title: Up-regulation of programmed cell death 1 ligand 1 on neutrophils may be involved in sepsis-induced immunosuppression: an animal study and a prospective case-control study.
abstract: BACKGROUND
  Recent studies have shown that neutrophils may display an antigen-presenting function and inhibit lymphocyte proliferation by expressing programmed cell death 1 ligand 1 (PD-L1). The current study was performed to investigate the effect of neutrophils and their pathophysiological significance during sepsis.
  
  
  METHODS
  Neutrophil PD-L1 expression was determined in both septic mice (n = 6) and patients (n = 41). Neutrophils from septic mice were subtyped into PD-L1 and PD-L1 populations to determine their phenotypes and functions. Septic neutrophils were cocultured with lymphocytes to observe the effect of septic neutrophils on lymphocyte apoptosis.
  
  
  RESULTS
  The PD-L1 level on neutrophils from septic mice was significantly up-regulated (21.41 ± 4.76%). This level increased with the progression of sepsis and the migration of neutrophils from the bone marrow to the blood and peritoneal cavity. The percentages of CD11a, CD62L, and C-C chemokine receptor type 2 were lower, whereas the percentages of CD16 and CD64 were higher on PD-L1 neutrophils than on PD-L1 neutrophils. The migratory capacity of PD-L1 neutrophils was compromised. Septic neutrophils induced lymphocyte apoptosis via a contact mechanism, and this process could be reversed by anti-PD-L1 antibody. PD-L1 was also up-regulated on neutrophils from patients with severe sepsis (14.6% [3.75%, 42.1%]). The levels were negatively correlated with the monocyte human leukocyte antigen-DR level and positively correlated with the severity of septic patients. Neutrophil PD-L1 was a predictor for the prognosis of severe sepsis, with an area of 0.74 under the receiver operating curve.
  
  
  CONCLUSIONS
  PD-L1 is up-regulated on neutrophils during sepsis, which may be related to sepsis-induced immunosuppression.
authors.affiliation: From the Department of Anesthesiology and Intensive Care Medicine, Changhai Hospital, the Second Military Medical University, Shanghai, China (J.-F.W., J.-B.L., W.-J.Y., J.-J.B., X.-J.W., K.-M.Z., X.-M.D.); and Department of Anesthesiology and Intensive Care, Shanghai Ninth People's Hospital, Shanghai Jiaotong University, Shanghai, China (Y.-J.Z.).
authors.forename: Jia-Feng
authors.initials: JF
authors.lastname: Wang
authors.forename: Jin-Bao
authors.initials: JB
authors.lastname: Li
authors.forename: Yan-Jun
authors.initials: YJ
authors.lastname: Zhao
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Yi
authors.forename: Jin-Jun
authors.initials: JJ
authors.lastname: Bian
authors.forename: Xiao-Jian
authors.initials: XJ
authors.lastname: Wan
authors.forename: Ke-Ming
authors.initials: KM
authors.lastname: Zhu
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Deng
mesh_terms: D000368:Aged; D000818:Animals; D060890:B7-H1 Antigen / Q000096:biosynthesis*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism*; D011446:Prospective Studies; D018805:Sepsis / Q000276:immunology* / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human