Department of Parasitology, School of Medicine, China Medical University, Taichung, 404, Taiwan.
Department of Parasitology, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan.
Parasit Vectors. 2020 Jun 18;13(1):317. doi: 10.1186/s13071-020-04189-w.
Angiostrongylus cantonensis is an important food-borne zoonotic parasite. Humans are non-permissive hosts, and this parasite develops into fifth-stage larvae (L5) in the brain and subarachnoid cavity and then induces eosinophilic meningitis and eosinophilic meningoencephalitis. Excretory/secretory products (ESPs) are valuable targets for the investigation of host-parasite interactions. These products contain a wide range of molecules for penetrating defensive barriers and avoiding the immune response of the host. Endoplasmic reticulum (ER) stress has been found to be associated with a wide range of parasitic infections and inflammation. ER stress can increase cell survival via the activation of downstream signalling. However, the mechanisms of ER stress in A. cantonensis infection have not yet been clarified. This study was designed to investigate the molecular mechanisms of ER stress in astrocytes after treatment with the ESPs of A. cantonensis L5.
The results demonstrated that A. cantonensis infection activated astrocytes in the mouse hippocampus and induced the expression of ER stress-related molecules. Next, the data showed that the expression of ER stress-related molecules and the Ca concentration were significantly increased in activated astrocytes after treatment with the ESPs of L5 of A. cantonensis. Ultimately, we found that ESPs induced GRP78 expression via the Sonic hedgehog (Shh) signalling pathway.
These findings suggest that in astrocytes, the ESPs of A. cantonensis L5 induce ER stress and that the Shh signalling pathway plays an important role in this process.
广州管圆线虫是一种重要的食源性人畜共患寄生虫。人类是非适宜宿主，该寄生虫在脑和蛛网膜下腔发育为第五期幼虫（L5），然后诱导嗜酸性脑膜炎和嗜酸性脑膜脑炎。排泄/分泌产物（ESP）是研究宿主-寄生虫相互作用的有价值的靶点。这些产物包含广泛的分子，用于穿透防御屏障并逃避宿主的免疫反应。内质网（ER）应激已被发现与广泛的寄生虫感染和炎症有关。ER 应激可以通过激活下游信号通路来增加细胞存活。然而，ER 应激在广州管圆线虫感染中的机制尚未阐明。本研究旨在探讨 A. cantonensis L5 的 ESP 处理后星形胶质细胞中 ER 应激的分子机制。
结果表明，A. cantonensis 感染激活了小鼠海马中的星形胶质细胞，并诱导了 ER 应激相关分子的表达。接下来，数据显示，在用 A. cantonensis L5 的 ESP 处理后，激活的星形胶质细胞中 ER 应激相关分子的表达和 Ca 浓度显著增加。最终，我们发现 ESP 通过 Sonic hedgehog (Shh) 信号通路诱导 GRP78 表达。
这些发现表明，在星形胶质细胞中，A. cantonensis L5 的 ESP 诱导 ER 应激，Shh 信号通路在此过程中起重要作用。
