Laboratory of Nematology, Plant Sciences Group, Wageningen University and Research, Droevendaalsesteeg 1, 6708 PB, Wageningen, The Netherlands.
Department of Parasitology, Leiden University Medical Center, Albinusdreef, 2333 ZA, Leiden, The Netherlands.
Sci Rep. 2020 Oct 28;10(1):18528. doi: 10.1038/s41598-020-74485-z.
Helminth parasites secrete a wide variety of immunomodulatory proteins and lipids to dampen host immune responses. Many of these immunomodulatory compounds are modified with complex sugar structures (or glycans), which play an important role at the host-parasite interface. As an example, the human blood fluke Schistosoma mansoni produces highly fucosylated glycan structures on glycoproteins and glycolipids. Up to 20 different S. mansoni fucosyltransferase (SmFucT) genes can be found in genome databases, but thus far only one enzyme has been functionally characterized. To unravel the synthesis of highly fucosylated N-glycans by S. mansoni, we examined the ability of ten selected SmFucTs to modify N-glycans upon transient expression in Nicotiana benthamiana plants. All enzymes were localized in the plant Golgi apparatus, which allowed us to identify the SmFucTs involved in core fucosylation and the synthesis of complex antennary glycan motifs. This knowledge provides a starting point for investigations into the role of specific fucosylated glycan motifs of schistosomes in parasite-host interactions. The functionally characterized SmFucTs can also be applied to synthesize complex N-glycan structures on recombinant proteins to study their contribution to immunomodulation. Furthermore, this plant expression system will fuel the development of helminth glycoproteins for pharmaceutical applications or novel anti-helminth vaccines.
寄生虫会分泌多种免疫调节蛋白和脂质，以抑制宿主的免疫反应。其中许多免疫调节化合物都经过复杂的糖结构（或聚糖）修饰，这些结构在宿主-寄生虫界面中起着重要作用。例如，人类血吸虫 Schistosoma mansoni 在糖蛋白和糖脂上产生高度岩藻糖基化的聚糖结构。在基因组数据库中可以找到多达 20 种不同的 S. mansoni 岩藻糖基转移酶（SmFucT）基因，但迄今为止，只有一种酶的功能得到了表征。为了揭示 S. mansoni 高度岩藻糖基化 N-聚糖的合成方式，我们研究了在烟草 Nicotiana benthamiana 植物中转瞬时表达的 10 种选定的 SmFucT 修饰 N-聚糖的能力。所有酶都定位于植物高尔基体中，这使我们能够鉴定出参与核心岩藻糖基化和合成复杂天线聚糖基序的 SmFucT。这一知识为研究血吸虫中特定岩藻糖基化聚糖基序在寄生虫-宿主相互作用中的作用提供了起点。功能表征的 SmFucT 也可用于在重组蛋白上合成复杂的 N-聚糖结构，以研究它们对免疫调节的贡献。此外，这种植物表达系统将为寄生虫糖蛋白的药物应用或新型抗寄生虫疫苗的开发提供动力。
