炎症因子风暴对老年小鼠感染免疫应答的影响
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(1. 复旦大学附属公共卫生临床中心,上海 201508;2. 复旦大学生物医学研究院,上海 200032)

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R-33

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Effect of a cytokine storm on immune responses against viral infection in aged mice
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(1. Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China;2. Institutes of Biomedical Sciences, Fudan University, Shanghai 200032)

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    摘要:

    目的 高致病性禽流感感染小鼠后,肺内检测出过量表达的炎症因子,即炎症因子风暴?老年感染者体内更加常见高水平的炎症应答?本文探讨了炎症风暴对老年宿主肺内抗感染免疫应答的影响?方法 采用老年小鼠(18 ~24 月龄)以流感病毒H9N2 攻毒,建立了老年小鼠感染模型?对照组为H9N2 感染的成年小鼠(6 ~8 周)?分别定量分析了H9N2 感染的老年小鼠肺原位和外周血中炎症因子的表达,并在感染的急性期内,收集的小鼠肺组织,分别制备成切片和消化为单细胞悬液?其中,肺组织切片用于免疫组化原位定量分析免疫细胞分布;从细胞悬液中分选出T 细胞,进行染色计数?结果 与成年小鼠相比,老年小鼠感染H9N2 病毒后,体重下降显著,生存率仅为50%?但是,与成年小鼠感染后肺组织很少检出炎症因子相比,老年小鼠肺内出现炎症因子风暴,炎症因子IL-6 和趋化因子MCP-1 异常高表达,且在感染后第2 天达到峰值(超过4000 pg/ mL),是成年对照小鼠的100 ~1000 倍?老年小鼠感染H9N2 病毒后,与成年对照相比,其肺巨噬细胞应答更低,肺中性粒细胞的迁徙能力更弱,感染后第3 ~7 天内更多地滞留在肺内?此外,老年小鼠感染H9N2 后第7 天,肺内CD8 + T 细胞数量显著下降,CD4 + T 细胞数量与比例则维持正常?结论 老年小鼠感染H9N2 病毒后肺组织出现炎症因子风暴?参与抗感染免疫应答的细胞种类虽然与成年小鼠无显著差异,但是免疫细胞的迁徙能力降低,参与应答的获得性细胞免疫强度也显著降低?

    Abstract:

    Objective A cytokine storm occurs during infection by highly pathogenic viruses such as avian influenza virus. Higher levels of inflammatory responses are more commonly observed in the elderly, associated with worse clinical outcomes. In this study, we investigated the effect of inflammatory responses on the immune response against viral infection in the lung of aged mice. Methods Aged mice (18 -24 months old) were infected with influenza virus H9N2 to establish an infection model. Adult mice (6 - 8 weeks old) were used as the control. After infection, we quantitatively analyzed the expression of inflammatory cytokines in the lung and periphery blood. During the acute infection, murine lung tissues were collected and subjected to in situ analysis of the distribution of recruited immune cells by immunohistochemistry, and pulmonary T cells were counted among digested single cells of lung tissue. Results Compared with the adult mice infected with H9N2, aged mice showed significant weight loss and a low survival rate of 50%.Inflammatory cytokines were rarely detected in the infected adult mice, but were highly detected in the lungs of aged mice.Among them, IL-6 and chemokine MCP-1 were significantly high, which reached peaks of more than 4000 pg/ mL and were 100 - 1000 times higher than those in the adult control mice at day 2 post-infection. Additionally, the pulmonary macrophage response and migration of neutrophils were weaker. On day 7 post-infection, the number of CD8 + T cells decreased significantly in the aged lung, while the number and proportion of CD4 + T cells remained normal. Conclusions An inflammatory cytokine storm is found in the lung of aged mice infected with low pathogenic influenza virus H9N2.Compared with adult mice, the migration ability of immune cells is decreased, and the acquired cellular immunity intensity is reduced significantly.

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袁松华,何涌泉,徐建青,张晓燕.炎症因子风暴对老年小鼠感染免疫应答的影响[J].中国比较医学杂志,2018,28(12):1~8.

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  • 收稿日期:2018-04-26
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  • 在线发布日期: 2019-01-08
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