Extracellular Vesicles From <i>Schistosoma mansoni</i> Adult Worms Stimulate <scp>IL</scp> ‐10 Release by B Cells

Schistosome parasites are known to modulate host immune responses, which is achieved in part through the release of excretory/secretory (ES) products, including extracellular vesicles (EVs). During chronic schistosomiasis, increased regulatory responses are found, which include enhanced IL-10 production by B (Breg) cells. ES products from schistosome eggs are able to induce IL-10 production by B cells. However, since infection with male worms only (without egg production) also promotes IL-10 producing B cells, we here studied the stimulatory effects of adult worm ES and EVs on murine and human B cells. Worm ES increased IL-10 release by mouse splenic B cells; this activity was concentrated in defined size-separated fractions of adult worm ES. Interestingly, mass spectrometry of the fractions that induced the highest IL-10 response revealed an enrichment of EV-associated proteins. Indeed, highly purified adult worm EVs could interact with mouse splenic B cells, visualised by binding of a schistosome-specific tetraspanin (TSP2) targeting antibody. Furthermore, purified adult worm EVs induced IL-10 release in both mouse splenic and human peripheral blood B cells, suggesting that adult worm EVs can play a role in immune regulatory processes within their host.