Wang Lifu, Li Zhitao, Shen Jia, Liu Zhen, Liang Jinyi, Wu Xiaoying, Sun Xi, Wu Zhongdao
Key Laboratory of Tropical Diseases and Control of the Ministry of Education, Sun Yat-sen University, Guangzhou, China.
Parasitol Res. 2015 May;114(5):1865-73. doi: 10.1007/s00436-015-4373-7. Epub 2015 Feb 19.
Exosomes are 30-100-nm membrane vesicles of endocytic origin that are released into the extracellular space upon fusion of the multi-vesicular bodies (MVB) with the plasma membrane, while initial studies described that the role of exosomes was a reticulocyte cargo-disposal mechanism allowing remodeling of the plasma membrane during the maturation of reticulocytes to erythrocytes. Recent studies indicate that exosomes are secreted by most cells and pathogens and play an important role in intercellular signaling and exert regulatory function by carrying bioactive molecules. As numerous pathogens, adult worm of Schistosoma japonicum (S. japonicum) reside in mesenteric veins of definitive host including man and mammal animals. It was reported that the worms or the eggs also have specialized secretion systems to export effector proteins or other molecules into host target cells. However, the mechanisms involved remained unclear. This study investigated the isolation of the exosome-like vesicles secreted by S. japonicum adult worms and its immune activity on microphage in vitro. In this report, we identified exosome-based secretion as a new mechanism for protein secretion by S. japonicum. Electron microscopy tomography revealed the previously unidentified ultrastructural detail of exosome-like vesicles with high resolution; they were found to be typical spherical shape and to have a diverse population that varies in size of 30-100 nm. Exosome-like vesicles isolated from S. japonicum contained a significantly different protein compared with debris pelleted and the apoptosis body. We also demonstrate that macrophages were preferentially differentiated into the M1 subtype while being treated with S. japonicum exosome-like vesicles. This study reveals there are exosome-like vesicles derived by S. japonicum adult worms, and the exosome-like vesicles can mediate M1-type immune- activity of macrophage.
外泌体是30-100纳米的内吞起源膜泡，当多泡体（MVB）与质膜融合时释放到细胞外空间，而最初的研究表明外泌体的作用是一种网织红细胞货物处理机制，可在网织红细胞成熟为红细胞的过程中重塑质膜。最近的研究表明，外泌体由大多数细胞和病原体分泌，在细胞间信号传导中起重要作用，并通过携带生物活性分子发挥调节功能。作为众多病原体之一，日本血吸虫成虫寄生于包括人和哺乳动物在内的终宿主的肠系膜静脉中。据报道，这些蠕虫或虫卵也有专门的分泌系统，可将效应蛋白或其他分子输出到宿主靶细胞中。然而，其中涉及的机制仍不清楚。本研究调查了日本血吸虫成虫分泌的外泌体样囊泡的分离及其对体外巨噬细胞的免疫活性。在本报告中，我们确定基于外泌体的分泌是日本血吸虫蛋白质分泌的一种新机制。电子显微镜断层扫描以高分辨率揭示了外泌体样囊泡以前未被识别的超微结构细节；发现它们是典型的球形，并且有不同大小的群体，大小在30-100纳米之间。从日本血吸虫中分离的外泌体样囊泡与沉淀的碎片和凋亡小体相比，所含蛋白质有显著差异。我们还证明，在用日本血吸虫外泌体样囊泡处理时，巨噬细胞优先分化为M1亚型。本研究揭示了日本血吸虫成虫产生的外泌体样囊泡，并且这些外泌体样囊泡可以介导巨噬细胞的M1型免疫活性。
