IRGB10 Liberates Bacterial Ligands for Sensing by the AIM2 and Caspase-11-NLRP3 Inflammasomes.
IRGB10 Liberates Bacterial Ligands for Sensing by the AIM2 and Caspase-11-NLRP3 Inflammasomes.
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DOI：
10.1016/j.cell.2016.09.012
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发表时间：
2016-10-06
期刊：
影响因子：
64.5
通讯作者：
Kanneganti, Thirumala-Devi
中科院分区：
文献类型：
--
作者：
Man, Si Ming;Karki, Rajendra;Sasai, Miwa;Place, David E.;Kesavardhana, Sannula;Temirov, Jamshid;Frase, Sharon;Zhu, Qifan;Malireddi, R. K. Subbarao;Kuriakose, Teneema;Peters, Jennifer L.;Neale, Geoffrey;Brown, Scott A.;Yamamoto, Masahiro;Kanneganti, Thirumala-Devi
炎性小体是一种细胞内信号传导复合物，其在识别病原体和生理异常时驱动半胱天冬酶-1的活化、焦亡以及促炎细胞因子IL-1β和IL-18的释放。细菌配体必须确保进入细胞质以激活炎性小体，然而，隐藏的配体在细胞质中释放的机制仍不清楚。在这里，我们表明，干扰素诱导蛋白IRGB 10是必要的DNA敏感AIM 2炎性体的激活由Francisella novicida，并有助于激活的LPS敏感caspase-11和NLRP 3炎性体的革兰氏阴性菌。IRGB 10通过需要鸟苷酸结合蛋白的机制直接靶向细胞质细菌。IRGB 10在细菌细胞膜上的定位损害了细菌结构的完整性，并介导了用于炎性体传感器识别的配体的胞质释放。总的来说，我们的研究结果揭示了IRGB 10作为细胞自主免疫和先天免疫传感途径之间界面上保守信号中枢的一部分。找到通往细胞质的途径：一种干扰素诱导蛋白定位于细菌的细胞膜，损害其结构完整性并介导释放配体，否则无法通过炎性小体进行传感。
The inflammasome is an intracellular signaling complex, which on recognition of pathogens and physiological aberration, drives activation of caspase-1, pyroptosis, and the release of the pro-inflammatory cytokines IL-1β and IL-18. Bacterial ligands must secure entry into the cytoplasm to activate inflammasomes, however, the mechanism by which concealed ligands are liberated in the cytoplasm have remained unclear. Here, we showed that the interferon-inducible protein IRGB10 is essential for activation of the DNA-sensing AIM2 inflammasome by Francisella novicida, and contributed to the activation of the LPS-sensing caspase-11 and NLRP3 inflammasome by Gram-negative bacteria. IRGB10 directly targeted cytoplasmic bacteria through a mechanism requiring guanylate-binding proteins. Localization of IRGB10 to the bacterial cell membrane compromised bacterial structural integrity and mediated cytosolic release of ligands for recognition by inflammasome sensors. Overall, our results reveal IRGB10 as part of a conserved signaling hub at the interface between cell-autonomous immunity and innate immune sensing pathways. Finding the route to the cytoplasm: an interferon-inducible protein localizes to the cell membrane of bacteria, compromising its structural integrity and mediating release of ligands, otherwise inaccessible, for sensing by inflammasomes.
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影响因子：
3.4
作者：
Khaminets A;Hunn JP;Könen-Waisman S;Zhao YO;Preukschat D;Coers J;Boyle JP;Ong YC;Boothroyd JC;Reichmann G;Howard JC
通讯作者：
Howard JC
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：
5.8
作者：
Gautier, Romain;Douguet, Dominique;Drin, Guillaume
通讯作者：
Drin, Guillaume
DOI：
10.1126/science.1240988
发表时间：
2013-09-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hagar JA;Powell DA;Aachoui Y;Ernst RK;Miao EA
通讯作者：
Miao EA
影响因子：
14.9
作者：
Dereeper A;Guignon V;Blanc G;Audic S;Buffet S;Chevenet F;Dufayard JF;Guindon S;Lefort V;Lescot M;Claverie JM;Gascuel O
通讯作者：
Gascuel O