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IL-27 controls sepsis-induced impairment of lung antibacterial host defence
  1. Ju Cao1,
  2. Fang Xu2,
  3. Shihui Lin2,
  4. Zhixin Song3,
  5. Lipin Zhang1,
  6. Peng Luo1,
  7. Huajian Xu1,
  8. Dairong Li4,
  9. Ke Zheng5,
  10. Guosheng Ren5,
  11. Yibing Yin3
  1. 1Department of Laboratory Medicine, The Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China
  2. 2Department of Emergency and Intensive Care Unit, The Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China
  3. 3Key Laboratory of Diagnostic Medicine designated by the Ministry of Education, Chongqing Medical University, Chongqing, China
  4. 4Department of Respiratory Disease, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
  5. 5Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
  1. Correspondence to Dr Ju Cao, Department of Laboratory Medicine, The Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing 400016, China; caoju723{at}163.com

Abstract

Background Interleukin 27 (IL-27) is an important cytokine regulating host immune responses. However, its role in sepsis-induced immunosuppression remains unclear.

Aim 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.

  • Bacterial Infection
  • Pneumonia
  • Respiratory Infection

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