1. Oestrogen promotes innate immune evasion of Candida albicans through inactivation of the alternative complement system
- Author
-
Pizga Kumwenda, Fabien Cottier, Alexandra C. Hendry, Davey Kneafsey, Ben Keevan, Hannah Gallagher, Hung-Ji Tsai, and Rebecca A. Hall
- Subjects
Glycerol-3-Phosphate Dehydrogenase (NAD+) ,Virulence ,Factor H ,Complement Pathway, Alternative ,hormone sensing ,Estrogens ,General Biochemistry, Genetics and Molecular Biology ,Article ,Immunity, Innate ,Innate immune evasion ,QR ,Gpd2 ,Phagocytosis ,Complement Factor H ,Candida albicans ,QR180 ,Humans ,complement ,Female ,oestrogen ,VVC ,Candidiasis, Vulvovaginal ,Progesterone ,Immune Evasion - Abstract
Summary 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., Graphical abstract, Highlights • Estrogen promotes the virulence of Candida albicans by reducing phagocytosis • Estrogen-adapted C. albicans binds more Factor H on its cell surface • Estrogen-induced innate immune evasion of C. albicans is dependent on Gpd2 • Overexpression of GPD2 promotes the virulence of C. albicans, Women with high estrogen levels have an increased risk of developing genital thrush caused by Candida albicans. Kumwenda et al. show that C. albicans grown in estrogen is not recognized and killed efficiently by white blood cells. This reduced immune recognition could enable C. albicans to proliferate and cause infection.
- Published
- 2022