Salmonella enterica serovar Typhimurium inhibits the innate immune response and promotes apoptosis in a ribosomal/TRP53-dependent manner in swine neutrophils
Salmonella enterica serovar Typhimurium inhibits the innate immune response and promotes apoptosis in a ribosomal/TRP53-dependent manner in swine neutrophils
复制标题
肠沙门氏菌鼠伤寒血清型抑制猪中性粒细胞的先天免疫反应并以核糖体/TRP53依赖性方式促进细胞凋亡
DOI：
10.1186/s13567-020-00828-3
复制
发表时间：
2020-08-27
影响因子：
4.4
通讯作者：
Yao, Min
中科院分区：
文献类型：
--
作者：
Huang, Tinghua;Jiang, Caiyun;Yao, Min
中性粒细胞是抵抗鼠伤寒沙门氏菌侵袭、增殖和损伤的第一屏障。然而，控制这种阻力的机制尚未完全了解。本研究建立了沙门氏菌感染猪中性粒细胞的体外模型，并通过深度测序和流式细胞术对细胞转录组进行了分析。结果表明，核糖体基因转录受到抑制，其中两个基因RPL 39和RPL 9与TRP53的激活有关。此外，几个重要的先天免疫基因也受到抑制。通过siRNA敲低RPL 39和RPL 9引起TRP53的约四倍上调。RPL 39和RPL 9的敲低也导致IFNG和TNF的显著下调，表明先天免疫应答的抑制。RPL 39和RPL 9的沉默还导致FAS、RB 1、CASP 6和GADD 45 A的上调，这些基因在细胞周期停滞和凋亡中起作用。首先用RPL 39 siRNA、RPL 9 siRNA、TRP53激活剂或TRP53抑制剂处理中性粒细胞，然后用沙门氏菌感染。RPL 39和RPL 9的敲低，或用TRP53激活剂处理，可以增加Salmonellain中性粒细胞的细胞内增殖。我们推测，沙门氏菌的毒力可以归因于细胞周期阻滞的增强和先天免疫反应的抑制，这使得细菌能够成功地在细胞内增殖。
Neutrophils are the first barriers for resisting the invasion, proliferation, and damage caused bySalmonellaTyphimurium. However, the mechanisms that control this resistance are not completely understood. In this study, we established an in vitroSalmonellainfection model in porcine neutrophils, and analyzed the cellular transcriptome by deep sequencing and flow cytometry. The results showed that ribosomal gene transcription was inhibited, and two of these genes, RPL39 and RPL9, were related toTRP53activation. Furthermore, several important innate immunity genes were also inhibited. Knock-down of RPL39 and RPL9 by siRNA caused an approximate fourfold up-regulation of TRP53. Knock-down of RPL39 and RPL9 also resulted in a significant down-regulation of IFNG and TNF, indicating an inhibition of the innate immune response. Silencing of RPL39 and RPL9 also resulted in the up-regulation of FAS, RB1, CASP6, and GADD45A, which play roles in cell cycle arrest and apoptosis. Neutrophils were either first treated with RPL39 siRNA, RPL9 siRNA, TRP53 activator, or TRP53 inhibitor, and then infected withSalmonella. Knock-down of RPL39 and RPL9, or treatment with TRP53 activator, can increase the intracellular proliferation ofSalmonellain neutrophils. We speculate that much of theSalmonellavirulence can be attributed to the enhancement of cell cycle arrest and the inhibition of the innate immune response, which allows the bacteria to successfully proliferate intracellularly.