IL-22 exacerbates weight loss in a murine model of chronic pulmonary Pseudomonas aeruginosa infection

J Cyst Fibros. 2016 Nov;15(6):759-768. doi: 10.1016/j.jcf.2016.06.008. Epub 2016 Jul 1.

Abstract

Background: Interleukin (IL)-22 is a critical mediator of mucosal immunity and tissue regeneration, protecting against a number of respiratory pathogens. Whether IL-22 confers protection against chronic Pseudomonas aeruginosa (PA) infection in cystic fibrosis (CF) is unknown.

Methods: Explanted CF lungs were examined for IL-22 production and immune-localization. A murine model of persistent pulmonary PA infection was used to examine production of IL-22 following infective challenge. The role of IL-22 was examined using IL-22 knockout (KO) animals.

Results: IL-22 is produced within the adult CF lung and localizes to the airway epithelium. IL-22 is produced by murine pulmonary lymph node cells following lung infection. The absence of IL-22 resulted in no significant difference in acute mortality, bacterial burden, chronic infection rates, histological changes or neutrophilic inflammation in the chronic PA infection model. However, IL-22 KO animals lost less weight following infection.

Conclusion: IL-22 is produced in the CF lung and in response to PA infection yet is dispensable in protection against chronic pulmonary P. aeruginosa infection in a murine model. However, we identified a novel role for the cytokine in promoting infection-related weight-loss, a significant prognostic factor in the CF population.

Keywords: Chronic infection; Cystic fibrosis; Interleukin-22; Mucosal immunity; Pseudomonas aeruginosa.

MeSH terms

  • Animals
  • Chronic Disease
  • Cystic Fibrosis* / immunology
  • Cystic Fibrosis* / microbiology
  • Disease Models, Animal
  • Interleukin-22
  • Interleukins* / analysis
  • Interleukins* / immunology
  • Lung / immunology*
  • Mice
  • Mucus / immunology
  • Pneumonia* / immunology
  • Pneumonia* / microbiology
  • Pneumonia* / physiopathology
  • Protective Factors
  • Pseudomonas Infections* / diagnosis
  • Pseudomonas Infections* / immunology
  • Pseudomonas Infections* / physiopathology
  • Pseudomonas aeruginosa / isolation & purification*

Substances

  • Interleukins