当前位置: X-MOL 学术J. Immunol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Brucella Infection Regulates Thioredoxin-Interacting Protein Expression to Facilitate Intracellular Survival by Reducing the Production of Nitric Oxide and Reactive Oxygen Species
The Journal of Immunology ( IF 4.4 ) Pub Date : 2019-12-18 , DOI: 10.4049/jimmunol.1801550
Hai Hu 1 , Mingxing Tian 1 , Peng Li 1 , Xiang Guan 1 , Zhengmin Lian 1 , Yi Yin 1 , Wentao Shi 1 , Chan Ding 1, 2 , Shengqing Yu 2, 3
Affiliation  

Key Points Brucella decreased TXNIP to promote its intracellular growth in macrophages. Reduced TXNIP promotes Brucella intracellular growth via reduction of NO and ROS. The expression of iNOS and the production of NO were dependent on the Brucella T4SS. Thioredoxin-interacting protein (TXNIP) is a multifunctional protein that functions in tumor suppression, oxidative stress, and inflammatory responses. However, how TXNIP functions during microbial infections is rarely reported. In this study, we demonstrate that Brucella infection decreased TXNIP expression to promote its intracellular growth in macrophages by decreasing the production of NO and reactive oxygen species (ROS). Following Brucella abortus infection, TXNIP knockout RAW264.7 cells produced significantly lower levels of NO and ROS, compared with wild-type RAW264.7 cells. Inducible NO synthase (iNOS) inhibitor treatment reduced NO levels, which resulted in a dose-dependent restoration of TXNIP expression, demonstrating that the expression of TXNIP is regulated by NO. In addition, the expression of iNOS and the production of NO were dependent on the type IV secretion system of Brucella. Moreover, Brucella infection reduced TXNIP expression in bone marrow–derived macrophages and mouse lung and spleen. Knocked down of the TXNIP expression in bone marrow–derived macrophages increased intracellular survival of Brucella. These findings revealed the following: 1) TXNIP is a novel molecule to promote Brucella intracellular survival by reducing the production of NO and ROS; 2) a negative feedback–regulation system of NO confers protection against iNOS-mediated antibacterial effects. The elucidation of this mechanism may reveal a novel host surveillance pathway for bacterial intracellular survival.

中文翻译:

布鲁氏菌感染通过减少一氧化氮和活性氧的产生来调节硫氧还蛋白相互作用蛋白的表达以促进细胞内存活

关键点布鲁氏菌降低 TXNIP 以促进其在巨噬细胞中的细胞内生长。减少的 TXNIP 通过减少 NO 和 ROS 促进布鲁氏菌细胞内生长。iNOS 的表达和 NO 的产生依赖于布鲁氏菌 T4SS。硫氧还蛋白相互作用蛋白 (TXNIP) 是一种多功能蛋白,在肿瘤抑制、氧化应激和炎症反应中起作用。然而,很少报道TXNIP在微生物感染期间如何发挥作用。在这项研究中,我们证明布鲁氏菌感染降低了 TXNIP 表达,通过减少 NO 和活性氧 (ROS) 的产生来促进其在巨噬细胞中的细胞内生长。流产布鲁氏菌感染后,与野生型 RAW264.7 细胞相比,TXNIP 敲除 RAW264.7 细胞产生的 NO 和 ROS 水平显着降低。诱导型 NO 合酶 (iNOS) 抑制剂治疗降低了 NO 水平,导致 TXNIP 表达的剂量依赖性恢复,表明 TXNIP 的表达受 NO 调节。此外,iNOS的表达和NO的产生依赖于布鲁氏菌的IV型分泌系统。此外,布鲁氏菌感染降低了骨髓来源的巨噬细胞和小鼠肺脾中 TXNIP 的表达。骨髓源性巨噬细胞中 TXNIP 表达的敲低增加了布鲁氏菌的细胞内存活率。这些发现揭示了以下几点: 1) TXNIP 是一种通过减少 NO 和 ROS 的产生促进布鲁氏菌细胞内存活的新型分子;2) NO 的负反馈调节系统赋予对 iNOS 介导的抗菌作用的保护。
更新日期:2019-12-18
down
wechat
bug