AUTHOR=Yang Jing , Wu Jin'en , Fu Yong , Yan Lujun , Li Yating , Guo Xiaola , Zhang Yong'e , Wang Xiaoqiang , Shen Yujuan , Cho William C. , Zheng Yadong TITLE=Identification of Different Extracellular Vesicles in the Hydatid Fluid of Echinococcus granulosus and Immunomodulatory Effects of 110 K EVs on Sheep PBMCs JOURNAL=Frontiers in Immunology VOLUME=Volume 12 - 2021 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.602717 DOI=10.3389/fimmu.2021.602717 ISSN=1664-3224 ABSTRACT=Echinococcosis is one of the 17 neglected tropical diseases, being mainly caused by Echinococcus granulosus. Extracellular vesicles (EVs) play an essential role in the host-parasite interplay. However, the EVs in the hydatid fluid (HF) of E. granulosus are not fully characterized. Herein, three different types of HF EVs, designated as 2 K, 10 K and 110 K EVs based on centrifugal force used, were morphologically identified. A total of 133, 110 and 937 proteins were identified in 2 K, 10 K and 110 K EVs, respectively, 11 of which were commonly shared. Moreover, 11, 8 and 25 miRNAs were detected, respectively, and all of 7 selected miRNAs were validated by qPCR to be significantly lower abundant than that in protoscoleces. It was further showed that 110 K EVs were internalized by sheep peripheral blood mononuclear cells (PBMCs) in a time-dependent manner, and induced IL-10, TNF-α and IRF5 to be significantly upregulated and IL-1β, IL-17 and CD14 to be significantly downregulated (p < 0.05). These data demonstrate the physical discrepancy of three HF EVs and an immunomodulatory effect of 110 K EVs on sheep PMBCs, suggesting a role in immune responses during E. granulosus infection.