Projects per year
Abstract
Candida albicans is a commensal of the urogenital tract and the predominant cause of vulvovaginal candidiasis (VVC). Factors that increase circulatory estrogen levels such as pregnancy, the use of oral contraceptives, and hormone replacement therapy predispose women to VVC, but the reasons for this are largely unknown. Here, we investigate how adaptation of C. albicans to estrogen impacts the fungal host-pathogen interaction. Estrogen promotes fungal virulence by enabling C. albicans to avoid the actions of the innate immune system. Estrogen-induced innate immune evasion is mediated via inhibition of opsonophagocytosis through enhanced acquisition of the human complement regulatory protein, Factor H, on the fungal cell surface. Estrogen-induced accumulation of Factor H is dependent on the fungal cell surface protein Gpd2. The discovery of this hormone-sensing pathway might pave the way in explaining gender biases associated with fungal infections and may provide an alternative approach to improving women's health.
Original language | English |
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Article number | 110183 |
Number of pages | 11 |
Journal | Cell Reports |
Volume | 38 |
Issue number | 1 |
DOIs | |
Publication status | Published - 4 Jan 2022 |
Bibliographical note
Funding Information:We would like to thank the fungal community for the donation of fungal strains, Prof. G. Brown (University of Exeter) for FC-Dectin-1, Prof. G. Ramage for clinical isolates, the Environmental Omics facility at the University of Birmingham for help with the RNA sequencing, as well as Elizabeth Ballou (University of Birmingham) for critical reading of the manuscript, and Prof. A. Mitchell for providing access to raw data from Nobile and Mitchell (2005). P.K. is funded by the Wellcome Trust strategic award for medical mycology (097377/Z/11/Z), F.C. and R.A.H. are funded by the MRC (MR/L00903X/1) and BBSRC (BB/R00966X/1), A.C.H. is funded by the BBSRC (BB/R00966X/2), and D.K. is funded by the Graduate Training Program at the University of Kent. P.K. F.C. B.K. H.G. A.C.H. and D.K. conducted the experiments; F.C. and H.-J.T. conducted the bioinformatics analysis; R.A.H. conceived the idea and designed the experiments; R.A.H. wrote the paper. The authors declare no competing interests. We worked to ensure gender balance in the recruitment of human subjects. We worked to ensure ethnic or other types of diversity in the recruitment of human subjects. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as an underrepresented ethnic minority in science. One or more of the authors of this paper received support from a program designed to increase minority representation in science. The author list of this paper includes contributors from the location where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.
Publisher Copyright:
© 2021 The Authors
Keywords
- Candida albicans
- complement
- Factor H
- Gpd2
- hormone sensing
- Innate immune evasion
- oestrogen
- VVC
ASJC Scopus subject areas
- General Biochemistry,Genetics and Molecular Biology
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- 2 Finished
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De-cloaking the cell wall: investigating the molecular mechanism(s) of cell wall remodelling during adaptation to environmental pH in Candida albicans
Hall, R. (Principal Investigator)
Biotechnology & Biological Sciences Research Council
1/06/18 → 31/05/21
Project: Research Councils
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Fungal Neighbourhood Watch: Understanding how combinatorial signals from the host niche drive pathogenesis in candida albicans
Hall, R. (Principal Investigator)
1/03/14 → 28/02/19
Project: Research Councils