How Our Immune System Keeps Candida albicans in Check

Zinc Deprivation Inhibits Fungal Infection of Mucous Membranes

A Matter of Balance: The yeast Candida albicans colonizes our mucous membranes. Researchers have now discovered why this is highly dangerous under certain conditions, but remains harmless in most cases. According to their findings, the immune system deprives the fungus of the necessary zinc, thereby inhibiting both toxin production and the proliferation of yeast cells. However, if the immune system is weakened, Candida can transform into a deadly pathogen.

The yeast Candida albicans (blue) breaks out of human immune cells (red) by forming long, thread-like cells called hyphae. The part of the hypha that has already left the immune cells is stained yellow. © Erik Böhm, Leibniz-HKI

Countless microbes live on and in our bodies, essential for our health. This microbiome includes the skin flora, as well as bacteria and fungi that live on our mucous membranes in the mouth, intestines, and vagina. Among these is the yeast Candida albicans. An infection of the oral mucosa with this fungus is usually harmless. Approximately three-quarters of all people carry it without realizing it.

Sometimes, however, the fungus can grow uncontrollably and form painful, itchy patches in the mouth, a condition known as thrush or candidiasis. In severe cases, thread-like fungal hyphae enter the bloodstream and cause systemic infections. Every year, over a million people die from such a Candida infection, primarily those with weakened immune systems who require intensive care.

How dangerous is the toxin produced by Candida albicans?

But what factors determine whether Candida albicans grows moderately or uncontrollably? A team led by Ricardo Fróis-Martins from the University of Zurich has now investigated the mechanisms that keep the fungus in check on our mucous membranes and prevent infection. To do this, the researchers used various genetically modified strains of Candida albicans, as well as human and mouse cells. They analyzed how the yeast and the mucous membrane of the tongue interact.

In particular, the team examined the function of the fungal toxin candidalysin, which the yeast produces and secretes. This peptide toxin is known to theoretically attack human cells and create holes in their membranes. However, the extent to which the toxin actually damages skin epithelial tissue was previously unclear.

Dosage of the fungal toxin is crucial

Laboratory tests have now revealed that Candida albicans uses this toxin molecule to anchor itself in the host's mucous membrane with its hyphae. This helps the fungus survive. The cells of the mucous membrane are not affected by it—provided the toxin is present only in small amounts, as Fróis-Martins and his colleagues discovered.

If, on the other hand, the fungus produces large amounts of candidalysin, it damages the mucous membranes. The immune system then reacts with severe inflammation. "The fine-tuning of candidalysin determines whether Candida albicans becomes a harmless colonizer or a pathogen," concludes senior author Salomé LeibundGut-Landmann from the University of Zurich.

Immune System Keeps Yeast Cells in Check

But under what circumstances does Candida albicans ramp up its toxin production and transform from a harmless fungus into a pathogen? Biomedical researchers investigated this in a second study using cell cultures and mice with weakened immune systems. They focused particularly on the role of the immune messenger interleukin-17, which the researchers suspected played a key role.

The tests revealed that the signaling molecule interleukin-17 inhibits the production of candidalysin in the yeast cells. It also triggers an immune response that slows down the proliferation of the yeast cells. In both cases, interleukin-17 indirectly deprives the fungus of zinc, which it needs for the production of the toxin and its thread-like hyphae, as Fróis-Martins' team discovered.

Explanation for Common Disease Patterns

The fungus Candida albicans is thus deprived of zinc by interleukin-17 and thereby kept in check. “Interleukin-17 acts like a gatekeeper, ensuring that Candida albicans remains harmless,” says LeibundGut-Landmann. This explains why people with a genetic defect in the interleukin-17 blueprint so often suffer from oral thrush.

The finding also explains why immunocompromised individuals often develop severe Candida infections: In many immunotherapies, such as those for psoriasis, the interleukin-17 immune pathway is blocked by therapeutic antibodies. Oral candidiasis often occurs as a side effect. (Nature Microbiology, 2025; doi: 10.1038/s41564-025-02122-4 and doi: 10.1038/s41564-025-02198-y)

Source: University of Zurich