Unveiling the intricate dance: mechanisms underlying liver parasitism of Echinococcus granulosus mediated by protoscoleces-derived small extracellular vesicles

Long-term liver infection represents a conserved parasitism of E. granulosus in the intermediate hosts. However, little is known about hepatic responses mediated by protoscoleces-derived small extracellular vesicles (PSC-sEV). Here, we comprehensively elucidated the characteristics and composition of distinct life stages of E. granulosus. Further, we unveiled differential target capacities, diverse regulatory roles, and neglected pathogenic properties of PSC-sEV, which displayed a key mediator contributing to pathogenesis of hepatic cystic echinococcosis. By utilizing single-cell RNA-seq, we identified heterogeneity in the cell subpopulations (endothelial cells, myeloid cells, NK and T cells) regulated by PSC-sEV during liver CE infection. Finally, we proposed a potential mechanism for achieving parasite-host communication through selective internalization of PSC-sEV in target cells and manipulation of cellular functions via miRNA-TF-mRNA networks. Our work underscores intercellular crosstalk landscapes of PSC-sEV and host cells, highlighting the necessity of targeting PSC for therapeutic intervention and the potential of PSC-sEV as a biomarker for PSC formation.