Regulatory effects of Echinococcus multilocularis extracellular vesicles on RAW264.7 macrophages

Extracellular vesicles (EVs) play a role in intercellular communications via exchanging biological molecules, being involved in host-parasite interplay. Little is to date known about E. multilocularis EVs and their biological activities. Here spherical EVs secreted by E. multilocularis metacestodes were shown to range predominately from 34 nm to 95 nm in diameter. A total of 433 proteins were identified in the EVs, and the proteins involved in binding (42%) and catalytic activity (41%) were most frequently represented. Moreover, the proteins associated with EV biogenesis and trafficking, including annexin, 14-3-3, tetraspanin and heat shock protein 70 kDa, were highly enriched. It was shown that the EVs remarkably suppressed NO produced by activated RAW macrophages via downregulation of inducible nitric oxide synthase expression (p < 0.01). Suppression of pro-inflammatory cytokines, especially IL-1α and IL-1β, was also observed post treatment with the EVs. Conversely, increased expression of the majority (10/11) of key components involved in the LPS/TLR4 pathway was induced by the EVs. These results demonstrate a regulatory effect of E. multilocularis EVs on macrophages, suggesting a role in parasite-host interactions.