The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA.
The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA.
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DOI：
10.1016/j.immuni.2009.02.005
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发表时间：
2009-04-17
期刊：
影响因子：
32.4
通讯作者：
Ting, Jenny P. -Y.
中科院分区：
文献类型：
--
作者：
Allen, Irving C.;Scull, Margaret A.;Moore, Chris B.;Holl, Eda K.;McElvania-TeKippe, Erin;Taxman, Debra J.;Guthrie, Elizabeth H.;Pickles, Raymond J.;Ting, Jenny P. -Y.
NLR基因介导宿主对各种致病刺激的免疫。然而，NLR参与病毒感应的体内证据还没有得到广泛的调查，而且仍然存在争议。作为对NLRP3在RNA病毒感染过程中生理作用的最终测试，本工作探索了NLRP3炎症体成分在流感病毒感染过程中的体内作用。缺乏Nlrp3、Asc或Caspase-1而不是NLRC4的小鼠在暴露于流感病毒后表现出显著的死亡率增加但免疫反应降低。利用dsRNA(聚(I：C))和单链RNA(SsRNA40)的类似物，我们证明了NLRP3介导的反应可以被RNA物种激活。从机制上讲，流感病毒对NLRP3炎症体的激活依赖于溶酶体的成熟和活性氧的存在。抑制ROS诱导可消除流感感染过程中动物体内IL-1β的产生。综上所述，这些数据将NLRP3炎症体作为通过感知病毒RNA来抵御流感感染的宿主防御的重要组成部分。
NLR genes mediate host immunity to various pathogenic stimuli. However, in vivo evidence for NLR involvement in viral sensing has not been widely investigated and remains controversial. As an ultimate test of the physiologic role of NLRP3 during RNA viral infection, this work explores the in vivo role of NLRP3 inflammasome components during influenza virus infection. Mice lacking Nlrp3, ASC, or Caspase-1, but not Nlrc4, exhibit dramatically increased mortality but reduced immune response following influenza virus exposure. Utilizing analogs of dsRNA (poly(I:C)) and ssRNA (ssRNA40), we demonstrate that NLRP3-mediated response can be activated by RNA species. Mechanistically, NLRP3 inflammasome activation by influenza virus is dependent upon lysosomal maturation and reactive oxygen species. Inhibition of ROS induction eliminated IL-1β production in animals during influenza infection. Together, these data place the NLRP3 inflammasome as an essential component in host defense against influenza infection through the sensing of viral RNA.
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