yu Li, Xiaofang She, Xiaodong Liu, Weida Divergent EGFR/MAPK-Mediated Immune Responses to Clinical Candida Pathogens in Vulvovaginal Candidiasis |
title | Divergent EGFR/MAPK-Mediated Immune Responses to Clinical Candida Pathogens in Vulvovaginal Candidiasis |
title_full | Divergent EGFR/MAPK-Mediated Immune Responses to Clinical Candida Pathogens in Vulvovaginal Candidiasis |
title_fullStr | Divergent EGFR/MAPK-Mediated Immune Responses to Clinical Candida Pathogens in Vulvovaginal Candidiasis |
title_full_unstemmed | Divergent EGFR/MAPK-Mediated Immune Responses to Clinical Candida Pathogens in Vulvovaginal Candidiasis |
title_short | Divergent EGFR/MAPK-Mediated Immune Responses to Clinical Candida Pathogens in Vulvovaginal Candidiasis |
title_sort | divergent egfr/mapk-mediated immune responses to clinical candida pathogens in vulvovaginal candidiasis |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204526/ https://www.ncbi.nlm.nih.gov/pubmed/35720274 http://dx.doi.org/10.3389/fimmu.2022.894069 |
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