CD177+ neutrophils exacerbate septic lung injury via the NETs/AIM2 pathway: An experimental and bioinformatics study.

BACKGROUND

Acute lung injury (ALI) is one of the most common complications of sepsis. However, the underlying mechanisms and effective treatment strategies remain poorly understood. Immune cells are crucial in sepsis-induced lung injury, yet the heterogeneity of the immune cell populations involved in this context is not well characterized.

METHODS

This study established a Cecal Ligation and Puncture (CLP) mouse model and employed single-cell sequencing along with molecular biology experimental methods to identify the primary functional subgroups of immune cells associated with sepsis-induced ALI, thereby elucidating the key mechanisms related to sepsis-induced ALI.

RESULTS

Our analysis revealed that, in comparison to normal mice, the top 100 differentially expressed genes (DEGs) in septic lung tissue during the acute phase predominantly originate from neutrophils. Cd177 antigen (Cd177)+ neutrophils represent the predominant subpopulation of neutrophils in septic lung tissue. These cells exhibit unique pro-inflammatory and oxidative stress characteristics, and they are capable of producing excessive neutrophil extracellular traps (NETs). NETs can aggravate ALI by activating Absent in Melanoma 2 (AIM2) inflammasome. Furthermore, we discovered that melatonin could effectively inhibit the infiltration of Cd177+ neutrophils in septic lung tissue, reduce the expression levels of NETs, and diminish the activation of AIM2, thereby improving lung injury.

CONCLUSION

Our research provides novel insights and potential therapeutic targets for the treatment of sepsis-induced ALI.