Wei Jie, Wu Feng, He Ai, Zeng Xin, Ouyang Li-si, Liu Ming-she, Zheng Huan-qin, Lei Wan-long, Wu Zhong-dao, Lv Zhi-yue
Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
Parasitol Res. 2015 Sep;114(9):3247-54. doi: 10.1007/s00436-015-4541-9. Epub 2015 May 24.
Angiostrongylus cantonensis (A. cantonensis) is a rodent nematode. Adult worms of A. cantonensis live in the pulmonary arteries of rats; humans are non-permissive hosts like the mice. The larva cannot develop into an adult worm and only causes serious eosinophilic meningitis or meningo-encephalitis if humans or mice eat food containing larva of A. cantonensis in the third stage. The differing consequences largely depend on differing immune responses of hosts to parasite during A. cantonensis invasion and development. To further understand the reasons why mice and rats attain different outcomes in A. cantonensis infection, we used the HE staining to observe the pathological changes of infected mice and rats. In addition, we measured mRNA levels of some cytokines (IL-5, IL-6, IL-13, Eotaxin, IL-4, IL-10, TGF-β, IFN-γ, IL-17A, TNF-α, IL-1β, and iNOS) in brain tissues of mice and rats by real-time PCR. The result showed that brain inflammation in mice was more serious than in rats. Meanwhile, mRNA expression levels of IL-6, IL-1β, TNF-α, and iNOS increased after mice were infected. In contrast, mRNA levels of these cytokines in rats brain tissues decreased at post- infection 21 days. These cytokines mostly were secreted by activated microglia in central nervous system. Microglia of mice and rats were showed by Iba-1 (microglia marker) staining. In micee brains, microglia got together and had more significant activation than in rats brains. The results demonstrate that mice and rats have different CNS inflammation after infection by A. cantonensis, and it is in line with other researchers' reported findings. In conclusion, it is suggested that microglia activation is probably to be one of the most important factors in angiostrongyliasis from our study.
广州管圆线虫是一种寄生于啮齿动物的线虫。广州管圆线虫的成虫寄生于大鼠的肺动脉内;人类和小鼠一样都是非适宜宿主。幼虫无法发育为成虫,若人类或小鼠食用了含有三期广州管圆线虫幼虫的食物,只会引发严重的嗜酸性粒细胞性脑膜炎或脑膜脑炎。不同的后果很大程度上取决于宿主在广州管圆线虫入侵和发育过程中对寄生虫的免疫反应不同。为了进一步了解小鼠和大鼠在广州管圆线虫感染中出现不同结果的原因,我们采用苏木精-伊红染色观察感染小鼠和大鼠的病理变化。此外,我们通过实时聚合酶链反应检测小鼠和大鼠脑组织中一些细胞因子(白细胞介素-5、白细胞介素-6、白细胞介素-13、嗜酸性粒细胞趋化因子、白细胞介素-4、白细胞介素-10、转化生长因子-β、干扰素-γ、白细胞介素-17A、肿瘤坏死因子-α、白细胞介素-1β和诱导型一氧化氮合酶)的信使核糖核酸水平。结果显示,小鼠的脑部炎症比大鼠更严重。同时,小鼠感染后白细胞介素-6、白细胞介素-1β、肿瘤坏死因子-α和诱导型一氧化氮合酶的信使核糖核酸表达水平升高。相比之下,大鼠脑组织中这些细胞因子的信使核糖核酸水平在感染后21天下降。这些细胞因子大多由中枢神经系统中活化的小胶质细胞分泌。通过离子钙结合衔接分子-1(小胶质细胞标志物)染色显示小鼠和大鼠的小胶质细胞。在小鼠脑中,小胶质细胞聚集在一起,比大鼠脑中有更明显的活化。结果表明,小鼠和大鼠在感染广州管圆线虫后中枢神经系统炎症不同,这与其他研究人员报道的结果一致。总之,我们的研究表明小胶质细胞活化可能是嗜酸性粒细胞增多性脑膜脑炎最重要的因素之一。