FoxO1在小鼠感染流感病毒H1N1中的作用及机制  

Role and mechanism of FoxO1 gene in mouse infection of influenza virus H1N1

作　　者：李佳佳 宫赛赛 何志利 孙娅坤 程洋 袁顺宗 罗德炎 吕树娟[1] 王慧 LI Jiajia;GONG Saisai;HE Zhili;SUN Yakun;CHENG Yang;YUAN Shunzong;LUO Deyan;LYU Shujuan;WANG Hui(School of Basic Medical Science,Anhui Medical University,Hefei 230032,China;State Key Laboratory of Pathogen and Biosecurity,Institute of Microbiology and Epidemiology,Academy of Military Medicine,Academy of Military Sciences,Beijing 100071,China;General Hospital of PLA Fifth Medical Center,Beijing 100071,China)

机构地区：[1]安徽医科大学基础医学院,合肥230032 [2]军事科学院军事医学研究院微生物流行病研究所病原微生物生物安全国家重点实验室,北京100071 [3]中国人民解放军总医院第五医学中心,北京100071

出　　处：《免疫学杂志》2022年第2期145-150,共6页Immunological Journal

基　　金：国家自然科学基金(31870156)。

摘　　要：目的探讨叉头盒转录因子O1(forkhead box O1,FoxO1)在小鼠抵抗流感病毒H1N1感染中发挥的作用及机制。方法用琼脂糖凝胶电泳鉴定小鼠的基因型后,将小鼠分为2组:条件性敲除NKp46^(+)细胞中FoxO1基因的Foxo1^(△NK)组小鼠,以及对照组WT小鼠;2组小鼠使用滴鼻法同1天感染流感病毒H1N1,每天记录小鼠体质量及2组小鼠的死亡情况;在2组小鼠体质量及状态差异明显的第10天取样,HE染色法观察肺组织病理;Luminex液相芯片技术检测肺组织匀浆上清中36种细胞因子的表达情况;流式细胞术检测肺组织免疫细胞的比例变化。结果与WT组相比,感染流感病毒后Foxo1^(△NK)组小鼠死亡率增加,体质量下降更加严重;肺组织病理显示炎症反应减弱;肺组织匀浆上清中的细胞因子表达水平下降,ENA-78、IFN-α、IL-4、IL-5显著降低;肺组织免疫细胞中CD3^(+)NKp46^(+)NKT细胞比例显著下降。结论FoxO1基因的缺失加重了小鼠流感感染进程,可能是通过抑制依赖FoxO1基因调控的CD3^(+)NKp46^(+)NKT细胞相关免疫反应。This study was performed to explore the role and mechanism of the forkhead box transcription factor O1(FoxO1)gene in mice during influenza virus H1N1 infection.Mouse were genotyped using agarose gel electrophoresis and divided Foxo1^(ΔNK)group(mice with the conditional knockout of the FoxO1 gene in NKp46^(+)cells)and control group(WT mice).Both groups were infected with influenza virus H1N1 on the same day by method of nosedrops.Mouse weight and death of both groups were recorded daily;the samples were taken on the 10 th day when the differences was obvious in weight and status between the two groups of mice.Then lung histopathology was observed using HE staining;the expression of 36 cytokines in the lung tissue homogenate was determined by Luminex liquid phase microarray;and the proportion change of immune cells in lung tissue was measured by flow cytometry.Compared with WT group,Foxo1^(ΔNK)group demonstrated higher mortality and more severe weight loss after influenza virus infection.Furthermore,lung histopathology showed a diminished inflammatory response in the Foxo1^(ΔNK)group,the levels of cytokines decreased in the supernatant of lung tissue homogenates,and ENA-78,IFN-α,IL-4,IL-5 were significantly reduced.Also the proportion of CD3^(+)NKp46^(+)NKT cells in lung tissue immune cells decreased significantly in the Foxo1^(ΔNK)group.In summary,deletion of the FoxO1 gene aggravates the progression of influenza infection in mice,probably by inhibiting CD3^(+)NKp46^(+)NKT cell-associated immune responses.

关 键 词：叉头盒转录因子O1 NKT细胞 甲型流感病毒 免疫反应 

分 类 号：R392.12[医药卫生—免疫学]