cGAS and Ifi204 cooperate to produce type I IFNs in response to Francisella infection.
cGAS and Ifi204 cooperate to produce type I IFNs in response to Francisella infection.
复制标题
DOI：
10.4049/jimmunol.1402764
复制
发表时间：
2015-04-01
期刊：
影响因子：
--
通讯作者：
Monack DM
中科院分区：
文献类型：
--
作者：
Storek KM;Gertsvolf NA;Ohlson MB;Monack DM
I型干扰素（IFN）的产生是针对病毒和细菌感染的重要宿主免疫应答。然而，很少有人知道的配体和相应的宿主受体，触发I型干扰素的生产过程中细菌感染。我们使用了一个模型的细胞内病原体，新杀弗朗西丝菌开始表征I型干扰素对细菌病原体的反应。F. novicida在宿主细胞的胞质溶胶中复制，并激发一种强有力的I型IFN应答，该应答在很大程度上是TLR非依赖性的，但依赖于接头分子STING，这表明在F.杀线虫感染是胞浆性的。在这项研究中，我们报告说，细胞溶质DNA传感器，cGAS和Ifi204，都是需要的STING依赖性I型干扰素响应F。原代和永生化鼠巨噬细胞中的杀线虫感染。我们在RAW 264.7巨噬细胞中创建了cGAS、Ifi204和Sting功能敲除，并证明了cGAS和Ifi204协同感测dsDNA并激活STING依赖性I型IFN途径。此外，我们还发现F. novicida是一种重要的I型IFN刺激配体。cGAS-STING信号传导的一个结果是响应于F.杀线虫感染。而AIM 2炎性小体在F. novicida感染时，通过STING和IRF3的I型IFN信号传导在F.杀线虫感染。总的来说，我们的研究表明cGAS和Ifi204协同感测胞质dsDNA和F. novicida感染产生强烈的I型IFN应答。
Type I interferon (IFN) production is an important host immune response against viral and bacterial infections. However, little is known about the ligands and corresponding host receptors that trigger type I IFN production during bacterial infections. We used a model intracellular pathogen, Francisella novicida to begin characterizing the type I IFN response to bacterial pathogens. F. novicida replicates in the cytosol of host cells and elicits a robust type I IFN response that is largely TLR-independent, but is dependent on the adapter molecule STING, suggesting that the type I IFN stimulus during F. novicida infection is cytosolic. In this study, we report that the cytosolic DNA sensors, cGAS and Ifi204, are both required for the STING-dependent type I IFN response to F. novicida infection in both primary and immortalized murine macrophages. We created cGAS, Ifi204 and Sting functional knockouts in RAW264.7 macrophages and demonstrated that cGAS and Ifi204 cooperate to sense dsDNA and activate the STING-dependent type I IFN pathway. Additionally, we showed that dsDNA from F. novicida is an important type I IFN stimulating ligand. One outcome of cGAS-STING signaling is the activation of the AIM2 inflammasome in response to F. novicida infection. While the AIM2 inflammasome is beneficial to the host during F. novicida infection, type I IFN signaling by STING and IRF3 is detrimental to the host during F. novicida infection. Collectively, our studies indicate that cGAS and Ifi204 cooperate to sense cytosolic dsDNA and F. novicida infection to produce a strong type I IFN response.
登录
查看更多内容
DOI：
10.1126/science.1244040
发表时间：
2013-09-20
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Li XD;Wu J;Gao D;Wang H;Sun L;Chen ZJ
通讯作者：
Chen ZJ
影响因子：
30.5
作者：
Buerckstuemmer, Tilmann;Baumann, Christoph;Superti-Furga, Giulio
通讯作者：
Superti-Furga, Giulio
影响因子：
11.4
作者：
Hansen, Kathrine;Prabakaran, Thaneas;Paludan, Soren R.
通讯作者：
Paludan, Soren R.
DOI：
10.4049/jimmunol.1100088
发表时间：
2011-09-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jin L;Hill KK;Filak H;Mogan J;Knowles H;Zhang B;Perraud AL;Cambier JC;Lenz LL
通讯作者：
Lenz LL
DOI：
10.1126/science.1232033
发表时间：
2013-02-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Mali P;Yang L;Esvelt KM;Aach J;Guell M;DiCarlo JE;Norville JE;Church GM
通讯作者：
Church GM