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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。
Objective To establish a model of nude mice infected with respiratory syncytial virus (RSV) and observe the replication of RSV, the infiltration of airway inflammatory cells, lung injury and airway hyperresponsiveness (AHR ), Which laid the foundation for further exploring the pathogenicity of innate immunity in RSV. Methods Female T cell deficient nude mice (Balb / c background) and normal Balb / c mice (6-8 weeks old) were divided into control group and RSV group. Intranasal inoculation of cell culture supernatant or RSV A2 virus solution was performed. Virus titers; bronchoalveolar lavage fluid perfusion parallel inflammatory cell count and classification of count; some mice take the left lung, HE staining after histopathological score; pulmonary function test by volume mapping; cytokine detection by ELISA. Results The virus clearance in nude mice was delayed than that in Balb / c mice. RSV caused obvious infiltration of inflammatory cells, pathological lung injury and AHR in nude and Balb / c mice for at least 60 days. RSV infection was nude Mice and Balb / c mice, the biphasic changes in cytokines, acute phase of interferon-based, chronic phase Th2-type cytokines mainly. Conclusion The innate immunity independently relies on T cells and independently mediates acute and chronic airway inflammation and AHR associated with RSV. It suggests that the development of RSV vaccine or drug should fully consider the effect of innate immunity.