Sterile signals generate weaker and delayed macrophage NLRP3 inflammasome responses relative to microbial signals.
Sterile signals generate weaker and delayed macrophage NLRP3 inflammasome responses relative to microbial signals.
复制标题
DOI：
10.1038/cmi.2016.11
复制
发表时间：
2017-01
影响因子：
24.1
通讯作者：
中科院分区：
文献类型：
--
作者：
炎症是宿主对微生物感染或无菌损伤的反应，其目的是消除损伤，修复组织并恢复稳态。巨噬细胞和NLRP 3炎性体是这两种类型损伤的关键哨兵。虽然已经确定NLRP 3炎性体被无菌损伤期间释放的微生物产物和分子激活，但尚不清楚这些不同类型的信号引起的反应是否不同。在这项研究中，我们分别使用脂多糖和肿瘤坏死因子作为原型微生物和无菌信号1刺激物来引发NLRP 3炎性体。然后，我们分别使用细菌毒素尼日利亚菌素和从坏死细胞释放的常见产物ATP作为原型微生物和无菌信号2刺激物，以触发小鼠和人巨噬细胞中NLRP 3炎性体复合物的组装。我们发现，当信号1和信号2都是无菌的时，NLRP 3炎性小体反应最弱，但当两个信号中至少有一个是微生物时，反应更快更强。最终，当两种信号都是微生物时，引起了最快速和最有效的反应。总之，这些数据表明，微生物与无菌信号在动力学和幅度上都是不同的，它们产生炎性小体依赖性反应的能力。NLRP3对无菌刺激物与微生物刺激物的反应的这种层次结构可能反映了免疫系统对感染的存在快速反应以阻止病原体传播的迫切需要。
Inflammation is the host response to microbial infection or sterile injury that aims to eliminate the insult, repair the tissue and restore homeostasis. Macrophages and the NLRP3 inflammasome are key sentinels for both types of insult. Although it is well established that the NLRP3 inflammasome is activated by microbial products and molecules released during sterile injury, it is unclear whether the responses elicited by these different types of signals are distinct. In this study, we used lipopolysaccharide and tumor necrosis factor as prototypical microbial and sterile signal 1 stimuli, respectively, to prime the NLRP3 inflammasome. We then used the bacterial toxin nigericin and a common product released from necrotic cells, ATP, as prototypical microbial and sterile signal 2 stimuli, respectively, to trigger the assembly of the NLRP3 inflammasome complex in mouse and human macrophages. We found that NLRP3 inflammasome responses were weakest when both signal 1 and signal 2 were sterile, but responses were faster and stronger when at least one of the two signals was microbial. Ultimately, the most rapid and potent responses were elicited when both signals were microbial. Together, these data suggest that microbial versus sterile signals are distinct, both kinetically and in magnitude, in their ability to generate inflammasome-dependent responses. This hierarchy of NLRP3 responses to sterile versus microbial stimuli likely reflects the urgent need for the immune system to respond rapidly to the presence of infection to halt pathogen dissemination.
登录
查看更多内容
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
32.4
作者：
Duong, Bao H.;Onizawa, Michio;Oses-Prieto, Juan A.;Advincula, Rommel;Burlingame, Alma;Malynn, Barbara A.;Ma, Averil
通讯作者：
Ma, Averil
影响因子：
30.5
作者：
通讯作者：
--
DOI：
10.1073/pnas.1320294111
发表时间：
2014-01-14
影响因子：
11.1
作者：
Lin, Keng-Mean;Hu, Wei;Pasare, Chandrashekhar
通讯作者：
Pasare, Chandrashekhar
DOI：
10.4049/jimmunol.0901363
发表时间：
2009-07-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bauernfeind FG;Horvath G;Stutz A;Alnemri ES;MacDonald K;Speert D;Fernandes-Alnemri T;Wu J;Monks BG;Fitzgerald KA;Hornung V;Latz E
通讯作者：
Latz E