Inflammasome recognition of influenza virus is essential for adaptive immune responses.
Inflammasome recognition of influenza virus is essential for adaptive immune responses.
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DOI：
10.1084/jem.20081667
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发表时间：
2009-01-16
影响因子：
15.3
通讯作者：
Iwasaki, Akiko
中科院分区：
文献类型：
--
作者：
Ichinohe, Takeshi;Lee, Heung Kyu;Ogura, Yasunori;Flavell, Richard;Iwasaki, Akiko
先天免疫系统通过Toll样受体（TLR）7和视黄酸诱导基因I识别流感病毒感染。这两种识别途径导致I型干扰素的激活和对感染的抵抗。此外，TLR信号是CD 4 T细胞和IgG 2a而不是细胞毒性T淋巴细胞对流感病毒感染的应答所需的。相反，NOD样受体（NLR）在病毒识别和诱导对流感病毒的适应性免疫中的作用尚不清楚。我们证明，呼吸道感染流感病毒的结果在肺中的NLR炎性小体的激活。虽然NLRP 3是某些细胞类型中炎性小体激活所必需的，但CD 4和CD 8 T细胞应答以及粘膜伊加分泌和全身IgG应答需要ASC和胱天蛋白酶-1，而不需要NLRP 3。因此，针对流感攻击的保护性免疫需要ASC、caspase-1和IL-1 R，而不是NLRP 3。此外，我们表明，半胱天冬酶-1炎症体激活造血，而不是基质，隔室需要诱导保护性抗病毒免疫。这些结果表明，除了TLR途径外，ASC炎性体在针对流感病毒的适应性免疫中发挥核心作用。
Influenza virus infection is recognized by the innate immune system through Toll like receptor (TLR) 7 and retinoic acid inducible gene I. These two recognition pathways lead to the activation of type I interferons and resistance to infection. In addition, TLR signals are required for the CD4 T cell and IgG2a, but not cytotoxic T lymphocyte, responses to influenza virus infection. In contrast, the role of NOD-like receptors (NLRs) in viral recognition and induction of adaptive immunity to influenza virus is unknown. We demonstrate that respiratory infection with influenza virus results in the activation of NLR inflammasomes in the lung. Although NLRP3 was required for inflammasome activation in certain cell types, CD4 and CD8 T cell responses, as well as mucosal IgA secretion and systemic IgG responses, required ASC and caspase-1 but not NLRP3. Consequently, ASC, caspase-1, and IL-1R, but not NLRP3, were required for protective immunity against flu challenge. Furthermore, we show that caspase-1 inflammasome activation in the hematopoietic, but not stromal, compartment was required to induce protective antiviral immunity. These results demonstrate that in addition to the TLR pathways, ASC inflammasomes play a central role in adaptive immunity to influenza virus.
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通讯作者：
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通讯作者：
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影响因子：
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作者：
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