Trichinella spiralis secretes stage-specific extracellular vesicles for modulating host microenvironment for parasitism

Extracellular vesicles (EVs) regulate cell-to-cell communication by transferring biomolecules within individuals or between different organisms. Trichinella spiralis is thought to secrete EVs to establish parasitism, but the detailed mechanisms of EV-mediated parasitic strategies have remained unclear. We identified EVs of T. spiralis as stage-specific in adult worms in host intestine (AW-EVs) and larvae in host muscles (ML-EVs). Stage-specific EVs exhibited unique functions, such as suppressing the expression of mucin-related genes only in AW-EVs and inducing genes associated with myoblast differentiation found in nurse cell formation in ML-EVs. Both EVs also suppressed IL-6 expression. These functions corelated with the contents of each EV, as confirmed by proteomics and whole microRNA sequencing. One of the microRNAs common to both EVs, tsp-miR-1, was involved in the suppression of IL-6 expression. These results suggest that Trichinella spiralis secretes stage-specific EVs containing unique as well as common biomolecules to regulate the host microenvironment for parasitism.