Chronic obstructive pulmonary disease is a major health problem becoming a leading cause of morbidity and mortality worldwide. A large part of these disorders is associated with acute exacerbations resulting from
infection by bacteria, such as non-typeable Haemophilus influenzae (NTHi). Our understanding of the pathogenesis of these exacerbations is still elusive. We demonstrate herein that NTHi
infection of mice chronically exposed to cigarette
smoke (CS), an experimental model of
chronic obstructive pulmonary disease (
COPD), not only causes acute
pulmonary inflammation but also impairs the production of
interleukin (IL)-22, a
cytokine with potential anti-bacterial activities. We also report that mice lacking
IL-22, as well as mice exposed to CS, have a delayed clearance of NTHi bacteria and display enhanced alveolar wall thickening and
airway remodeling compared with controls. Supplementation with
IL-22 not only boosted bacterial clearance and the production of anti-microbial
peptides but also limited lung damages induced by
infection both in IL-22-/- and CS-exposed mice. In vitro exposure to CS extract altered the NTHi-induced
IL-22 production by spleen cells. This study shows for the first time that a defect in
IL-22 is involved in the acute exacerbation induced by NTHi
infection during experimental
COPD and opens the way to innovative therapeutic strategies.