Role of IL-22 in the protection against nontypeable Haemophilus influenza infection - 04/04/15

Haemophilus influenzae infections are a major cause of disease exacerbation in inflammatory disorders including chronic obstructive pulmonary disease (COPD). During infection, IL-17 and IL-22 are essential for the control of both neutrophil inflammation and anti-microbial response. We observed a deficient IL-22 response during H. influenzae-induced exacerbations in COPD mice. Since the role of IL-22 is unknown, we investigate the function of this cytokine in the protection against nontypeable H. influenza (NTHI) in mice.

IL-22-deficient (IL-22^-/−) and wild-type mice (C57BL/6) were exposed or not to sublethal dose of NTHI by intranasal route. The pro-Th1 (IL-2, IFN-γ and TNFα) and pro-Th17 (IL-1β, IL-6, IL-17 and IL-22) cytokines levels were measured by ELISA in blood, bronchoalveolar lavage (BAL) and lung tissues, 24h and 48h post-infection. Cytokine production was also evaluated in supernatants of spleen and lung cells after restimulation with specific Ag. Cellular profile, lung inflammation and tissue remodeling were evaluated by flow-cytometry and histological analysis, respectively.

In WT mice, infection with NTHI strongly increased the levels of IL-17 and IL-22 in the lungs. Infected IL-22^-/-mice revealed a higher bacterial load in the lung associated with an increased inflammatory reaction as shown by the levels of TNFα, IL6 in the BAL and IFNγ in the lung. In contrast, naïve mice cleared the bacteria within 48h. This defect in bacterial clearance is related with a lower production of IL-17 in the BAL and in Ag-stimulated lung cells. Histopathological and cytometric analysis confirmed that cellular infiltration with neutrophils and NK cells in the alveolar spaces and lung tissue was increased in IL-22^-/-mice. IL-22^-/-mice expressed a severe acute pneumonia with congestion of alveolar space at 48h post-infection whereas WT mouse showed an acute alveolitis of moderate intensity.

These data show that a deficient production of IL-22 triggers a susceptibility to infections by H. influenzae and a more deleterious lung inflammatory reaction. Treatments favoring a Th17 response would be a potential therapeutic strategy in lung inflammatory disorders with exacerbation episodes.