title: IL-27 controls sepsis-induced impairment of lung antibacterial host defence.
abstract: BACKGROUND
  Interleukin 27 (IL-27) is an important cytokine regulating host immune responses. However, its role in sepsis-induced immunosuppression remains unclear.
  
  
  OBJECTIVE
  To investigate the role of IL-27 in modulating sepsis-induced immunosuppression using a murine model of caecal ligation and puncture (CLP)-induced sepsis followed by secondary challenge with Pseudomonas aeruginosa.
  
  
  METHODS
  CLP or sham surgery was performed in wild-type (WT) and IL-27 receptor (IL-27R)/WSX-1 knockout (KO) mice, and then mice were infected with intratracheal P aeruginosa.
  
  
  RESULTS
  IL-27 was upregulated in patients with sepsis and septic mice. Following sepsis and secondary intrapulmonary bacterial challenge, IL-27R KO mice had higher survival rates and improved bacterial clearance from lung and blood compared with WT mice, which was associated with early increased pulmonary cytokine/chemokine production, as well as enhanced neutrophil recruitment to airspaces. Neutralisation of IL-27 in septic mice significantly improved survival and clearance of bacteria from the lungs of septic mice infected with P aeruginosa, and direct application of recombinant IL-27 could increase susceptibility to P aeruginosa infection. The resistance of septic IL-27R KO mice to secondary P aeruginosa infection was abrogated by depletion of alveolar macrophages (AMs) and neutrophils. AMs from septic IL-27R KO mice had higher bacterial uptake and killing capacities, enhanced cytokine/chemokine production, and increased expression of costimulatory molecules compared with those from WT mice, while neutrophils from septic IL-27R KO mice had increased bacterial killing ability and higher expression of adhesion molecule Mac-1 compared with WT neutrophils.
  
  
  CONCLUSIONS
  IL-27 is an important mediator of sepsis-induced impairment of lung antibacterial host defence.
authors: Department of Laboratory Medicine, The Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China.
authors: Ju
authors: J
authors: Cao
authors: Department of Emergency and Intensive Care Unit, The Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China.
authors: Fang
authors: F
authors: Xu
authors: Department of Emergency and Intensive Care Unit, The Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China.
authors: Shihui
authors: S
authors: Lin
authors: Key Laboratory of Diagnostic Medicine designated by the Ministry of Education, Chongqing Medical University, Chongqing, China.
authors: Zhixin
authors: Z
authors: Song
authors: Department of Laboratory Medicine, The Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China.
authors: Lipin
authors: L
authors: Zhang
authors: Department of Laboratory Medicine, The Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China.
authors: Peng
authors: P
authors: Luo
authors: Department of Laboratory Medicine, The Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China.
authors: Huajian
authors: H
authors: Xu
authors: Department of Respiratory Disease, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors: Dairong
authors: D
authors: Li
authors: Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors: Ke
authors: K
authors: Zheng
authors: Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors: Guosheng
authors: G
authors: Ren
authors: Key Laboratory of Diagnostic Medicine designated by the Ministry of Education, Chongqing Medical University, Chongqing, China.
authors: Yibing
authors: Y
authors: Yin
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007108:Immune Tolerance; D064094:Interleukin-27 / Q000502:physiology*; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000276:immunology; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011552:Pseudomonas Infections / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D018805:Sepsis / Q000276:immunology* / Q000378:metabolism
chemical_list: D064094:Interleukin-27
keywords: Bacterial Infection; Pneumonia; Respiratory Infection