The microbiome not only consists of bacteria, but also of fungi. Most of them support human and animal health. However, some fungi also have pathogenic potential. For instance, the yeast Candida albicans can grow in an uncontrolled manner on the oral mucosa, causing oral thrush.
In severe cases by growing in a filamentous form it can enter the blood stream and cause systemic infections, which account for over one million deaths per year. This happens primarily in people with a weakened immune system on intensive care units, for instance individuals who are immunosuppressed because of a transplantation or cancer.
Balance between friend and foe
"The mechanisms that keep the fungus under control on our mucosa and prevent an infection remain poorly understood," says Salomé LeibundGut-Landmann, Professor of Immunology at the Vetsuisse Faculty of University Zurich. Her team has now made two important discoveries: On the one hand they shed light on how homeostasis is maintained through the fine-tuned interplay between Candida albicans and the epithelial barrier on the one hand, and the immune system on the other hand. For their studies the researchers used different strains of Candida albicans and mice.
A (sometimes) useful toxin
First, the team took a close look at the function of candidalysin, a toxin produced by the fungus, that is known to attack host cells directly, thereby damaging the protective surface of the body. The researchers found that this factor, in small amounts, is necessary for the fungus to survive in the mouth. The fungus uses the toxin like a door opener to anchor itself in the mucous membrane of the oral cavity without causing damage.
"The fine regulation of candidalysin determines whether Candida albicans exhibits beneficial or pathogenic properties," so LeibundGut-Landmann. As a pathogen, the fungus produces large amounts of candidalysin. As a result, the immune system reacts immediately with severe inflammation. In its beneficial form, however, Candida albicans produces only small amounts of the toxin and can thus remain inconspicuous in the mucous membrane. "The fungus drives with the handbrake on, so to speak. It needs a little toxin, but too much is immediately punished."
Interleukin leads defense
In their second study, the researchers asked how Candida albicans shifts from a harmless fungus to a pathogen in a weakened immune system. They assumed that the immune factor interleukin 17 plays an important role in this process − because individuals with a defect in the interleukin 17 gene develop oral thrush.
The results show that interleukin 17-mediated immunity prevents the fungus from growing in too large numbers. It also hampers the production of large quantities of candidalysin and the switch to the pathogenic form.
Fungus in withdrawal
This happens, among other things, through a little-known mechanism called 'nutritional immunity': interleukin 17 indirectly sequesters zinc away from the fungus. Zinc is an important factor that is needed by the fungus to form invasive hyphae and produce candidalysin. "Hence, interleukin 17 is a gatekeeper ensuring Candida albicans remains harmless. Loss of this gate triggers a cascade leading to fungal changes, tissue damage, and chronic disease," so LeibundGut-Landmann.
Price-worthy results
These findings are important considering the increased use of immunotherapies that block the interleukin 17 immune pathway to treat psoriasis and other inflammatory diseases. Not surprisingly, a fraction of patients receiving antibodies directed against interleukin 17 or its receptor develop mucocutaneous candidiasis including thrush as a side effect.
In recognition of the excellence of his work, the first author of both publications, Ricardo Froís-Martins, was awarded a prize from the Faculty of Science for his outstanding dissertation. The Award Ceremony took place on 12th December 2025.
Literature
Frois-Martin R, Lagler J, Schille TB, Elshafee O, Martinez de San Vicente K, Mertens S, Stokmaier M, Kilb I, Sertour N, Bachellier-Bassi S, Mogavero S, Sanglard D, d'Enfert C, Hube B, LeibundGut-Landmann S (2025). Dynamic Expression of the Fungal Toxin Candidalysin Governs Homeostatic Oral Colonization. 25 September 2025. Nature Microbiology. DOI: 10.1038/s41564-025-02122-4
Fróis-Martins R, Martinez de San Vicente K, Maufrais C, Mertens S, Sertour N, Sitterlé E, Bougnoux ME, d'Enfert C and LeibundGut-Landmann S (2025). IL-17-mediated antifungal immunity restricts Candida albicans pathogenicity in the oral cavity. 12 December 2025. Nature Microbiology. DOI: 10.1038/s41564-025-02198-y
