Abstract
BackgroundInterleukin (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. MethodsExplanted 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. ResultsIL-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. ConclusionIL-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.
Highlights
Pseudomonas aeruginosa (PA) remains an important pathogen in cystic fibrosis (CF) with its extensive armament of virulence factors and evolving resistance profile [1,2]
IL-22 was identified, via immunohistochemistry of explanted CF lung tissue, to localize to the airway epithelium with more sparse staining in lung parenchyma (Fig. 1b)
We found no difference in IL-22, and other related cytokines, in the lungs of animals treated with PA compared with sterile bead-treated animals
Summary
Pseudomonas aeruginosa (PA) remains an important pathogen in cystic fibrosis (CF) with its extensive armament of virulence factors and evolving resistance profile [1,2]. Whether IL-22 confers protection against chronic Pseudomonas aeruginosa (PA) infection in cystic fibrosis (CF) is unknown. A murine model of persistent pulmonary PA infection was used to examine production of IL-22 following infective challenge. IL-22 is produced by murine pulmonary lymph node cells following lung 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.
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