The yeast Candida albicans colonizes mucosal surfaces and is usually harmless. However, under certain conditions it can cause dangerous infections. A research team at the University of Zurich has now discovered how the immune system prevents the conversion from a harmless colonizer to a pathogenic one. This happens, among other things, with the binding of zinc.
The microbiome is not only made up of bacteria, but also fungi. Most of them support human and animal health. However, some fungi also have pathogenic potential. For example, yeast Candida albicans box they grow uncontrollably on the oral mucosa, causing oral thrush.
In severe cases, developing in filamentous form, it can enter the bloodstream and cause systemic infections, which are responsible for more than a million deaths annually. This occurs mainly in people with weakened immune systems in intensive care units, for example people who have been immunosuppressed due to a transplant or cancer.
Balance between friend and foe
The mechanisms that keep the fungus in check on our mucosa and prevent an infection remain poorly understood.”
Salomé LeibundGut-Landmann, Professor of Immunology at the Vetsuisse School, University of Zurich
Her team has now made two important discoveries: On the one hand they have shed light on how homeostasis is maintained through the delicate interplay between Candida albicans and the epithelial barrier on the one hand and the immune system on the other. For their studies, the researchers used different strains of it Candida albicans and mice.
A (sometimes) useful toxin
First, the team looked closely at the function of candidalysin, a toxin produced by the fungus that is known to directly attack host cells, thereby destroying the body’s protective surface. The researchers found that this factor, in small amounts, is necessary for the fungus to survive in the mouth. The fungus uses the toxin as a door opener to anchor itself to the lining of the oral cavity without causing damage.
“The fine-tuning of candidalysin determines whether Candida albicans shows beneficial or pathogenic properties,” so LeibundGut-Landmann. As a pathogen, the fungus produces large amounts of candidilysin. As a result, the immune system immediately reacts with severe inflammation. In its beneficial form, however, Candida albicans it produces only small amounts of the toxin and thus can remain inconspicuous on 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 drives the defense
In their second study, the researchers asked how Candida albicans it shifts from a harmless fungus to a pathogen in a weakened immune system. They hypothesized that the immune factor interleukin 17 plays an important role in this process – because people with a defect in the interleukin 17 gene develop oral thrush.
The results show that immunity induced by interleukin 17 prevents the fungus from growing in very large numbers. It also prevents the production of large amounts of candilysin and the transition to the pathogenic form.
Fungus in withdrawal
This happens, among other things, through a little-known mechanism called “nutritional immunity”: interleukin 17 indirectly binds zinc away from the fungus. Zinc is an important factor needed by the fungus to form penetrating hyphae and produce candidalysin. “So interleukin 17 is a gatekeeper that ensures Candida albicans remains harmless. The loss of this gate triggers a cascade that leads to fungal changes, tissue damage and chronic disease,” says LeibundGut-Landmann.
Results worth the price
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 an award by the Faculty of Science for his outstanding thesis. The award ceremony took place on December 12, 2025.
Source:
Journal References:
