趋化因子CCL8在广州管圆线虫-宿主适应性中的作用及其机制研究

Angiostrongylus cantonensis invasion primarily cause heavy or negligible eosinophic meningitis and meningoencephalitis in the brain of non-permissive and permissive hosts, respectively. Chemokines are effective leukocyte chemoattractants and may play an essential role in mediating eosinophil recruitment in angiostrongyliasis. In our previous study, genome-scale investigation of permissive hosts (rat and hamster) and non-permissive hosts (mouse and human) for Angiostrongylus cantonensis (AC) firstly revealed CCL8, a non-permissive host-specific eosinophil chemotactic chemokine, with an extremely high-level expression in CNS of AC infected mice. Researches on distinct features of CCL8 may help us understand the molecular events and mechanism of eosinophilic meningitis in angiostrongyliasis. In the present study, the biotechnics including RNAi, knock-out mouse, Dual-Luciferase Reporter Array, microarray chip, fixed microinjection and point mutation were proposed to investigate the molecular mechanism of CCL8 on Angiostrongylus cantonensis-host adaption. In summary, a deletion of CCL8 contributes to larvae migration from brain to lung and adult development of A. cantonensis in permissive hosts and determines host- A. cantonensis adaption, which demonstrates a novel potential drug and (or) a diagnostic target for angiostrongyliasis and enriches a comprehensive understanding of host-parasite co-evolution.

广州管圆线虫病是严重损伤中枢神经系统的新发食源性寄生虫病，广州管圆线虫感染也是迄今已知可引起嗜酸性粒细胞增多性脑膜脑炎或脑膜炎的最常见感染性病因。虫体感染适宜宿主、非适宜宿主可致宿主截然不同病理结局且虫体移行、发育状况迥异。广州管圆线虫-宿主适应性的分子机制仍是广州管圆线虫病防治研究亟需回答的核心科学问题。我们利用基因芯片、单抗阻断及脑部显微定位注射等技术首次证实：广州管圆线虫感染后，非适宜宿主特异性基因—趋化因子CCL8随感染进程极显著上调，是决定广州管圆线虫-宿主适应性的关键因子。本项目拟进一步采用基因敲除动物、芯片检测、RNAi、双荧光素酶报告系统等技术深入研究CCL8在广州管圆线虫感染所致适宜宿主、非适宜宿主不同病理结局中作用的信号通路，全面阐述CCL8在广州管圆线虫-宿主适应性中趋化嗜酸性粒细胞的分子机制，并为确定CCL8或（及）其受体作为广州管圆线虫病防治的新靶标提供科学依据。

广州管圆线虫病是严重损伤中枢神经系统的新发食源性寄生虫病，广州管圆线虫感染也是迄今已知可引起嗜酸性粒细胞增多性脑膜脑炎或脑膜炎的最常见感染性病因。虫体感染适宜宿主、非适宜宿主可致宿主截然不同病理结局且虫体移行、发育状况迥异。广州管圆线虫-宿主适应性的分子机制仍是广州管圆线虫病防治研究亟需回答的核心科学问题。 我们利用基因敲除动物、芯片检测、RNAi、双荧光素酶报告系统等技术确证CCL8是决定广州管圆线虫-宿主寄生适应性的关键分子，并研究了广州管圆线虫感染所致适宜宿主、非适宜宿主不同病理结局中作用的的分子机制，为确定CCL8或（及）其受体作为广州管圆线虫病防治的新靶标提供科学依据。