TREM2/β-catenin attenuates NLRP3 inflammasome-mediated macrophage pyroptosis to promote bacterial clearance of pyogenic bacteria.
TREM2/β-catenin attenuates NLRP3 inflammasome-mediated macrophage pyroptosis to promote bacterial clearance of pyogenic bacteria.
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DOI：
10.1038/s41419-022-05193-x
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发表时间：
2022-09-06
影响因子：
9
通讯作者：
Wu, Minhao
中科院分区：
文献类型：
--
作者：
Wang, Yi;Cao, Can;Zhu, Yanting;Fan, Huifeng;Liu, Qiaojuan;Liu, Yiting;Chen, Kang;Wu, Yongjian;Liang, Siping;Li, Meiyu;Li, Lexi;Liu, Xi;Zhang, Yuanqing;Wu, Chenglin;Lu, Gen;Wu, Minhao
髓样细胞2上表达的触发受体（TREM2）被认为是保护宿主免受细菌感染的保护因子，但其如何引发这一作用尚不清楚。在本研究中，我们证明骨髓细胞2 （TREM2）上表达的触发受体的缺乏显著增强了四种常见化脓性细菌（包括金黄色葡萄球菌、铜绿假单胞菌、肺炎链球菌和大肠杆菌）诱导的巨噬细胞热亡。TREM2缺乏也降低了巨噬细胞的细菌杀灭率，而Caspase-1或GSDMD抑制则促进了巨噬细胞介导的对这些细菌的清除。进一步研究表明，TREM2对巨噬细胞焦亡和细菌根除的作用主要依赖于NLRP3炎性体的激活状态。此外，作为TREM2的关键下游，β-catenin在Ser675位点被TREM2信号磷酸化，并在细胞核和细胞质中积累。β-catenin通过与ASC相互作用，降低NLRP3表达，抑制炎性小体复合物组装，介导TREM2对NLRP3炎性小体和巨噬细胞焦亡的影响。TREM2/β-catenin共同抑制NLRP3炎性体调节巨噬细胞焦亡，增强巨噬细胞介导的化脓性细菌清除。
Triggering receptors expressed on myeloid cells 2 (TREM2) is considered a protective factor to protect host from bacterial infection, while how it elicits this role is unclear. In the present study, we demonstrate that deficiency of triggering receptors expressed on myeloid cells 2 (TREM2) significantly enhanced macrophage pyroptosis induced by four common pyogenic bacteria including Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae, and Escherichia coli. TREM2 deficiency also decreased bacterial killing ratio of macrophage, while Caspase-1 or GSDMD inhibition promoted macrophage-mediated clearance to these bacteria. Further study demonstrated that the effect of TREM2 on macrophage pyroptosis and bacterial eradication mainly dependents on the activated status of NLRP3 inflammasome. Moreover, as the key downstream of TREM2, β-catenin phosphorylated at Ser675 by TREM2 signal and accumulated in nucleus and cytoplasm. β-catenin mediated the effect of TREM2 on NLRP3 inflammasome and macrophage pyroptosis by reducing NLRP3 expression, and inhibiting inflammasome complex assembly by interacting with ASC. Collectively, TREM2/β-catenin inhibits NLRP3 inflammasome to regulate macrophage pyroptosis, and enhances macrophage-mediated pyogenic bacterial clearance.
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DOI：
10.4049/jimmunol.1102836
发表时间：
2012-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Otero K;Shinohara M;Zhao H;Cella M;Gilfillan S;Colucci A;Faccio R;Ross FP;Teitelbaum SL;Takayanagi H;Colonna M
通讯作者：
Colonna M
影响因子：
28.2
作者：
Chen, Kang;Yin, Lin;Huang, Xi
通讯作者：
Huang, Xi
DOI：
10.1083/jcb.200808080
发表时间：
2009-01-26
期刊：
The Journal of cell biology
影响因子：
--
作者：
N'Diaye EN;Branda CS;Branda SS;Nevarez L;Colonna M;Lowell C;Hamerman JA;Seaman WE
通讯作者：
Seaman WE
NLRP3/ASC介导的肺泡巨噬细胞焦亡增强体外循环所致急性肺损伤中HMGB1的分泌
影响因子：
5
作者：
Hou, Lei;Yang, Zhongwei;Wang, Xiangrui
通讯作者：
Wang, Xiangrui
影响因子：
29.4
作者：
Correale, Carmen;Genua, Marco;Danese, Silvio
通讯作者：
Danese, Silvio