摘要
目的建立呼吸道合胞病毒（respiratory syncytial virus,RSV）感染裸鼠模型,在排除T细胞干扰的情况下,观察RSV的复制情况、气道炎症细胞浸润、肺组织损伤及气道高反应性（AHR）,为进一步探讨固有免疫在RSV中的致病作用奠定基础。方法6~8周雌性T细胞缺陷裸鼠（Balb/c背景）及正常Balb/c小鼠分为对照组及RSV组,分别滴鼻接种细胞培养上清或RSV A2病毒液,空斑实验检测病毒滴度;灌取支气管肺泡灌洗液并行炎症细胞计数及分类计数;部分小鼠取左肺,HE染色后行组织病理评分;肺功能检测用全身体积描技法;细胞因子检测用ELISA法。结果裸鼠中病毒清除较Balb/c小鼠延迟;RSV在裸鼠及Balb/c小鼠中均引起明显的炎症细胞浸润、肺组织病理损伤及AHR,且至少可持续60 d;RSV感染裸鼠及Balb/c小鼠后,细胞因子呈双相变化,急性期以干扰素升高为主,慢性期以Th2类细胞因子升高为主。结论固有免疫可不依赖于T细胞,独立介导RSV相关急慢性期气道炎症及AHR,提示RSV疫苗或药物的开发应充分考虑固有免疫的作用。
To establish a nude mouse model of RSV infection, female nude mice（on a Balb/c background） and normal Balb/c mice at the age of 6-8 weeks were inoculated with cell culture supernatant（control groups） or RSV A2（RSV groups） intranasally. Viral replication, the infiltration of airway inflammatory cells, lung tissue damage and AHR following RSV challenge in the absence of T cells were observed. Plaque assay for RSV viral titer showed that viral clearance was delayed in nude mice in comparison to normal Balb/c mice. RSV caused overt airway inflammation, lung tissue damage as well as AHR in both mice strains, which lasted for at least 60 days. The concentration of the cytokines in BAL（bronchoalveolar lavage） fluid demonstrated diphasic changes of cytokines in both mouse strains following RSV infection： interferons（IFN-α, IFN-β, IFN-γ） were significantly increased in the acute stage while Th2 cytokines（IL-4, IL-5, IL-10） were significantly increased in the later phase of RSV infection.In conclusion, the innate immunity can mediate RSV-associated acute and chronic airway inflammation and AHR without T cells. Thus, innate immunity should be taken into consideration when RSV-targeted vaccines or medicines are developed.
出处
《免疫学杂志》
CAS
CSCD
北大核心
2015年第12期1019-1023,1035,共6页
Immunological Journal
基金
国家自然科学基金(81170010,81470208)
关键词
RSV
裸鼠
病理特征
RSV
Nude mice
Pathological characteristics
