Things you wanted to know about fungal extracellular vesicles (but were afraid to ask)

Summary

Fungal extracellular vesicles (EVs) are tiny packages released by fungal cells that play important roles in fungal infections and how our immune system responds to them. Scientists have confirmed these EVs are real biological structures, not laboratory artifacts, and discovered they are produced by many different fungal species. Interestingly, these EVs can have opposite effects on the immune system depending on the fungus involved—sometimes helping our bodies fight infection and sometimes making infections worse, making them both potential vaccines and virulence factors.

Background

Fungal diseases claim more than 2 million lives annually yet remain understudied compared to other infectious diseases. Fungal extracellular vesicles (EVs) were discovered in 2007 and represent nanosized membranous particles (50-1000 nm) that influence immune response, pathogenesis, drug resistance, and biofilm formation. This perspective addresses fundamental questions about fungal EVs that have emerged as research in this field has expanded exponentially.

Objective

To address fundamental questions about fungal extracellular vesicles of particular interest to newcomers and curious researchers. The authors explore whether fungal EVs are real or artifacts, if all fungi produce them, appropriate nomenclature, practical considerations for working with them, and their paradoxical effects on host immunity.

Results

Extensive experimental evidence confirms fungal EVs are products of physiological molecular export mechanisms, not artifacts. EV production has been documented in 32 fungal species with no negative results reported. Fungal EVs display paradoxical immunological effects: they can enhance antifungal immunity through pattern recognition receptors or suppress it depending on species, composition, and experimental conditions.

Conclusion

Fungal extracellular vesicles represent real, regulated cellular structures with widespread production across fungal species. While significant progress has been made in isolation protocols and understanding their immunological roles, critical gaps remain regarding biogenesis mechanisms, standardized nomenclature, and the contradictory effects on host immunity. Further research is essential given the potential of fungal EVs as vaccine candidates and their roles in pathogenesis.
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