Extracellular Vesicles From Schistosoma mansoni Adult Worms Stimulate IL‐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.