Polymorphonuclear cells show features of dysfunctional activation during fatal sepsis

Sepsis and septic shock remain leading causes of morbidity and mortality for patients in Intensive care unit. In their early phase, immune cells produce various cytokines which lead to the prompt activation of the immune system. Polymorphonuclear leukocytes (PMNs) respond to different signals producing inflammatory factors and executing their antibacterial mechanisms, resulting in the engulfment and elimination of invading pathogens. However, long-term activation caused by various inflammatory signals produced during sepsis progression, can lead to the alteration of PMN signaling and subsequent defects in their functionality. Here we analyzed the PMNs samples from 34 patients in septic shock, we focused on PMNs gene expression and proteome changes caused by septic shock. We reveal that, compared to those of patients who survived, PMNs from patients who had a fulminant outcome were characterized by a dysfunctional hyper-activation, showing an altered metabolism, higher longevity and recent exit from cell cycle. We believe that this multi-omics approach, although limited, served to pinpoint the alterations in PMNs’ functionality, which may be reverted by targeted treatments. RNAseq of human polymorphonuclear cells isolated from the peripheral blood of patients affected by septic shock