NLRC4 inflammasome-dependent cell death occurs by a complementary series of three death pathways and determines lethality in mice.
NLRC4 inflammasome-dependent cell death occurs by a complementary series of three death pathways and determines lethality in mice.
复制标题
DOI：
10.1126/sciadv.abi9471
复制
发表时间：
2021-10-22
期刊：
影响因子：
13.6
通讯作者：
Han J
中科院分区：
文献类型：
--
作者：
Zhang P;Liu Y;Hu L;Huang K;Hong M;Wang Y;Fan X;Ulevitch RJ;Han J
由NLRC 4炎性体过度激活引起的细胞死亡在小鼠的致死结果中起决定性作用。炎性小体是一种先天性免疫防御机制，但其过度激活可导致宿主死亡。在这里，我们表明，细胞死亡决定了NLRC 4炎性小体过度激活引起的小鼠死亡。NLRC 4依赖性细胞死亡的三条途径按特定顺序相互补充：需要caspase-1和GSDMD的Pyroptosis途径是默认途径;其损伤启动ASC介导的caspase-8依赖性凋亡;当这两条途径被阻断时，caspase-1触发内在凋亡途径。阻断这些死亡途径中的一个或两个会抑制各种细胞因子和脂质介质的诱导，但小鼠仍然会死亡，只有阻断所有死亡途径的基因缺失才能防止NLRC 4介导的细胞死亡，组织损伤和小鼠死亡。此外，通过阻断这些死亡途径，非繁殖性沙门氏菌感染引起的小鼠死亡得以减轻。因此，为了降低感染相关疾病的致死率，当受感染病原体的繁殖被其他手段控制时，防止细胞死亡可能是必要的。
The death of cells elicited by NLRC4 inflammasome overactivation plays a decisive role in lethal outcome of the mice. Inflammasome is an innate immune defense mechanism, but its overactivation can lead to host death. Here, we show that cell death dictates mouse death caused by NLRC4 inflammasome overactivation. To execute NLRC4-dependent cell death, three death pathways complement each other in a specific order: Pyroptosis pathway requiring caspase-1 and GSDMD is the default path; impairment of it initiates ASC-mediated caspase-8–dependent apoptosis; when these two pathways are blocked, caspase-1 triggers intrinsic apoptotic pathway. Blocking one or two of these death pathways inhibits induction of various cytokines and lipid mediators, but mice still succumb, and only genetic deletions that block all death paths prevent NLRC4-mediated cell death, tissue damage, and mice death. In addition, infection of nonpropagative Salmonella-caused mice death is attenuated by blocking these death pathways. Thus, to reduce the lethality of infection-related diseases, preventing cell death might be necessary when propagation of infected pathogen was controlled by other means.
登录
查看更多内容
影响因子：
6.7
作者：
Mascarenhas DPA;Cerqueira DM;Pereira MSF;Castanheira FVS;Fernandes TD;Manin GZ;Cunha LD;Zamboni DS
通讯作者：
Zamboni DS
DOI：
10.1128/genomea.01591-16
发表时间：
2017-02-02
期刊：
Genome announcements
影响因子：
--
作者：
Johnson SA;Ormsby MJ;Wall DM
通讯作者：
Wall DM
影响因子：
4.8
作者：
Jiang, XJ;Wang, XD
通讯作者：
Wang, XD
影响因子：
64.8
作者：
Ding, Jingjin;Wang, Kun;Shao, Feng
通讯作者：
Shao, Feng
影响因子：
6.7
作者：
Levinsohn JL;Newman ZL;Hellmich KA;Fattah R;Getz MA;Liu S;Sastalla I;Leppla SH;Moayeri M
通讯作者：
Moayeri M