- Researchers in the University of Sheffield's Bateson Centre for Disease Mechanisms have discovered that Candida albicans fungus can disable white blood cells
- An estimated 40-60 per cent of healthy people carry Candida albicans harmlessly but it can be deadly for people with weakened immune systems
- The findings may pave the way for new therapies to tackle life-threatening fungal infections and rising antifungal resistance
Researchers at the University of Sheffield have discovered that a fungus deadly to people with weakened immune systems can disable a critical defence used by neutrophils, the body's front-line infection-fighting white blood cells.
An estimated 40 to 60 per cent of healthy people carry Candida albicans harmlessly as part of the body's normal microbial community.
But in people with weakened immune systems it can enter the bloodstream and trigger invasive candidiasis, a condition with mortality rates approaching 50 per cent.
The research conducted using zebrafish models and human immune cells showed that restoring this suppressed immune response dramatically improved survival from infection, particularly when combined with existing antifungal drugs.
The findings, from scientists at Sheffield's Bateson Centre for Disease Mechanisms, could lead to new therapies to tackle life-threatening fungal infections and rising antifungal resistance.
Candida was found to actively suppress production of reactive nitrogen species (RNS), toxic molecules normally used by neutrophils (our most abundant white blood cell) to kill invading microbes. Remarkably, the fungus reduced these protective molecules to levels below normal baseline activity, effectively dampening the immune response during infection.
The study found similar immune suppression was observed in other clinically important fungal pathogens, including the emerging multidrug-resistant species Candida auris.
The World Health Organization has designated Candida albicans and Candida auris as critical priority fungal pathogens because of increasing drug resistance and the lack of effective vaccines or treatments.
The researchers found that the more effectively a fungal strain suppressed neutrophil RNS, the more deadly the infection became in the animal model, suggesting immune suppression is an important driver of fungal virulence.
The findings point towards the possibility of 'host-directed therapies', treatments that strengthen the patient's own immune response rather than attacking the fungus directly. Such approaches may become increasingly important as antifungal resistance rises worldwide and treatment options remain limited.
Dr Philip Elks, Senior Lecturer at the University of Sheffield's School of Medicine and Population Health, and Co-Director of the Bateson Centre for Disease Mechanisms, said: "Candida infection can be lethal for patients with compromised immune systems and the global increase in antifungal resistance along with limited treatment options is of immense concern.
"Although in its early stages, our findings indicate we could help patients fight off fungal infections by strengthening their immune systems, protecting vulnerable people from the deadly outcomes of fungal infections."
Future work will now focus on identifying precisely how Candida disables neutrophil function and whether RNS targeting therapies could eventually be translated into clinical use alongside conventional antifungal drugs.
