Understanding how fungi mediate disease

Humans have evolved intimate symbiotic relationships with fungi and individual variations in the mycobiome (i.e, the fungal community within the body) influence host health and disease. The fact that fungi are capable of colonizing almost every niche within the human body suggests that they must possess particular immune adaptation mechanisms, the breakdown of which may result in fatal fungal infections and severe fungal diseases. This indicates that the susceptibility to fungal infections and diseases depends on an underlying deregulated inflammatory immunity.

The EU-funded ALLFUN (Fungi in the setting of inflammation, allergy and autoimmune diseases: Translating basic science into clinical practices) project set out to characterise the cellular and molecular mechanisms by which airborne or commensal fungi contribute to immune homeostasis or its deregulation. In this context, the consortium followed a multidisciplinary systems biology approach, which combined fungal genetics, clinical research and animal models. The work focused on yeasts and filamentous fungi known to cause a number of chronic inflammatory, autoimmune and allergic diseases.

Researchers identified and characterised fungal immunogenic molecules, including proteins, cell wall polysaccharides and lipids. These served in the development of ultrasensitive diagnostic kits, thereby addressing an urgent unmet medical need.

Studies on immune cells helped scientists identify the signalling pathways that get activated by distinct pathogen-associated molecular patterns or by tissue damage-associated molecular patterns. The kynurenines-to-tryptophan ratio proved to be a good indicator of a patient's ability to cope with fungus-driven inflammation. Further insight into the strategies of fungal immune evasion might help design antifungal vaccines, while interventions such as novel CCR4 antagonists could soon translate into clinical practice.

A significant achievement of the ALLFUN study was the discovery of several single nucleotide polymorphisms implicated in inflammatory fungal diseases. The identification of susceptibility genes in patients at risk of chronic fungal infections will improve patient stratification and facilitate tailored treatment.

Collectively, the deliverables and findings of the ALLFUN study will contribute to more efficient treatment of fungal infections.