Abstract
BACKGROUND: Patients with sepsis often exhibit an acute inflammatory response, followed by an immunosuppressive phase with a poor immune response. However, the underlying mechanisms have not been fully elucidated. METHODS: We sought to comprehensively characterize the transcriptional changes in neutrophils of patients with sepsis by transcriptome sequencing. Additionally, we conducted a series of experiments, including real-time quantitative polymerase chain reaction (RT-qPCR) and flow cytometry to investigate the role of arginase-1 signaling in sepsis. RESULTS: Through the analysis of gene expression profiles, we identified that the negative regulation of T cell activation signaling was enriched, and the expression of arginase-1 was high in neutrophils from patients with sepsis. Furthermore, we conducted flow cytometry and found that the function of CD8(+) T cells in septic patients was impaired. Moreover, neutrophils from septic patients inhibited the percentage of polyfunctional effector CD8(+) T cells through arginase-1. Additionally, the proportions of granzyme B(+)IFN(-)γ(+)CD8(+) T and TNF(-)α(+)IFN(-)γ(+)CD8(+) T cells increased after inhibition of arginase-1 signaling. CONCLUSION: The impaired effector function of CD8(+) T cells could be restored by blocking arginase-1 signaling in patients with sepsis.