Lactic acid in the vaginal milieu modulates the <i>Candida</i> -host interaction
Vulvovaginal candidiasis (VVC) is one of the most common infections caused by <i>Candida albicans</i>. VVC is characterized by an inadequate hyperinflammatory response and clinical symptoms associated with <i>Candida</i> colonization of the vaginal mucosa. Compared to other host niches in which <i>C. albicans</i> can cause infection, the vaginal environment is extremely rich in lactic acid that is produced by the vaginal microbiota. We examined how lactic acid abundance in the vaginal niche impacts the interaction between <i>C. albicans</i> and the human immune system using an <i>in vitro</i> culture in vaginal simulative medium (VSM). The presence of lactic acid in VSM (VSM+LA) increased <i>C. albicans</i> proliferation, hyphal length, and its ability to cause damage during subsequent infection of vaginal epithelial cells. The cell wall of <i>C. albicans</i> cells grown in VSM+LA displayed a robust mannan fibrillar structure, β-glucan exposure, and low chitin content. These cell wall changes were associated with altered immune responses and an increased ability of the fungus to induce trained immunity. Neutrophils were compromised in clearing <i>C. albicans</i> grown in VSM+LA conditions, despite mounting stronger oxidative responses. Collectively, we found that fungal adaptation to lactic acid in a vaginal simulative context increases its immunogenicity favouring a pro-inflammatory state. This potentially contributes to the immune response dysregulation and neutrophil recruitment observed during recurrent VVC.
Authors
- Ian Leaves (ORCID: https://orcid.org/0000-0002-5612-9087)
- Neil A. R. Gow (ORCID: https://orcid.org/0000-0002-2776-5850)
- Bernhard Hube (ORCID: https://orcid.org/0000-0002-6028-0425)
- Mark S. Gresnigt (ORCID: https://orcid.org/0000-0002-9514-4634)
- Alistair J. P. Brown (ORCID: https://orcid.org/0000-0003-1406-4251)
- Leo A. B. Joosten (ORCID: https://orcid.org/0000-0001-6166-9830)
- Marisa Valentine (ORCID: https://orcid.org/0000-0001-5627-3196)
- Mark H. T. Stappers (ORCID: https://orcid.org/0000-0003-4154-7160)
- Arnab Pradhan (ORCID: https://orcid.org/0000-0003-4328-3912)
- Diletta Rosati (ORCID: https://orcid.org/0000-0003-2992-2503)
- Mariolina Bruno (ORCID: https://orcid.org/0000-0002-5353-7691)
- Frank L. van de Veerdonk (ORCID: https://orcid.org/0000-0002-1121-4894)
- Axel Dietschmann (ORCID: https://orcid.org/0000-0002-0598-9714)
- Martin Jaeger (ORCID: https://orcid.org/0000-0001-6994-493X)
- S Roy (ORCID: https://orcid.org/0000-0003-2091-0688)
- Mihai G. Netea
Institutions
- University of Bonn (DE)
- Radboud University Nijmegen (NL)
- Schiller International University (FR)
- Iuliu Hațieganu University of Medicine and Pharmacy (RO)
- University of Exeter (GB)
- University Medical Center (US)
- Radboud University Medical Center (NL)
- Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI) (DE)
- Friedrich Schiller University Jena (DE)
- Medical Research Council (GB)
Publication Details
- Journal
- Virulence
- Published
- 2025-01-22
- DOI
- https://doi.org/10.1080/21505594.2025.2451165
- Citations
- 7
- Primary Topic
- Immune responses and vaccinations
- Type
- article
- Field-Weighted Citation Impact
- 5.58
Funders
- Wellcome Trust
- Freistaat Thüringen
- National Institute for Health and Care Research
- Department of Health and Social Care
- European Commission
- Deutsche Forschungsgemeinschaft
- ZonMw
- Boehringer Ingelheim Stiftung
- Medical Research Council Centre for Medical Mycology
- Horizon 2020 Framework Programme
- Medical Research Council