Pivotal Advance: Invariant NKT cells reduce accumulation of inflammatory monocytes in the lungs and decrease immune-pathology during severe influenza A virus infection
Pivotal Advance: Invariant NKT cells reduce accumulation of inflammatory monocytes in the lungs and decrease immune-pathology during severe influenza A virus infection
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DOI：
10.1189/jlb.0411184
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发表时间：
2012-03-01
影响因子：
5.5
通讯作者：
Ho, Ling-Pei
中科院分区：
文献类型：
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作者：
Kok, Wai Ling;Denney, Laura;Ho, Ling-Pei
在严重的甲型流感病毒（IAV）感染期间，如何调节肺部的强烈免疫反应以最大限度地减少组织损伤，目前还知之甚少。在这里，使用致死性，高致病性IAV感染的模型，我们首先表明，Ly 6C（hi）Ly 6 G（-）炎性单核细胞，而不是中性粒细胞，是WT小鼠肺中的主要浸润。缺乏iNKT细胞的小鼠（J alpha 18（-/-）小鼠）具有增加的炎性单核细胞水平，其与增加的肺损伤和死亡率（但不是病毒载量）相关。iNKT细胞的活化与MCP-1水平的降低和结局的改善相关。iNKT细胞能够在体外以CD 1d依赖性过程选择性裂解感染的产生MCP-1的单核细胞。我们的研究提供了在严重IAV感染期间肺部先天免疫细胞的详细概况和动力学，突出了炎性单核细胞作为主要浸润物，并确定了iNKT细胞在控制这些细胞和肺部免疫病理学中的作用。J.利瓦克91：357-368; 2012.
Little is known of how a strong immune response in the lungs is regulated to minimize tissue injury during severe influenza A virus (IAV) infection. Here, using a model of lethal, high-pathogenicity IAV infection, we first show that Ly6C(hi)Ly6G(-)inflammatory monocytes, and not neutrophils, are the main infiltrate in lungs of WT mice. Mice devoid of iNKT cells (J alpha 18(-/-) mice) have increased levels of inflammatory monocytes, which correlated with increased lung injury and mortality (but not viral load). Activation of iNKT cells correlated with reduction of MCP-1 levels and improved outcome. iNKT cells were able to selectively lyse infected, MCP-1-producing monocytes in vitro, in a CD1d-dependent process. Our study provides a detailed profile and kinetics of innate immune cells in the lungs during severe IAV infection, highlighting inflammatory monocytes as the major infiltrate and identifying a role for iNKT cells in control of these cells and lung immune-pathology. J. Leukoc. Biol. 91: 357-368; 2012.