Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan 2nd Road, Guangzhou 510080 Guangdong Province, People's Republic of China.
Parasitol Res. 2013 Jul;112(7):2689-95. doi: 10.1007/s00436-013-3436-x. Epub 2013 May 24.
Angiostrongylus cantonensis is an emerging zoonotic pathogen that has caused hundreds of cases of human angiostrongyliasis worldwide. The larva in nonpermissive hosts cannot develop into an adult worm and can cause eosinophilic meningitis and ocular angiostrongyliasis. The mechanism of brain inflammation caused by the worm remains poorly defined. According to previous data of GeneChip, Ym1 in the brain of mice 21 days after infection with A. cantonensis was highly upregulated to over 7,300 times than the untreated mice. Ym1 is an eosinophilic chemotactic factor with the alternative names of chitinase-3-like protein 3, eosinophil chemotactic cytokine, and ECF-L. Ym1 displays chemotactic activity for T lymphocytes, bone marrow cells, and eosinophils and may favor inflammatory responses induced by parasitic infections and allergy. It has been reported that Ym1 is synthesized and secreted by activated macrophages during parasitic infection (Chang et al., J Biol Chem 276(20):17497-17506, 2001). In the brain, microglia are alternatively activated macrophage-derived cells which are the key immune cells in central nervous system inflammation. To explore the role of Ym1 in inflammation caused by A. cantonensis-infected mice, we examined the levels of Ym1 in the sera and cerebrospinal fluid (CSF) of the infected animals, followed by detection of the mRNA expression level of Ym1 in various organs including the brain, lung, liver, spleen, and kidney and of the cytokines IL-5 and IL-13 in the brain of the infected mice with or without intraperitoneal injection of minocycline (an inhibitor of microglial activation) by real-time reserve transcription PCR. Furthermore, immunolocalization of Ym1 in the brains of the infected mice was observed by using a fluorescence microscope. Our results showed that Ym1 was most highly expressed in the brains and CSF of the infected mice along with the process of inflammation. The antibody localized Ym1 to the microglia in the brain of the mice in both infection and minocycline + infection groups. And as in the brain, the mRNA level of Ym1 changed more obviously than IL-5 and IL-13. The study implies that Ym1 might serve as an alternative potential pathological marker which is detected not only in the sera and CSF but also in the brains of the infected mice and Ym1 secreted by microglia might be involved in eosinophilic meningitis and meningoencephalitis caused by A. cantonensis infection.
广州管圆线虫是一种新兴的人畜共患病原体，已在全球范围内导致数百例人体血管圆线虫病。非允许宿主中的幼虫不能发育成成虫，并可引起嗜酸性粒细胞性脑膜炎和眼血管圆线虫病。虫体引起脑炎症的机制尚不清楚。根据之前的 GeneChip 数据，感染广州管圆线虫后 21 天的小鼠脑中的 Ym1 高度上调，超过未处理小鼠的 7300 倍。Ym1 是一种嗜酸性粒细胞趋化因子，其别名有几丁质酶 3 样蛋白 3、嗜酸性粒细胞趋化细胞因子和 ECF-L。Ym1 对 T 淋巴细胞、骨髓细胞和嗜酸性粒细胞具有趋化活性，可能有利于寄生虫感染和过敏引起的炎症反应。据报道，在寄生虫感染期间，Ym1 由激活的巨噬细胞合成和分泌（Chang 等人，J Biol Chem 276(20):17497-17506, 2001）。在大脑中，小胶质细胞是由巨噬细胞衍生的替代性激活细胞，是中枢神经系统炎症中的关键免疫细胞。为了探讨 Ym1 在广州管圆线虫感染小鼠引起的炎症中的作用，我们检测了感染动物血清和脑脊液（CSF）中的 Ym1 水平，然后通过实时定量 RT-PCR 检测了感染小鼠各种器官（包括脑、肺、肝、脾和肾）中 Ym1 的 mRNA 表达水平，以及感染小鼠脑内的细胞因子 IL-5 和 IL-13。此外，我们还通过荧光显微镜观察了感染小鼠脑中 Ym1 的免疫定位。结果表明，随着炎症的发生，Ym1 在感染小鼠的大脑和 CSF 中表达最高。抗体将 Ym1 定位于感染和米诺环素+感染组小鼠大脑中的小胶质细胞。与大脑一样，Ym1 的 mRNA 水平变化比 IL-5 和 IL-13 更明显。该研究表明，Ym1 可能作为一种替代的潜在病理标志物，不仅在感染小鼠的血清和 CSF 中检测到，而且在感染小鼠的大脑中也检测到，由小胶质细胞分泌的 Ym1 可能参与了广州管圆线虫感染引起的嗜酸性粒细胞性脑膜炎和脑膜脑炎。
