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.

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.

• Authors: Ju Cao, Fang Xu, Shihui Lin, Zhixin Song, Lipin Zhang, Peng Luo, Huajian Xu, Dairong Li, Ke Zheng, Guosheng Ren, Yibing Yin
• Journal: Thorax (Thorax) Vol. 69 Issue 10 Pg. 926-37 (Oct 2014) ISSN: 1468-3296 [Electronic] England
• PMID: 25074706 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Chemical References

• Interleukin-27

Topics

• Animals
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Immune Tolerance
• Interleukin-27 (physiology)
• Macrophages, Alveolar (immunology, metabolism)
• Mice
• Mice, Knockout
• Neutrophil Infiltration (immunology)
• Pneumonia, Bacterial (immunology, metabolism, pathology)
• Pseudomonas Infections (immunology, metabolism, pathology)
• Pseudomonas aeruginosa (immunology)
• Sepsis (immunology, metabolism)