Shroom2基因缺陷对日本血吸虫感染影响的初步研究  

Preliminary study on the impact of Shroom2 gene deficiency on Schistosoma japonicum infection

作　　者：刘婉玲 修磊 胡薇 张文宏[1] 吴晶 LIU Wanling;XIU Lei;HU Wei;ZHANG Wenhong;WU Jing(Department of Infectious Diseases,Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response,National Medical Center for Infectious Diseases,Huashan Hospital,Fudan University,Shanghai,200040,China;School of Life Sciences,Fudan University,Shanghai 200438,China)

机构地区：[1]复旦大学附属华山医院感染科,国家传染病医学中心,上海200400 [2]复旦大学生命科学院,上海200441

出　　处：《微生物与感染》2024年第4期219-226,共8页Journal of Microbes and Infections

基　　金：国家自然科学基金(31972699);上海市卫健委加强公共卫生体系建设三年行动计划重点学科建设项目(GWVI-11.1-07)。

摘　　要：SHROOM2是一种肌动蛋白结合蛋白,参与细胞运动调节和肌动蛋白细胞骨架重塑。而日本血吸虫虫卵可引发肉芽肿形成,在虫卵周围形成有组织的免疫聚集体。本研究偶然发现,Shroom2缺失的小鼠在感染血吸虫后,其死亡率远高于野生型小鼠,故本研究旨在研究Shroom2基因敲除小鼠在感染日本血吸虫后的病程进展,以揭示Shroom2基因在血吸虫感染和宿主应对虫卵肉芽肿形成免疫反应中的潜在作用。本文利用CRISPR/Cas9技术构建了Shroom2基因敲除小鼠,采用腹部贴片法将日本血吸虫尾蚴分别感染C57BL/6野生型(WT)和Shroom2基因敲除小鼠(KO),每只小鼠感染30±2条。感染后每日监测小鼠状态,记录死亡数量,并在感染第5、7周将小鼠安乐死,取其外周血进行血常规分析;苏木素-伊红染色观察肝组织的病理变化。结果显示,Shroom2基因敲除小鼠在感染血吸虫后的急性期内死亡率显著提高,并伴有肝脏严重病理变化和血常规指标异常。这表明Shroom2基因在调节宿主免疫反应中起关键作用,其缺失可能导致宿主对病原体的易感性增加,从而加速疾病进程。SHROOM2 is an actin-binding protein involved in the regulation of cell motility and actin cytoskeleton remodeling.Schistosome eggs can induce granuloma formation,leading to organized immune aggregates around the eggs.This study unexpectedly observed that Shroom2-deficient mice exhibited a significantly higher mortality rate after infection with Schistosoma japonicum compared to wild-type mice.This study aimed to investigate the disease progression in Shroom2 knockout mice after infection with Schistosoma japonicum,revealing the potential role of the Shroom2 gene in the immune response to schistosome infection and granuloma formation around the eggs.It used CRISPR/Cas9 technology to generate Shroom2 knockout(KO)mice.Both C57BL/6 wild-type(WT)and KO mice were infected with Schistosoma japonicum cercariae(30±2 cercariae/mouse)via abdominal skin exposure.The mice were monitored daily,and the number of deaths was recorded.At the fifth and the seventh weeks post-infection,mice were sacrificed for blood routine analysis and liver histopathology with hematoxylin-eosin(HE)staining.KO mice showed a significant increase in mortality during the acute phase of schistosome infection,accompanied by severe liver pathology and abnormal blood parameters.These findings suggest that the Shroom2 gene plays a critical role in regulating the host immune response,and its deficiency may increase susceptibility to pathogens,accelerating disease progression.

关 键 词：Shroom2 免疫缺陷 日本血吸虫 

分 类 号：R38[医药卫生—医学寄生虫学] R392[医药卫生—基础医学]