Extracellular vesicles derived from Spirometra erinaceieuropaei plerocercoids inhibit activation of murine macrophage RAW264.7 cells
Extracellular vesicles derived from Spirometra erinaceieuropaei plerocercoids inhibit activation of murine macrophage RAW264.7 cells
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猴头螺旋体来源的细胞外囊泡抑制小鼠巨噬细胞RAW264.7细胞的活化
DOI：
10.1016/j.parint.2023.102742
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发表时间：
2023
影响因子：
1.9
通讯作者：
Otsuki Hitoshi
中科院分区：
文献类型：
--
作者：
Kondo Yoko;Ito Daisuke;Taniguchi Rika;Tademoto Sayuri;Horie Takashi;Otsuki Hitoshi
寄生蠕虫通过改变宿主的免疫反应来促进长期寄生。我们先前从螺旋虫的排泄/分泌产物中分离纯化了一种糖蛋白，即质球蛋白免疫抑制因子(P-ISF)，并报道了它的基因序列。在本研究中，我们从OFS的排泄/分泌产物中分离出细胞外小泡(EVS)。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以及肿瘤坏死因子-α、白介素1β和白介素6的基因表达。EVS是直径50-250纳米的膜结合囊泡，定位于脊椎动物的全身。来自脊椎动物的EV包裹着各种未知的蛋白质和microRNAs(MiRNAs)，这些蛋白质和microRNAs是非编码RNA，在转录后基因调控中发挥重要作用。对EVS的miRNAs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。总共鉴定了26个不同的miRNA家族，包括miR-71、miR-10-5p、miR-223和let-7-5p，这些家族已经被报道具有免疫抑制作用。我们用抗P-ISF抗体进行免疫印迹，证实P-ISF存在于上清液中，但在EVS中没有。这些结果表明这就是问题所在。刺参神经毒素通过释放P-ISF和EVS抑制宿主免疫。
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 Spirometraerinaceieuropaeiplerocercoids and reported its cDNA and genomic DNA sequences. In this study, we isolated extracellular vesicles (EVs) from the excretory/secretory products ofS. erinaceieuropaeiplerocercoids 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 thatS. erinaceieuropaeiplerocercoids suppress host immunity by releasing P-ISF and EVs.