Mint3/Apba3 depletion ameliorates severe murine influenza pneumonia and macrophage cytokine production in response to the influenza virus.
Mint3/Apba3 depletion ameliorates severe murine influenza pneumonia and macrophage cytokine production in response to the influenza virus.
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DOI：
10.1038/srep37815
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发表时间：
2016-11-24
影响因子：
4.6
通讯作者：
Sakamoto T
中科院分区：
文献类型：
--
作者：
Uematsu T;Fujita T;Nakaoka HJ;Hara T;Kobayashi N;Murakami Y;Seiki M;Sakamoto T
流感病毒(IFV)感染是严重肺炎的常见原因。研究表明，包括巨噬细胞在内的宿主免疫系统的过度激活是IFV感染所介导的严重病理变化的原因。在这里，我们聚焦于X11蛋白家族成员Mint3/Apba3，它通过激活巨噬细胞中的低氧诱导因子-1(HIF-1)，通过糖酵解促进ATP的产生，并探讨其在肺发病和IFV感染的抗病毒防御中的作用。Mint3基因缺陷的小鼠表现出流感肺炎的改善，炎症细胞因子/趋化因子水平减少，中性粒细胞在IFV感染的肺中渗透，而病毒载量、I型干扰素产生或获得性免疫没有改变。在巨噬细胞中，Mint3的缺失分别通过增加IκBα和激活细胞能量传感器AMPK而减弱了针对IFV感染的NF-AMPB信号和由此产生的细胞因子/趋化因子的产生。因此，Mint3可能通过抑制巨噬细胞细胞因子/趋化因子的产生，在不影响宿主抗病毒防御的情况下，成为治疗重症流感肺炎的可能靶点之一。
Influenza virus (IFV) infection is a common cause of severe pneumonia. Studies have suggested that excessive activation of the host immune system including macrophages is responsible for the severe pathologies mediated by IFV infection. Here, we focused on the X11 protein family member Mint3/Apba3, known to promote ATP production via glycolysis by activating hypoxia inducible factor-1 (HIF-1) in macrophages, and examined its roles in lung pathogenesis and anti-viral defence upon IFV infection. Mint3-deficient mice exhibited improved influenza pneumonia with reduced inflammatory cytokines/chemokine levels and neutrophil infiltration in the IFV-infected lungs without alteration in viral burden, type-I interferon production, or acquired immunity. In macrophages, Mint3 depletion attenuated NF-κB signalling and the resultant cytokine/chemokine production in response to IFV infection by increasing IκBα and activating the cellular energy sensor AMPK, respectively. Thus, Mint3 might represent one of the likely therapeutic targets for the treatment of severe influenza pneumonia without affecting host anti-viral defence through suppressing macrophage cytokine/chemokine production.
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影响因子：
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通讯作者：
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影响因子：
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