title: Regulatory effects of Echinococcus multilocularis extracellular vesicles on RAW264.7 macrophages.
abstract: 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 34nm to 95nm 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 70kDa, 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.
authors.affiliation: State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, CAAS, Lanzhou 730046, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China. Electronic address: zhengyadong@caas.cn.
authors.forename: Yadong
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, CAAS, Lanzhou 730046, China.
authors.forename: Xiaola
authors.initials: X
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, CAAS, Lanzhou 730046, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Su
authors.affiliation: State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, CAAS, Lanzhou 730046, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
authors.forename: Aijiang
authors.initials: A
authors.lastname: Guo
authors.affiliation: College of Life Science and Technology, Xinjiang University, Urumqi 830046, China.
authors.forename: Juntao
authors.initials: J
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, CAAS, Lanzhou 730046, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Xiang
authors.affiliation: State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, CAAS, Lanzhou 730046, China.
authors.forename: Xiaoan
authors.initials: X
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, CAAS, Lanzhou 730046, China.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Pathobiology, Faculty of Veterinary Sciences, Bahauddin Zakariya University, Multan 60800, Pakistan.
authors.forename: Mazhar
authors.initials: M
authors.lastname: Ayaz
authors.affiliation: State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, CAAS, Lanzhou 730046, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
authors.forename: Xuenong
authors.initials: X
authors.lastname: Luo
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation; D004443:Echinococcosis / Q000469:parasitology*; D048210:Echinococcus multilocularis / Q000502:physiology*; D000067128:Extracellular Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D005786:Gene Expression Regulation; D006790:Host-Parasite Interactions; D008264:Macrophages / Q000378:metabolism / Q000469:parasitology*; D051379:Mice; D008811:Mice, Inbred DBA; D046529:Microscopy, Electron, Transmission; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D000067996:RAW 264.7 Cells; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D016207:Cytokines; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II
keywords: Echinococcus multilocularis; Extracellular vesicle; Macrophage