Immunomodulatory Potential of Fungal Extracellular Vesicles: Insights for Therapeutic Applications

Abstract

Extracellular vesicles (EVs) are membranous vesicular organelles that perform a variety of biological functions including cell communication across different biological kingdoms. EVs of mammals and, to a lesser extent, bacteria have been deeply studied over the years, whereas investigations of fungal EVs are still in their infancy. Fungi, encompassing both yeast and filamentous forms, are increasingly recognized for their production of extracellular vesicles (EVs) containing a wealth of proteins, lipids, and nucleic acids. These EVs play pivotal roles in orchestrating fungal communities, bolstering pathogenicity, and mediating interactions with the environment. Fungal EVs have emerged as promising candidates for innovative applications, not only in the management of mycoses but also as carriers for therapeutic molecules. Yet, numerous questions persist regarding fungal EVs, including their mechanisms of generation, release, cargo regulation, and discharge. This comprehensive review delves into the present state of knowledge regarding fungal EVs and provides fresh insights into the most recent hypotheses on the mechanisms driving their immunomodulatory properties. Furthermore, we explore the considerable potential of fungal EVs in the realms of medicine and biotechnology. In the foreseeable future, engineered fungal cells may serve as vehicles for tailoring cargo- and antigen-specific EVs, positioning them as invaluable biotechnological tools for diverse medical applications, such as vaccines and drug delivery.

Yeast strains isolated from fermented beverage produce extracellular vesicles with anti-inflammatory effects

“…In fungi, several studies prove that RNA interference is mediated by fungal EVs in models of plant infection 22 , 56 and in a study on mosquitoes 23 . However, as far as we know, there is no evidence of fungal EVs that show RNA interference in human cells 57 . In our study, we sought to find a possible RNA-mediated mechanism exerted by the EVs cargo, underlying the observed strong anti-inflammatory effect on human DCs.…”

Characterization and immunomodulatory potential of extracellular vesicles from non-pathogenic yeast strains

“…In fungi, several studies prove that RNA interference is mediated by fungal EVs in models of plant infection 21,42 and in a study on mosquitoes 22 . However, as far as we know, there is no evidence of fungal EVs that show RNA interference in human cells 43 . In our study, we sought to nd a possible RNA-mediated mechanism exerted by the EVs cargo, underlying the observed strong anti-in ammatory effect on human DCs.…”

Microbial extracellular vesicles contribute to antimicrobial resistance

“…It is noteworthy that compared to bacterial EVs, the EVs produced by fungi and parasites are more akin to the EVs of mammalian cells in types and biogenesis. The prevailing view holds that fungal and parasitic EVs can be classified into 2 categories: exosomes and ectosomes [ 24 , 25 ]. Exosomes range in size from 30 to 100 nm and their formation process involves: the plasma membrane invaginates to form endosomes, which then undergoes a second invagination to form multivesicular bodies (MVBs) containing intraluminal vesicles (ILVs).…”