Salmonella Enterica Serovar Typhimurium Inhibits the Innate Immune Response and Promotes Apoptosis in a Ribosomal/TRP53-dependent Manner in Swine Neutrophils

Overview

Journal Vet Res

Publisher Biomed Central

Specialty Veterinary Medicine

Date 2020 Aug 29

PMID 32854785

Citations 10

Authors

Tinghua Huang

Caiyun Jiang

Min Yang

Hong Xiao

Xiali Huang

LingBo Wu

Min Yao

Affiliations

Soon will be listed here.

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.

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