Structural and functional characterization of Extracellular Vesicles from different yeast strains

Extracellular vesicles (EVs) are lipid-bilayered particles released by cells from all the domains of life for multiple functions, exerted both intra- and inter-kingdom. In fungi, functions of EVs include modulation of the host immune system, which is currently hypothesised to be mediated by the interaction between host immune cells and small RNAs transported by EVs. Most of the studies on fungal EVs immunomodulation so far have been conducted in the context of fungal infections. In order to assess the immune properties of EVs produced by human-associated and non-pathogenic species, we isolated strains of Saccharomyces cerevisiae and Pichia fermentans either from Tuscany grapes or fermented milk, and characterised their EVs in terms of physical properties. Then, immunomodulation abilities of isolated EVs have been studied in vitro through immune assays after internalisation from human monocyte-derived dendritic cells. Results showed a significant reduction of antigen presentation activity of dendritic cells treated with EVs produced by fermented milk strains. Moreover, we sequenced and analysed the small RNA fraction of EVs, founding a large majority of yeast mRNA molecules enriched in functions with no correlation with RNA-mediated regulation mechanisms. In conclusion, this study suggests that one of the mechanisms behind the anti-inflammatory effects of fermented beverages is based on the release of EVs from their yeast strains, and that it doesn't involve RNA regulation of the host cells.