Candidalysin activates innate epithelial immune responses via epidermal growth factor receptor

被引:0
|
作者
Jemima Ho
Xuexin Yang
Spyridoula-Angeliki Nikou
Nessim Kichik
Andrew Donkin
Nicole O. Ponde
Jonathan P. Richardson
Remi L. Gratacap
Linda S. Archambault
Christian P. Zwirner
Celia Murciano
Rhonda Henley-Smith
Selvam Thavaraj
Christopher J. Tynan
Sarah L. Gaffen
Bernhard Hube
Robert T. Wheeler
David L. Moyes
Julian R. Naglik
机构
[1] King’s College London,Centre for Host
[2] Imperial College London,Microbiome Interactions, Faculty of Dental, Oral and Craniofacial Sciences
[3] University of Maine,Department of Life Sciences
[4] King’s College London,Department of Molecular & Biomedical Science
[5] Rutherford Appleton Laboratory,Centre for Oral, Clinical & Translational Science, Faculty of Dental, Oral and Craniofacial Sciences
[6] University of Pittsburgh,Central Laser Facility, Science and Technology Facilities Council, Research Complex at Harwell
[7] Hans Knöll Institute,Division of Rheumatology and Clinical Immunology
[8] Friedrich Schiller University,Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology
[9] University of Maine,Graduate School of Biomedical Sciences and Engineering
[10] The Francis Crick Institute,Protein Phosphorylation Lab
[11] University of Edinburgh,Roslin Institute
[12] Productos Citrosol,Postharvest Technology Department
来源
关键词
D O I
暂无
中图分类号
学科分类号
摘要
Candida albicans is a fungal pathobiont, able to cause epithelial cell damage and immune activation. These functions have been attributed to its secreted toxin, candidalysin, though the molecular mechanisms are poorly understood. Here, we identify epidermal growth factor receptor (EGFR) as a critical component of candidalysin-triggered immune responses. We find that both C. albicans and candidalysin activate human epithelial EGFR receptors and candidalysin-deficient fungal mutants poorly induce EGFR phosphorylation during murine oropharyngeal candidiasis. Furthermore, inhibition of EGFR impairs candidalysin-triggered MAPK signalling and release of neutrophil activating chemokines in vitro, and diminishes neutrophil recruitment, causing significant mortality in an EGFR-inhibited zebrafish swimbladder model of infection. Investigation into the mechanism of EGFR activation revealed the requirement of matrix metalloproteinases (MMPs), EGFR ligands and calcium. We thus identify a PAMP-independent mechanism of immune stimulation and highlight candidalysin and EGFR signalling components as potential targets for prophylactic and therapeutic intervention of mucosal candidiasis.
引用
收藏
相关论文
共 50 条
  • [41] Parkin activates innate immunity and promotes antitumor immune responses
    Perego, Michela
    Yeon, Minjeong
    Agarwal, Ekta
    Milcarek, Andrew T.
    Bertolini, Irene
    Camisaschi, Chiara
    Ghosh, Jagadish C.
    Tang, Hsin-Yao
    Grandvaux, Nathalie
    Ruscetti, Marcus
    Kossenkov, Andrew, V
    Preston-Alp, Sarah
    Tempera, Italo
    Auslander, Noam
    Altieri, Dario C.
    JOURNAL OF CLINICAL INVESTIGATION, 2024, 134 (22):
  • [42] The dynamic expression of the epidermal growth factor receptor and epidermal growth factor ligand family in a differentiating intestinal epithelial cell line
    Kuwada, SK
    Li, XF
    Damstrup, L
    Dempsey, PJ
    Coffey, RJ
    Wiley, HS
    GROWTH FACTORS, 1999, 17 (02) : 139 - 153
  • [43] Humoral immune response to epidermal growth factor receptor in lung cancer
    Yulin Wang
    Fenghui Liu
    Songyun OuYang
    Man Liu
    Xue Zhang
    Peng Wang
    Chunling Zhao
    Liguo Zhang
    Liping Dai
    Immunologic Research, 2021, 69 : 71 - 80
  • [44] Hepatocyte growth factor induces epithelial cell motility through transactivation of the epidermal growth factor receptor
    Spix, Julie K.
    Chay, Edward Y.
    Block, Ethan R.
    Klarlund, Jes K.
    EXPERIMENTAL CELL RESEARCH, 2007, 313 (15) : 3319 - 3325
  • [45] Humoral immune response to epidermal growth factor receptor in lung cancer
    Wang, Yulin
    Liu, Fenghui
    OuYang, Songyun
    Liu, Man
    Zhang, Xue
    Wang, Peng
    Zhao, Chunling
    Zhang, Liguo
    Dai, Liping
    IMMUNOLOGIC RESEARCH, 2021, 69 (01) : 71 - 80
  • [46] Prolidase Directly Binds and Activates Epidermal Growth Factor Receptor and Stimulates Downstream Signaling
    Yang, Lu
    Li, Yun
    Ding, Yi
    Choi, Kyoung-Soo
    Kazim, A. Latif
    Zhang, Yuesheng
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2013, 288 (04) : 2365 - 2375
  • [47] Protease-activated receptor-2 activation enhances epithelial wound healing via epidermal growth factor receptor
    Bandara, Mahesha
    MacNaughton, Wallace K.
    TISSUE BARRIERS, 2022, 10 (02):
  • [48] Epidermal growth factor enhances mineralocorticoid receptor transactivation via deubiquitylation of the receptor
    Mitsuishi, Yuko
    Shibata, Hirotaka
    Kurihara, Isao
    Yokota, Kenichi
    Murai-Takeda, Ayano
    Jo, Rie
    Hayashi, Takeshi
    Motosugi, Yuichiro
    Itoh, Hiroshi
    ENDOCRINE JOURNAL, 2010, 57 : S549 - S549
  • [49] Human eosinophils induce mucin production in airway epithelial cells via epidermal growth factor receptor activation
    Burgel, PR
    Lazarus, SC
    Tam, DCW
    Ueki, IF
    Atabai, K
    Birch, M
    Nadel, JA
    JOURNAL OF IMMUNOLOGY, 2001, 167 (10): : 5948 - 5954
  • [50] Recurrent exposure to nicotine differentiates human bronchial epithelial cells via epidermal growth factor receptor activation
    Martinez-Garcia, Eva
    Irigoyen, Marta
    Anso, Elena
    Martinez-Irujo, Juan Jose
    Rouzaut, Ana
    TOXICOLOGY AND APPLIED PHARMACOLOGY, 2008, 228 (03) : 334 - 342