p38MAPK guards the integrity of endosomal compartments through regulating necrotic death.
p38MAPK guards the integrity of endosomal compartments through regulating necrotic death.
复制标题
p38mapk通过调节坏死死亡来保护内体室的完整性。
DOI：
10.1038/s41598-022-20786-4
复制
发表时间：
2022-09-29
影响因子：
4.6
通讯作者：
Shayakhmetov, Dmitry M.
中科院分区：
文献类型：
--
作者：
Yao, Jia;Atasheva, Svetlana;Toy, Randall;Blanchard, Emmeline L.;Santangelo, Philip J.;Roy, Krishnendu;Mocarski, Edward S.;Shayakhmetov, Dmitry M.
病原体触发先天免疫系统传感器的激活，启动分子信号，使适当的宿主防御程序。尽管免疫系统的特殊受体对病原体特异性部分或PAMPs的识别已经被很好地定义为许多病原体，但对病原体诱导的宿主细胞功能扰动的感知机制仍然知之甚少。本研究表明，细菌或完全合成的纳米颗粒破坏巨噬细胞内体区室可激活应激反应p38MAPK激酶，从而触发坏死型细胞死亡。p38mapk介导的坏死发生在凋亡诱导caspase- 1和-11、凋亡caspase-8和凋亡诱导受体相互作用蛋白激酶3 （RIPK3）的复合纯合缺失的细胞中，这表明所有这些主要的细胞死亡介质对于p38mapk诱导的内核体破裂的坏死都是必不可少的。p38mapk介导的坏死受到受体相互作用蛋白激酶1 RIPK1的抑制，RIPK1的降解使巨噬细胞致坏死死亡。由于病原体诱导的坏死型细胞死亡与宿主防御感染有关，我们的研究结果表明，宿主细胞的功能扰动被感知为先天免疫系统的一个组成部分。
Pathogens trigger activation of sensors of the innate immune system that initiate molecular signaling enabling appropriate host defense programs. Although recognition of pathogen-specific moieties or PAMPs by specialized receptors of the immune system is well defined for a great number of pathogens, the mechanisms of sensing of pathogen-induced functional perturbations to the host cell remain poorly understood. Here we show that the disruption of endosomal compartments in macrophages by a bacterium or fully synthetic nanoparticles activates stress-response p38MAPK kinase, which triggers execution of cell death of a necrotic type. p38MAPK-mediated necrosis occurs in cells with a compound homozygous deletion of pyroptosis-inducing caspases-1 and -11, apoptotic caspase-8, and necroptosis-inducing receptor-interacting protein kinase-3 (RIPK3), indicating that all of these principal cell death mediators are dispensable for p38MAPK-induced necrosis in response to endosome rupture. p38MAPK-mediated necrosis is suppressed by the receptor-interacting protein kinase 1, RIPK1, and degradation of RIPK1 sensitizes macrophages to necrotic death. Since pathogen-induced cell death of necrotic types is implicated in host defense against infection, our results indicate that functional perturbations in host cells are sensed as a component of the innate immune system.
登录
查看更多内容
影响因子：
56.9
作者：
Ge, BX;Gram, H;Han, JH
通讯作者：
Han, JH
影响因子：
4.8
作者：
Kaiser, William J.;Sridharan, Haripriya;Mocarski, Edward S.
通讯作者：
Mocarski, Edward S.
在细胞死亡和炎症的串扰中进行了编程坏死。
影响因子：
29.7
作者：
Chan FK;Luz NF;Moriwaki K
通讯作者：
Moriwaki K
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
DOI：
10.1084/jem.20170550
发表时间：
2017-08-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kesavardhana S;Kuriakose T;Guy CS;Samir P;Malireddi RKS;Mishra A;Kanneganti TD
通讯作者：
Kanneganti TD