Neutrophils inhibit CD8 T cells immune response by arginase-1 signaling in patients with sepsis.

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 BIFNγCD8 T and TNFαIFNγCD8 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.