Local albumin excess exacerbates Candida albicans-induced inflammasome activation linked with hyperinflammation during vulvovaginal candidiasis
Abstract
Vulvovaginal candidiasis (VVC) is a mucosal yeast infection, mostly caused by Candida albicans, where symptoms are driven by inflammation. The onset of VVC is instigated by C. albicans pathogenicity, but the underlying causes of disease-driving hyperinflammation remain incompletely resolved. We found that vaginal albumin concentrations are higher in women with recurrent VVC and during experimental VVC in mice. These albumin levels correlated with inflammatory cytokines in vaginal lavages. While the abundance of this serum protein in the vagina can be a hallmark of inflammation-induced vascular permeability, we reveal molecular mechanisms by which albumin can also drive inflammation. Albumin increased NLRP3 inflammasome activation in human macrophages elicited by C. albicans. This was associated with increased resistance of C. albicans to macrophage-mediated clearance in the presence of albumin. Further, albumin increased the expression of fungal secreted aspartic protease 1, which we identified as the effector driving inflammasome activation and IL-1β responses in vitro and in an in vivo VVC model. Moreover, neutrophils also exhibited impaired clearance of C. albicans in the presence of albumin. Collectively, vaginal albumin may not only be a consequence of inflammation of the vaginal mucosa, but also can drive C. albicans-induced hyperinflammatory IL-1β responses that underlie immunopathology in VVC.
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BibTeX
@article{austermeier2026local,
title = {{Local albumin excess exacerbates Candida albicans-induced inflammasome activation linked with hyperinflammation during vulvovaginal candidiasis}},
author = {Sophie Austermeier and Kar On Cheng and Axel Dietschmann and Gianluca Vascelli and Dolly E. Montaño and Sophia U. J. Hitzler and Kira S. Skurk and Candela Fernández-Fernández and Saloni Saloni and Stefanie Westermann and Martin Jaeger and Nadja Jablonowski and Stephanie Wisgott and Osama Elshafee and Chiara Brachelente and Dennis M. de Graaf and Tomasz Próchnicki and Eicke Latz and Stefan Wirtz and Christoph Becker and Giorgia Renga and Vasileios Oikonomou and Bernhard Hube and Gilbert G. G. Donders and Marina Pekmezovic and Teresa Zelante and Mark S. Gresnigt},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78761-w},
url = {https://www.nature.com/articles/s41467-026-78761-w},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Local albumin excess exacerbates Candida albicans-induced inflammasome activation linked with hyperinflammation during vulvovaginal candidiasis
AU - Sophie Austermeier
AU - Kar On Cheng
AU - Axel Dietschmann
AU - Gianluca Vascelli
AU - Dolly E. Montaño
AU - Sophia U. J. Hitzler
AU - Kira S. Skurk
AU - Candela Fernández-Fernández
AU - Saloni Saloni
AU - Stefanie Westermann
AU - Martin Jaeger
AU - Nadja Jablonowski
AU - Stephanie Wisgott
AU - Osama Elshafee
AU - Chiara Brachelente
AU - Dennis M. de Graaf
AU - Tomasz Próchnicki
AU - Eicke Latz
AU - Stefan Wirtz
AU - Christoph Becker
AU - Giorgia Renga
AU - Vasileios Oikonomou
AU - Bernhard Hube
AU - Gilbert G. G. Donders
AU - Marina Pekmezovic
AU - Teresa Zelante
AU - Mark S. Gresnigt
PY - 2026
DA - 2026/10/29
JO - Nature Communications
DO - 10.1038/s41467-026-78761-w
UR - https://www.nature.com/articles/s41467-026-78761-w
AB - Vulvovaginal candidiasis (VVC) is a mucosal yeast infection, mostly caused by Candida albicans, where symptoms are driven by inflammation. The onset of VVC is instigated by C. albicans pathogenicity, but the underlying causes of disease-driving hyperinflammation remain incompletely resolved. We found that vaginal albumin concentrations are higher in women with recurrent VVC and during experimental VVC in mice. These albumin levels correlated with inflammatory cytokines in vaginal lavages. While the abundance of this serum protein in the vagina can be a hallmark of inflammation-induced vascular permeability, we reveal molecular mechanisms by which albumin can also drive inflammation. Albumin increased NLRP3 inflammasome activation in human macrophages elicited by C. albicans. This was associated with increased resistance of C. albicans to macrophage-mediated clearance in the presence of albumin. Further, albumin increased the expression of fungal secreted aspartic protease 1, which we identified as the effector driving inflammasome activation and IL-1β responses in vitro and in an in vivo VVC model. Moreover, neutrophils also exhibited impaired clearance of C. albicans in the presence of albumin. Collectively, vaginal albumin may not only be a consequence of inflammation of the vaginal mucosa, but also can drive C. albicans-induced hyperinflammatory IL-1β responses that underlie immunopathology in VVC.
SN - 2041-1723
ER -