Brucella induces unfolded protein response and inflammatory response via GntR in alveolar macrophages.
Brucella induces unfolded protein response and inflammatory response via GntR in alveolar macrophages.
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布鲁氏菌通过肺泡巨噬细胞中的 GntR 诱导未折叠蛋白反应和炎症反应
DOI：
10.18632/oncotarget.23706
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发表时间：
2018-01-12
期刊：
影响因子：
--
通讯作者：
Wang AH
中科院分区：
文献类型：
--
作者：
Zhou D;Zhi FJ;Qi MZ;Bai FR;Zhang G;Li JM;Liu H;Chen HT;Lin PF;Tang KQ;Liu W;Jin YP;Wang AH
布鲁氏菌是一种在世界范围内引起人畜共患布鲁氏菌病的胞内细菌。肺泡巨噬细胞(AM)是吸入性布鲁氏菌的主要细胞靶点。布鲁氏菌通过毒力因子阻断免疫监视并激发内质网(ER)压力在巨噬细胞中复制。GntR调节因子家族是控制布鲁氏菌毒力和细胞内存活的重要毒力因子。然而，宿主-病原体相互作用的详细潜在机制却知之甚少。本研究构建了BSS2II0438突变体(ΔGntR)。在ΔGntR中，IV型分泌系统(T4SS)毒力因子基因(VirB2、VirB6和VirB8)表达下调。ΔGntR能在GAMs中感染并高滴度增殖，与亲本株相比无显著差异。在细胞周期的早期阶段，ΔGntR感染使内质网应激标记基因GRP78、ATF6和PERK的表达增加，而在细胞周期的晚期降低这些基因的表达。ΔGntR显著增加了处于非活动内质网应激状态的布鲁氏菌CFU的数量。同时，ΔGntR感染可使干扰素-γ、IL-1β和肿瘤坏死因子-α水平升高，提示ΔGntR可诱导炎性细胞因子IL-10的分泌，但不能诱导抗炎细胞因子IL-10的分泌。综上所述，我们的结果阐明了GntR在猪链霉菌中的作用。S2毒力表达，并阐明GntR可能参与了布鲁氏菌诱导的GAMs中UPR和炎症反应的信号通路。
Brucella is an intracellular bacterium that causes the zoonosis brucellosis worldwide. Alveolar macrophages (AM) constitute the main cell target of inhaled Brucella. Brucella thwarts immune surveillance and evokes endoplasmic reticulum (ER) stress to replicate in macrophages via virulence factors. The GntR regulators family was concentrated as an important virulence factor in controlling virulence and intracellular survival of Brucella. However, the detailed underlying mechanism for the host-pathogen interaction is poorly understood. In this study the BSS2_II0438 mutant (ΔGntR) was constructed. The type IV secretion system (T4SS) virulence factor genes (VirB2, VirB6, and VirB8) were down-expression in ΔGntR. ΔGntR could infect and proliferate to high titers in GAMs without a significant difference compared with the parental strain. ΔGntR infection increased the expression of ER stress marker genes GRP78, ATF6, and PERK in the early stages of its intracellular cycle but decreased the expression of these genes in the late stages. ΔGntR increased greatly the number of Brucella CFUs in the inactive ER stress state in GAMs. Meanwhile, ΔGntR infection increased the levels of IFN-γ, IL-1β, and TNF-α, indicating ΔGntR could induce the secretion of inflammatory but not anti-inflammatory cytokines IL-10. Taken together, our results clarified the role of the GntR in B. suis. S2 virulence expression and elucidated that GntR is potentially involved in the signaling pathway of the Brucella-induced UPR and inflammatory response in GAMs.
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影响因子：
30.3
作者：
Starr T;Child R;Wehrly TD;Hansen B;Hwang S;López-Otin C;Virgin HW;Celli J
通讯作者：
Celli J
影响因子：
5.7
作者：
Wang X;Lin P;Li Y;Xiang C;Yin Y;Chen Z;Du Y;Zhou D;Jin Y;Wang A
通讯作者：
Wang A
影响因子：
--
作者：
Wallach, JC;Samartino, LE;Baldi, PC
通讯作者：
Baldi, PC
影响因子：
3.1
作者：
Haine, V;Sinon, A;De Bolle, X
通讯作者：
De Bolle, X
影响因子：
5.5
作者：
Salez, L;Singer, M;Chignard, M
通讯作者：
Chignard, M