P75NTR+CD64+ neutrophils promote sepsis-induced acute lung injury

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2024-06, Vol.263, p.110206, Article 110206
• Main Authors: Fu, Di, Gao, Shan, Li, Jia-Nan, Cui, Yan-Hui, Luo, Yan-Wei, Zhong, Yan-Jun, Li, Qiao, Luo, Cong, Dai, Ru-Ping, Luo, Ru-Yi, Hu, Zhao-Lan
• Format: Article
• Language: English
• Subjects: CD64+ neutrophils; p75NTR; Phagocytosis; Sepsis-induced acute lung injury
• ISSN: 1521-6616; 1521-7035; 1521-7035
• DOI: 10.1016/j.clim.2024.110206

Patients suffering from sepsis-induced acute lung injury (ALI) exhibit a high mortality rate, and their prognosis is closely associated with infiltration of neutrophils into the lungs. In this study, we found a significant elevation of CD64+ neutrophils, which highly expressed p75 neurotrophin receptor (p75NTR) in peripheral blood of mice and patients with sepsis-induced ALI. p75NTR+CD64+ neutrophils were also abundantly expressed in the lung of ALI mice induced by lipopolysaccharide. Conditional knock-out of the myeloid lineage's p75NTR gene improved the survival rates, attenuated lung tissue inflammation, reduced neutrophil infiltration and enhanced the phagocytic functions of CD64+ neutrophils. In vitro, p75NTR+CD64+ neutrophils exhibited an upregulation and compromised phagocytic activity in blood samples of ALI patients. Blocking p75NTR activity by soluble p75NTR extracellular domain peptide (p75ECD-Fc) boosted CD64+ neutrophils phagocytic activity and reduced inflammatory cytokine production via regulation of the NF-κB activity. The findings strongly indicate that p75NTR+CD64+ neutrophils are a novel pathogenic neutrophil subpopulation promoting sepsis-induced ALI. [Display omitted] •p75NTR+CD64+ neutrophils are upregulated in mice or patients with sepsis-induced ALI.•Genetic deletion or blockade of p75NTR upregulated the phagocytic activity of CD64+ neutrophils in ALI mice.•p75NTR+CD64+ neutrophils are a novel subpopulation of pathogenic neutrophils that promote the sepsis associated with ALI.