Regulation of host cell pyroptosis and cytokines production by Mycobacterium tuberculosis effector PPE60 requires LUBAC mediated NF-κB signaling
Regulation of host cell pyroptosis and cytokines production by Mycobacterium tuberculosis effector PPE60 requires LUBAC mediated NF-κB signaling
复制标题
结核分枝杆菌效应子 PPE60 对宿主细胞焦亡和细胞因子产生的调节需要 LUBAC 介导的 NF-κ B 信号传导
DOI：
10.1016/j.cellimm.2018.10.009
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发表时间：
2019-01-01
影响因子：
4.3
通讯作者：
Xie, Jianping
中科院分区：
文献类型：
--
作者：
Cong, Zhen;Kuang, Zhongmei;Xie, Jianping
由结核分枝杆菌感染引起的结核病仍然是全球公共卫生威胁。结核分枝杆菌的成功很大程度上归功于它对宿主细胞命运的操纵。深入探讨了结核分枝杆菌PE/PPE家族效应物在宿主命运中的作用。本研究利用重组Rv3478对PPE60 （Rv3478）的作用进行了表征。PPE60可以通过caspases/NLRP3/gasdermin促进宿主细胞焦亡。促炎细胞因子如IL-1 β、IL-6、IL-12p40和tnf - α的产生被PPE60改变。我们发现LUBAC通过使用线性泛素链组装复合物（LUBAC）特异性抑制剂胶质毒素参与了ppe60诱导的NF-kappa B信号传导。PPE60重组耻垢分枝杆菌在巨噬细胞内的存活率增加，并且对低pH、表面胁迫和抗生素暴露等应激的抵抗力增强。首次报道结核分枝杆菌效应物PPE60可通过lubac介导的NF-kappa B信号通路调节宿主细胞命运。
Tuberculosis, caused by Mycobacterium tuberculosis infection, remains a global public health threat. The success of M. tuberculosis largely contributes to its manipulation of host cell fate. The role of M. tuberculosis PE/PPE family effectors in the host destiny was intensively explored. In this study, the role of PPE60 (Rv3478) was characterized by using Rv3478 recombinant M. smegmatis. PPE60 can promote host cell pyroptosis via caspases/NLRP3/gasdermin. The production of pro-inflammatory cytokines, such as IL-1 beta, IL-6, IL-12p40 and TNF-alpha was altered by PPE60. We found that LUBAC was involved in PPE60-elicited NF-kappa B signaling by using Linear Ubiquitin Chain Assembly Complex (LUBAC)-specific inhibitor gliotoxin. The PPE60 recombinant M. smegmatis survival rate within macrophages is increased, as well as elevated resistance to stresses such as low pH, surface stresses and antibiotics exposure. For a first time it is firstly reported that M. tuberculosis effector PPE60 can modulate the host cell fate via LUBAC-mediated NF-kappa B signaling.