Local albumin excess exacerbates Candida albicans-induced inflammasome activation linked with hyperinflammation during vulvovaginal candidiasis
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.
Authors
- Vasileios Oikonomou (ORCID: https://orcid.org/0000-0002-7553-0159)
- Christoph Becker (ORCID: https://orcid.org/0000-0002-1388-1041)
- Stefan J. Wirtz (ORCID: https://orcid.org/0000-0001-6936-7431)
- Kar On Cheng (ORCID: https://orcid.org/0000-0002-9127-1900)
- Eicke Latz (ORCID: https://orcid.org/0000-0003-1488-5666)
- Bernhard Hube (ORCID: https://orcid.org/0000-0002-6028-0425)
- Nadja Jablonowski
- Mark S. Gresnigt (ORCID: https://orcid.org/0000-0002-9514-4634)
- Martin Jaeger (ORCID: https://orcid.org/0000-0002-7709-2869)
- Stephanie Wisgott
- Kira Skurk
- Giorgia Renga (ORCID: https://orcid.org/0000-0002-9762-6493)
- Chiara Brachelente (ORCID: https://orcid.org/0000-0002-4812-3216)
- Sophie Austermeier (ORCID: https://orcid.org/0000-0002-1048-5983)
- Tomasz Próchnicki
- Dolly E. Montaño (ORCID: https://orcid.org/0000-0002-7714-987X)
- Osama Elshafee
- Teresa Zelante (ORCID: https://orcid.org/0000-0002-7071-0302)
- Sophia U J Hitzler (ORCID: https://orcid.org/0000-0002-3582-2544)
- Stefanie Westermann (ORCID: https://orcid.org/0000-0003-4977-0009)
- Dennis Marinus de Graaf (ORCID: https://orcid.org/0000-0002-9198-7159)
- Axel Dietschmann (ORCID: https://orcid.org/0000-0002-0598-9714)
- Gianluca Vascelli
- Candela Fernández-Fernández (ORCID: https://orcid.org/0000-0002-3277-7522)
- Marina Pekmezovic
- Gilbert G. G. Donders
- Saloni Saloni
Institutions
- University of Bonn (DE)
- Radboud University Nijmegen (NL)
- German Cancer Research Center (DE)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- University of Perugia (IT)
- Radboud University Medical Center (NL)
- Universitätsklinikum Erlangen (DE)
- German Rheumatism Research Centre (DE)
- Antwerp University Hospital (BE)
- Radboud Institute for Molecular Life Sciences (NL)
- Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI) (DE)
- Technical University of Munich (DE)
- Friedrich Schiller University Jena (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-10-29
- DOI
- https://doi.org/10.1038/s41467-026-78761-w
- Primary Topic
- Inflammasome and immune disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Freistaat Thüringen
- European Commission
- Radboud Universitair Medisch Centrum