Abstract:The aim of this research was to explore the effects of Salmonella enterica serovar Typhi (S. Typhi) on macrophage apoptosis and tumor necrosis factor-related apoptosis inducing ligand (TRAIL) signaling pathway. Total RNAs at early and late stages of S. Typhi infection were extracted from THP-1 cells for transcriptome sequencing (RNA-seq). Quantitative PCR (qPCR) was used to detect the transcriptional levels of apoptosis-related genes and verify the results of RNA-seq. Flow cytometry and western blot were used to determine the levels of THP-1 apoptosis and apoptosis-related proteins. After neutralizing TRAIL antibody was added to the medium, the changes in apoptosis were detected by flow cytometry and western blot in the early stage of S. Typhi infection. The results demonstrated that, the transcriptional levels of caspase-3, caspase-8 and caspase-9 in THP-1 cells were significantly up-regulated in the late stage of S. Typhi infection. In the early and late stages of S. Typhi infection, the transcriptional levels of Tnfsf10, Tnfrsf10b, Tnf and Fas were up-regulated. The rate of apoptosis was significantly increased. The activation of caspase-3, caspase-8 and caspase-9 and the expression of TRAIL and DR5 in S. Typhi infected cells were higher than that in uninfected cells. Compared with the control group, the activation of caspase-3 and the apoptosis rate were significantly reduced in TRAIL antibody treated group. It was concluded that S. Typhi induces macrophage apoptosis partly by activating TRAIL signaling pathway.