HUWE1 mediates inflammasome activation and promotes host defense against bacterial infection

	HUWE1 mediates inflammasome activation and promotes host defense against bacterial infection
	Guo, Y; Li, LJ; Xu, T; Guo, XM; Wang, CM; Li, YH; Yang, YA; Yang, D; Sun, B; Zhao, XD; Shao, GZ; Qi, XP
	2020
发表期刊	JOURNAL OF CLINICAL INVESTIGATION
ISSN	0021-9738
卷号	130 期号:12 页码:6301-6316
摘要	The mechanism by which inflammasome activation is modulated remains unclear. In this study, we identified an AIM2-interacting protein, the E3 ubiquitin ligase HUWE1, which was also found to interact with NLRP3 and NLRC4 through the HIN domain of AIM2 and the NACHT domains of NLRP3 and NLRC4. The BH3 domain of HUWE1 was important for its interaction with NLRP3, AIM2, and NLRC4. Caspase-1 maturation, IL-1 beta release, and pyroptosis were reduced in Huwel-deficient bone marrow-derived macrophages (BMDMs) compared with WT BMDMs in response to stimuli to induce NLRP3, NLRC4, and AIM2 inflammasome activation. Furthermore, the activation of NLRP3, NLRC4, and AIM2 inflammasomes in both mouse and human cells was remarkably reduced by treatment with the HUWE1 inhibitor 818622. HUWE1 mediated the K27-linked polyubiquitination of AIM2, NLRP3, and NLRC4, which led to inflammasome assembly, ASC speck formation, and sustained caspase-1 activation. Huwel-deficient mice had an increased bacterial burden and decreased caspase-1 activation and IL-1 beta production upon Salmonella, Franciselia, or Acinetobacter baumannii infection. Our study provides insights into the mechanisms of inflammasome activation as well as a potential therapeutic target against bacterial infection.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/13594
专题	科研部门_病原菌感染与宿主免疫机制（齐晓朋）
推荐引用方式 GB/T 7714	Guo, Y,Li, LJ,Xu, T,et al. HUWE1 mediates inflammasome activation and promotes host defense against bacterial infection[J]. JOURNAL OF CLINICAL INVESTIGATION,2020,130(12):6301-6316.
APA	Guo, Y.,Li, LJ.,Xu, T.,Guo, XM.,Wang, CM.,...&Qi, XP.(2020).HUWE1 mediates inflammasome activation and promotes host defense against bacterial infection.JOURNAL OF CLINICAL INVESTIGATION,130(12),6301-6316.
MLA	Guo, Y,et al."HUWE1 mediates inflammasome activation and promotes host defense against bacterial infection".JOURNAL OF CLINICAL INVESTIGATION 130.12(2020):6301-6316.

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