Salmonella enterica serovar Typhimurium inhibits the innate immune response and promotes apoptosis in a ribosomal/TRP53-
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RESEARCH ARTICLE
Salmonella enterica serovar Typhimurium inhibits the innate immune response and promotes apoptosis in a ribosomal/ TRP53‑dependent manner in swine neutrophils Tinghua Huang, Caiyun Jiang, Min Yang, Hong Xiao, Xiali Huang, Lingbo Wu and Min Yao*
Abstract Neutrophils are the first barriers for resisting the invasion, proliferation, and damage caused by Salmonella Typhimurium. However, the mechanisms that control this resistance are not completely understood. In this study, we established an in vitro Salmonella infection 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 to TRP53 activation. 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 with Salmonella. Knock-down of RPL39 and RPL9, or treatment with TRP53 activator, can increase the intracellular proliferation of Salmonella in neutrophils. We speculate that much of the Salmonella virulence 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. Keyword: porcine, neutrophils, deep-sequencing, Salmonella, RPL39, RPL9, TRP53 Introduction Salmonella enterica serovar Typhimurium is a Gramnegative facultative intracellular bacterium that colonizes both animals and humans [1]. Pigs carrying Salmonella can shed bacteria on a farm, which may subsequently lead to the bacterial contamination of pig carcasses in a slaughterhouse, thereby posing a serious threat to the swine industry [2]. A Salmonella infection is a dynamic process that involves the interaction between various immune cells and the bacteria. Burton et al. *Correspondence: [email protected] College of Animal Science, Yangtze University, 434025 Jingzhou, Hubei, China
demonstrated through single cell analysis and computer modeling that Salmonella bacteria can survive inside macrophages but are partially killed when engulfed by neutrophils and inflammatory monocytes [3]. The main mechanisms by which bacteria are effectively killed are through the production of a lethal concentration of reactive oxygen species (ROS) and hypochloric acid in phagocytes [4]. When Salmonella is engulfed by macrophages, the bacteria release a series of virulence factors through the type III secretion system, which modulates lysosome and vesicle maturation. This may reduce t
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