BALB/c鼠和裸鼠呼吸道合胞病毒感染比较研究

摘要

目的 比较普通BALB/c鼠和裸鼠呼吸道合胞病毒(RSV)感染免疫及炎症反应特点.方法 BALB/c鼠和裸鼠感染RSV后不同时间空斑形成试验检测肺组织病毒滴度,计数支气管肺泡灌洗液(BALF)白细胞总数和分类,HE染色分析肺组织病理学改变,免疫组化检测肺组织F4/80+细胞和CD49b+细胞.ELISA检测BALF中TNF-α、IFN-r、IL-12和IL-10浓度.结果 BALB/c鼠和裸鼠感染RSV后肺组织病毒滴度在第3天达峰值,感染裸鼠带毒时间更长,在感染后各天病毒滴度明显高于BALB/c鼠(P＜0.05),肺组织病理改变也更重.感染BALB/c鼠和裸鼠BALF白细胞总数明显升高,分类以淋巴细胞为主.感染裸鼠与感染BALB/c鼠比较,肺组织检测到更多的F4/80+巨噬细胞和CD49b+NK细胞(P＜0.05),BALF中TNF-α、IL-12和IL-10水平更高(P＜0.05).结论 RSV感染裸鼠与BALB/c鼠比较,病毒复制水平更高,时间更持久,炎症反应更重.单核巨噬细胞和NK细胞是RSV感染重要的免疫细胞和炎症细胞,炎症反应强度并不一定与T细胞免疫应答平行.%Objective To compare respiratory syncytial virus(RSV)infection and inflammatory responses between immunocompetent BALB/c mice and immanodeficient nude mice.Methods At various time points after BSV infection of BALB/c mice and nude mice,pulmonary viral titers were assayed.Leukocvtes in bronchoalveolar lavage fluid(BALF)and pulmonary histology were identified.F4/80+cells and CD49b+cells in lung tissue were examined by immunohistochemistry,and the cytokines of TNF-α,IL-12,IFN-r and IL-10 in BALF were assayed by ELISA.Results RSV titers in infected BALB/c mice and nude mice peaked on the 3rd day postinoculation,and nude mice had higher-level and more durative viral replication than BALB/c mice.RSV infection induced more severe pulmonary histopathology and larger number of leukocytes in airway in nude mice than in BALB/c mice.RSV infection enhanced more pulmonary F4/80+macrophages,CD49b+ NK cells in both mice.Furthermore infected nude mice had larger amount of pulmonary macrophages and NK cells than infected BALB/c mice.RSV infected BALB/c mice secreted more TNF-α,IL-12,IFN-r and IL-10 as compared with control BALB/c mice,and infected nude mice had hisher level of TNF-α.IL-12 and IL-10 than infected BALB/c mice.Conclusion Nude mice are good model for severe and pemistent RSV infection in immunocomprised hosts.The inflammation induced by RSV infection is not parallel with the immune response of T cells,and macrophages and NK cells are potent immunocytes and inflammatory cells in RSV infection especially when T lymphocytes are absent.