Parasitic helminths modify host immune reactions to promote long-term parasitism. We previously purified a glycoprotein, plerocercoid-immunosuppressive factor (P-ISF), from the excretory/secretory products of Spirometra erinaceieuropaei plerocercoids and reported its cDNA and genomic DNA sequences. In this study, we isolated extracellular vesicles (EVs) from the excretory/secretory products of S. erinaceieuropaei plerocercoids and found that they suppressed the production of nitric oxide and the gene expression of tumor necrosis factor-α, interleukin-1β, and interleukin-6 in lipopolysaccharide-stimulated macrophages. EVs are membrane-bound vesicles 50–250 nm in diameter and are localized in the whole bodies of plerocercoids. EVs from plerocercoids encapsulate a variety of unidentified proteins and microRNAs (miRNAs), which are non-coding RNAs that play essential roles in post-transcriptional gene regulation. The miRNAs of the EVs were analyzed, and 334,137 sequencing reads were mapped to the genomes of other organisms. A total of 26 different miRNA families were identified, including miR-71, miR-10-5p, miR-223, and let-7-5p, which have been reported to have immunosuppressive effects. We confirmed that P-ISF was present in the supernatant but not in the EVs by western blotting with an anti-P-ISF antibody. These results suggest that S. erinaceieuropaei plerocercoids suppress host immunity by releasing P-ISF and EVs.

寄生虫改变宿主免疫反应以促进长期寄生。我们之前从Spirometra erinaceieeuropaei plerocercoids的排泄/分泌产物中纯化了糖蛋白 plerocercoid 免疫抑制因子 (P-ISF)，并报告了其 cDNA 和基因组 DNA 序列。在这项研究中，我们从S. erinaceieeuropaei的排泄/分泌产物中分离出细胞外囊泡 (EV)plerocercoids 并发现它们抑制脂多糖刺激的巨噬细胞中一氧化氮的产生和肿瘤坏死因子-α、白细胞介素-1β 和白细胞介素-6 的基因表达。EV 是直径为 50-250 nm 的膜结合囊泡，位于 plerocercoids 的整个身体中。来自 plerocercoids 的 EV 封装了多种身份不明的蛋白质和 microRNA (miRNA)，它们是非编码 RNA，在转录后基因调控中发挥重要作用。对 EV 的 miRNA 进行了分析，并将 334,137 个测序读数映射到其他生物的基因组。共鉴定出 26 个不同的 miRNA 家族，包括 miR-71、miR-10-5p、miR-223 和 let-7-5p，据报道它们具有免疫抑制作用。我们通过使用抗 P-ISF 抗体的蛋白质印迹法确认 P-ISF 存在于上清液中，但不存在于 EV 中。这些结果表明S. erinaceieuropaei plerocercoids 通过释放 P-ISF 和 EV 来抑制宿主免疫。