Intracellular Nucleic Acid Sensing Triggers Necroptosis through Synergistic Type I IFN and TNF Signaling.
Intracellular Nucleic Acid Sensing Triggers Necroptosis through Synergistic Type I IFN and TNF Signaling.
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DOI：
10.4049/jimmunol.1701492
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发表时间：
2018-04-15
期刊：
影响因子：
--
通讯作者：
Oberst A
中科院分区：
文献类型：
--
作者：
Brault M;Olsen TM;Martinez J;Stetson DB;Oberst A
细胞质内病毒核酸的感应对于感染后先天免疫应答的诱导是必不可少的。然而，这种感知发生在已经被感染的细胞内。感染细胞的死亡可以通过消除病毒的复制生态位和促进炎症介质的释放而对宿主有益。在这里，我们表明，通过cGAS-STING或RIG-I-MAVS分别感测细胞内DNA或RNA，导致骨髓源性巨噬细胞中RIPK 3的激活和坏死性凋亡。值得注意的是，这需要通过I型干扰素（IFN）和肿瘤坏死因子（TNF）受体两者的信号传导，揭示了这些途径之间的协同作用以诱导细胞死亡。此外，我们发现小鼠中STING的过度激活导致休克样表型，其死亡率需要坏死性凋亡途径以及IFN和TNF共信号传导的激活，表明坏死性凋亡是体内STING信号传导的结果之一。
The sensing of viral nucleic acids within the cytosol is essential for the induction of innate immune responses following infection. However, this sensing occurs within cells that have already been infected. The death of infected cells can be beneficial to the host by eliminating the virus’s replicative niche and facilitating the release of inflammatory mediators. Here, we show that sensing of intracellular DNA or RNA by cGAS-STING or RIG-I-MAVS, respectively, leads to activation of RIPK3 and necroptosis in bone marrow-derived macrophages. Notably, this requires signaling through both type I interferon (IFN) and tumor necrosis factor (TNF) receptors, revealing synergy between these pathways to induce cell death. Furthermore, we show that hyper-activation of STING in mice leads to a shock-like phenotype, the mortality of which requires activation of the necroptotic pathway and IFN and TNF co-signaling, demonstrating that necroptosis is one outcome of STING signaling in vivo.
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影响因子：
8.8
作者：
Corrales L;Glickman LH;McWhirter SM;Kanne DB;Sivick KE;Katibah GE;Woo SR;Lemmens E;Banda T;Leong JJ;Metchette K;Dubensky TW Jr;Gajewski TF
通讯作者：
Gajewski TF
影响因子：
30.3
作者：
Nogusa S;Thapa RJ;Dillon CP;Liedmann S;Oguin TH 3rd;Ingram JP;Rodriguez DA;Kosoff R;Sharma S;Sturm O;Verbist K;Gough PJ;Bertin J;Hartmann BM;Sealfon SC;Kaiser WJ;Mocarski ES;López CB;Thomas PG;Oberst A;Green DR;Balachandran S
通讯作者：
Balachandran S
影响因子：
32.4
作者：
Gall A;Treuting P;Elkon KB;Loo YM;Gale M Jr;Barber GN;Stetson DB
通讯作者：
Stetson DB
DOI：
10.1038/nri3921
发表时间：
2015-12
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.8
作者：
Kaiser, William J.;Sridharan, Haripriya;Mocarski, Edward S.
通讯作者：
Mocarski, Edward S.