Identification of Different Extracellular Vesicles in the Hydatid Fluid of Echinococcus granulosus and Immunomodulatory Effects of 110 K EVs on Sheep PBMCs.

Jing Yang,Xiaoqiang Wang,Yujuan Shen,Jin'En Wu,William C Cho,Yong'E Zhang,Lujun Yan,Xiaola Guo,Yadong Zheng,Yong Fu,Yating Li

doi:10.3389/fimmu.2021.602717

Abstract

Echinococcosis, mainly caused by Echinococcus granulosus, is one of the 17 neglected tropical diseases. 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 the centrifugal force used, were morphologically identified. A total of 97, 80, and 581 proteins were identified in 2 K, 10 K, and 110 K EVs, respectively, 39 of which were commonly shared. Moreover, 11, 8, and 25 miRNAs were detected, respectively, and all of the 7 selected miRNAs were validated by qPCR to be significantly lower abundant than that in protoscoleces. It was further deemed that 110 K EVs were internalized by sheep peripheral blood mononuclear cells (PBMCs) in a time-dependent manner and thus induced interleukin (IL)-10, tumor necrosis factor-α (TNF-α), and IRF5 were significantly upregulated and IL-1β, IL-17, and CD14 were 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.

Highlights

Echinococcosis, caused by the larval stage of the genus Echinococcus, is listed as one of the neglected tropical diseases by WHO [1, 2]
Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the proteins of 10 K and 110 K Extracellular vesicles (EVs) were predominantly involved in metabolic pathways, up to ∼12 and 15% of annotated proteins, respectively (Figure 3B)
The results showed that 110 K EVs induced the significant upregulation of IL-10 and tumor necrosis factor-α (TNF-α) (p < 0.05) in treated sheep peripheral blood mononuclear cells (PBMCs), with IL-17 and IL-1β being significantly downregulated 24 h after treatment (p < 0.05, Figure 6A)

Summary

Introduction

Echinococcosis, caused by the larval stage of the genus Echinococcus, is listed as one of the neglected tropical diseases by WHO [1, 2]. E. granulosus and E. multilocularis are of major public health impact globally and are responsible for cystic. When a natural intermediate host incidentally ingests the food or water contaminated by the eggs, oncospheres hatch in the stomach and intestine and, pass through the portal and lymphatic vessels to reach the liver, lungs, and other organs through bloodstream circulation. They grow into unilocular cysts (metacestodes or hydatid cysts), which are filled with the hydatid fluid (HF) with a lot of protoscoleces. If a definitive host consumes infected organs or offal, the larva develops into the adult in the intestine and, completes its life cycle [3, 9, 13]

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Results

Conclusion