IL-22 plays a key-role in nontypeable Haemophilus influenzae clearance in Chronic Obstructive Pulmonary Disease

Infection by Nontypeable Haemophilus influenzae (NTHi) often exacerbates chronic obstructive pulmonary disease (COPD). Th17 cytokines are essential in the anti-bacterial defense, however their role remains unknown in the protection against NTHi. Mice were chronically exposed to cigarette smoke to induce COPD symptoms or to ambient air (Air mice) and then challenged with NTHi. Infection with NTHi strongly increased the levels of IL-17 and IL-22 in the lungs of Air mice. Whereas IL-17 was increased in COPD mice after NTHi, IL-22 production was not increased due to a defective innate lymphocyte activation. To determine the implication of IL-22, IL-22^-/- mice were infected with NTHi. IL-22^-/- mice had higher bacterial load in the lung compared with WT mice. This was associated to an increased inflammatory reaction (TNF-α, IL-6 in the BAL and IFN-γ in the lung) and the recruitment of neutrophils and NK cells. A severe acute pneumonia with congestion of alveolar spaces was only observed in infected IL-22^-/- and COPD mice. Moreover, supplementation with recombinant IL-22 before NTHi challenge of COPD mice improved bacterial clearance and decreased inflammation. In conclusion, the defect in IL-22 related to COPD could explain the susceptibility to NTHi infection and the associated deleterious inflammation.