{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:08:00Z","timestamp":1792804080867,"version":"4.5.0"},"reference-count":32,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,14]],"date-time":"2022-10-14T00:00:00Z","timestamp":1665705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82072307"],"award-info":[{"award-number":["82072307"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81772224"],"award-info":[{"award-number":["81772224"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971969"],"award-info":[{"award-number":["81971969"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272369"],"award-info":[{"award-number":["82272369"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["NHCKFKT2021-08"],"award-info":[{"award-number":["NHCKFKT2021-08"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the NHC Key Laboratory of Parasite","award":["82072307"],"award-info":[{"award-number":["82072307"]}]},{"name":"the NHC Key Laboratory of Parasite","award":["81772224"],"award-info":[{"award-number":["81772224"]}]},{"name":"the NHC Key Laboratory of Parasite","award":["81971969"],"award-info":[{"award-number":["81971969"]}]},{"name":"the NHC Key Laboratory of Parasite","award":["82272369"],"award-info":[{"award-number":["82272369"]}]},{"name":"the NHC Key Laboratory of Parasite","award":["NHCKFKT2021-08"],"award-info":[{"award-number":["NHCKFKT2021-08"]}]},{"name":"Vector Biology (National Institute of Parasitic Diseases, Chinese Center for Diseases Control and Prevention)","award":["82072307"],"award-info":[{"award-number":["82072307"]}],"id":[{"id":"https:\/\/ror.org\/04wktzw65","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Vector Biology (National Institute of Parasitic Diseases, Chinese Center for Diseases Control and Prevention)","award":["81772224"],"award-info":[{"award-number":["81772224"]}],"id":[{"id":"https:\/\/ror.org\/04wktzw65","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Vector Biology (National Institute of Parasitic Diseases, Chinese Center for Diseases Control and Prevention)","award":["81971969"],"award-info":[{"award-number":["81971969"]}],"id":[{"id":"https:\/\/ror.org\/04wktzw65","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Vector Biology (National Institute of Parasitic Diseases, Chinese Center for Diseases Control and Prevention)","award":["82272369"],"award-info":[{"award-number":["82272369"]}],"id":[{"id":"https:\/\/ror.org\/04wktzw65","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Vector Biology (National Institute of Parasitic Diseases, Chinese Center for Diseases Control and Prevention)","award":["NHCKFKT2021-08"],"award-info":[{"award-number":["NHCKFKT2021-08"]}],"id":[{"id":"https:\/\/ror.org\/04wktzw65","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Cystic echinococcosis, a major parasitic disease caused by Echinococcus granulosus, seriously threatens human health. The excretory\u2013secretory (ES) products of E. granulosus can induce immune tolerance in dendritic cells (DCs) to downregulate the host\u2019s immune response; however, the effect of exosomes in the ES products on the DCs has remained unclear. This study showed that E. granulosus protoscoleces-derived exosome-like vesicles (PSC-ELVs) could be internalized by bone marrow-derived dendritic cells (BMDCs), allowing for the delivery of the parasite microRNAs to the BMDCs. Moreover, PSC-ELVs induced BMDCs to produce the proinflammatory cytokinesinterleukin (IL)-6, IL-12, IL-\u03b2, tumor necrosis factor-alpha (TNF-\u03b1), and interferon-gamma (IFN-\u03b3). PSC-ELVs also upregulated the BMDCs surface marker major histocompatibility complex class II (MHC II), as well as costimulatory molecules CD40, CD80, and CD86. PSC-ELV-derived egr-miR-277a-3p upregulated the IL-6, IL-12, and TNF-\u03b1 mRNA levels in BMDCs. Moreover, egr-miR-277a-3p directly targeted Nfkb1 (encoding nuclear factor kappa B 1) to significantly suppress the mRNA and protein levels of NF-\u03baB1 in BMDCs, while the expression of NF-\u03baB p65 significantly increased, suggesting that egr-miR-277a-3p induces the production of proinflammatory cytokines by the modification of the NF-kB p65\/p50 ratio in BMDCs. These results demonstrated that PSC-ELVs and egr-miR-277a-3p might enhance DCs maturation and differentiation in a cross-species manner, which in turn may modulate the host immune responses and offer a new approach to echinococcosis prevention and treatment.<\/jats:p>","DOI":"10.3390\/cells11203220","type":"journal-article","created":{"date-parts":[[2022,10,16]],"date-time":"2022-10-16T21:10:10Z","timestamp":1665954610000},"page":"3220","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Echinococcus granulosus Protoscoleces-Derived Exosome-like Vesicles and Egr-miR-277a-3p Promote Dendritic Cell Maturation and Differentiation"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9410-4438","authenticated-orcid":false,"given":"Xiaofan","family":"Zhang","sequence":"first","affiliation":[{"name":"National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, (Chinese Center for Tropical Diseases Research), Key Laboratory of Parasite and Vector Biology, National Health Commission of the People\u2019s Republic of China, World Health Organization Collaborating Centre for Tropical Diseases, Shanghai 200025, China"},{"name":"Department of Laboratory Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenci","family":"Gong","sequence":"additional","affiliation":[{"name":"National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, (Chinese Center for Tropical Diseases Research), Key Laboratory of Parasite and Vector Biology, National Health Commission of the People\u2019s Republic of China, World Health Organization Collaborating Centre for Tropical Diseases, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaohui","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huixia","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Parasite Control, Qinghai Province Institute for Endemic Diseases Prevention and Control, Xining 811602, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4386-6624","authenticated-orcid":false,"given":"Yujuan","family":"Shen","sequence":"additional","affiliation":[{"name":"National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, (Chinese Center for Tropical Diseases Research), Key Laboratory of Parasite and Vector Biology, National Health Commission of the People\u2019s Republic of China, World Health Organization Collaborating Centre for Tropical Diseases, Shanghai 200025, China"},{"name":"The School of Global Health, Chinese Center for Tropical Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1974-0047","authenticated-orcid":false,"given":"Jianping","family":"Cao","sequence":"additional","affiliation":[{"name":"National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, (Chinese Center for Tropical Diseases Research), Key Laboratory of Parasite and Vector Biology, National Health Commission of the People\u2019s Republic of China, World Health Organization Collaborating Centre for Tropical Diseases, Shanghai 200025, China"},{"name":"The School of Global Health, Chinese Center for Tropical Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e3866","DOI":"10.1136\/bmj.e3866","article-title":"Diagnosis, treatment, and management of echinococcosis","volume":"344","author":"McManus","year":"2012","journal-title":"BMJ"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Pan, W., Zhou, H.J., Shen, Y.J., Wang, Y., Xu, Y.X., Hu, Y., Jiang, Y.Y., Yuan, Z.Y., Ugwu, C.E., and Cao, J.P. (2013). Surveillance on the status of immune cells after Echinnococcus granulosus protoscoleces infection in Balb\/c mice. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0059746"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s13071-016-1350-7","article-title":"Echinococcus granulosus Antigen B binds to monocytes and macrophages modulating cell response to inflammation","volume":"9","author":"Folle","year":"2016","journal-title":"Parasites Vectors"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s13071-020-3919-4","article-title":"Arginase promotes immune evasion of Echinococcus granulosus in mice","volume":"13","author":"Cao","year":"2020","journal-title":"Parasites Vectors"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Mourglia-Ettlin, G., Marques, J.M., Chabalgoity, J.A., and Dematteis, S. (2011). Early peritoneal immune response during Echinococcus granulosus establishment displays a biphasic behavior. PLoS Negl. Trop. Dis., 5.","DOI":"10.1371\/journal.pntd.0001293"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1128\/IAI.01156-06","article-title":"Echinococcus granulosus antigen B impairs human dendritic cell differentiation and polarizes immature dendritic cell maturation towards a Th2 cell response","volume":"75","author":"Rigano","year":"2007","journal-title":"Infect. Immun."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Wang, Y., Zhou, H., Shen, Y., Wang, Y., Wu, W., Liu, H., Yuan, Z., Xu, Y., Hu, Y., and Cao, J. (2015). Impairment of dendritic cell function and induction of CD4+CD2+Foxp3+ T cells by excretory-secretory products: A potential mechanism of immune evasion adopted by Echinococcus granulosus. BMC Immunol., 16.","DOI":"10.1186\/s12865-015-0110-3"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Sun, X.M., Guo, K., Hao, C.Y., Zhan, B., Huang, J.J., and Zhu, X. (2019). Trichinella spiralis excretory-secretory products stimulate host regulatory T cell differentiation through activating dendritic cells. Cells, 8.","DOI":"10.3390\/cells8111404"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s00018-017-2595-9","article-title":"Current knowledge on exosome biogenesis and release","volume":"75","author":"Hessvik","year":"2018","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.pt.2015.06.009","article-title":"Exosomes and other extracellular vesicles: The new communicators in parasite infections","volume":"31","author":"Coakley","year":"2015","journal-title":"Trends Parasitol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1126\/science.1243175","article-title":"Molecular biology. Is there social RNA?","volume":"341","author":"Sarkies","year":"2013","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.jhep.2019.10.029","article-title":"A schistosome miRNA promotes host hepatic fibrosis by targeting transforming growth factor beta receptor III","volume":"72","author":"He","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"101","DOI":"10.3389\/fcimb.2020.00101","article-title":"A microrna derived from Schistosoma Japonicum promotes schistosomiasis hepatic fibrosis by targeting host secreted frizzled-related protein 1","volume":"10","author":"Wang","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"274","DOI":"10.3389\/fimmu.2012.00274","article-title":"Regulatory dendritic cells: There is more than just immune activation","volume":"3","author":"Schmidt","year":"2012","journal-title":"Front. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.lfs.2019.01.005","article-title":"Phenotypical and functional evaluation of dendritic cells after exosomal delivery of miRNA-155","volume":"219","author":"Asadirad","year":"2019","journal-title":"Life Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"9417","DOI":"10.1002\/jcp.27626","article-title":"microRNA modified tumor-derived exosomes as novel tools for maturation of dendritic cells","volume":"234","author":"Taghikhani","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Nicolao, M.C., Rodriguez Rodrigues, C., and Cumino, A.C. (2019). Extracellular vesicles from Echinococcus granulosus larval stage: Isolation, characterization and uptake by dendritic cells. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007032"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.vetpar.2017.01.022","article-title":"Isolation and characterization of exosomes derived from fertile sheep hydatid cysts","volume":"236","author":"Gonzalez","year":"2017","journal-title":"Vet. Parasitol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"316","DOI":"10.3389\/fcimb.2020.00316","article-title":"Comprehensive analysis of non-coding rna profiles of exosome-like vesicles from the protoscoleces and hydatid cyst fluid of Echinococcus granulosus","volume":"10","author":"Zhang","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"779770","DOI":"10.3389\/fimmu.2022.779770","article-title":"MicroRNA-5112 targets iKKgamma to dampen the inflammatory response and improve clinical symptoms in both bacterial infection and DSS-induced colitis","volume":"13","author":"Kang","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/1479-5876-9-9","article-title":"Human saliva, plasma and breast milk exosomes contain RNA: Uptake by macrophages","volume":"9","author":"Lasser","year":"2011","journal-title":"J. Transl. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e12969","DOI":"10.1111\/cmi.12969","article-title":"Characterisation of infection associated microRNA and protein cargo in extracellular vesicles of Theileria annulata infected leukocytes","volume":"21","author":"Gillan","year":"2019","journal-title":"Cell. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Silva-Gomez, J.A., Galicia-Moreno, M., Sandoval-Rodriguez, A., Miranda-Roblero, H.O., Lucano-Landeros, S., Santos, A., Monroy-Ramirez, H.C., and Armendariz-Borunda, J. (2021). Hepatocarcinogenesis prevention by pirfenidone is ppargamma mediated and involves modification of nuclear NF-kB p65\/p50 ratio. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111360"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5564","DOI":"10.1093\/nar\/gkx146","article-title":"Structural characterization of interactions between transactivation domain 1 of the p65 subunit of NF-\u03baB and transcription regulatory factors","volume":"45","author":"Lecoq","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1182\/blood-2011-02-338004","article-title":"Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes","volume":"119","author":"Montecalvo","year":"2012","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3187","DOI":"10.2147\/JIR.S365217","article-title":"Tfh exosomes derived from allergic rhinitis promote dc maturation through miR-142-5p\/CDK5\/STAT3 pathway","volume":"15","author":"Teng","year":"2022","journal-title":"J. Inflamm. Res."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Benites, B.D., Alvarez, M.C., and Saad, S.T.O. (2019). Small Particles, Big Effects: The Interplay between exosomes and dendritic cells in antitumor immunity and immunotherapy. Cells, 8.","DOI":"10.3390\/cells8121648"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Pan, W., Xu, H.W., Hao, W.T., Sun, F.F., Qin, Y.F., Hao, S.S., Liu, H., Cao, J.P., Shen, Y.J., and Zheng, K.Y. (2018). The excretory-secretory products of Echinococcus granulosus protoscoleces stimulated IL-10 production in B cells via TLR-2 signaling. BMC Immunol., 19.","DOI":"10.1186\/s12865-018-0267-7"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1186\/s13071-017-2263-9","article-title":"The excretory-secretory products of Echinococcus granulosus protoscoleces directly regulate the differentiation of B10, B17 and Th17 cells","volume":"10","author":"Pan","year":"2017","journal-title":"Parasites Vectors"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7154","DOI":"10.4049\/jimmunol.174.11.7154","article-title":"Dendritic cell-intrinsic expression of NF-kappa B1 is required to promote optimal Th2 cell differentiation","volume":"174","author":"Artis","year":"2005","journal-title":"J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Courtois, G., and Fauvarque, M.O. (2018). The many roles of ubiquitin in NF-kappaB signaling. Biomedicines, 6.","DOI":"10.3390\/biomedicines6020043"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/20\/3220\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:53:53Z","timestamp":1760144033000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/20\/3220"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,14]]},"references-count":32,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["cells11203220"],"URL":"https:\/\/doi.org\/10.3390\/cells11203220","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,14]]}}}