ID: 111

The pathophysiological mechanisms driving exaggerated inflammation and tissue damage, associated to un-resolved airway infections, in the context of chronic lung diseases remain to be elucidated. In the host-pathogen interplay, two-component defense responses, resistance and tolerance, are increasingly described. Recent reports prompt the hypothesis that chronic lung disease associated to persistent infections, such as Pseudomonas aeruginosa , may be mediated by IL-17 immunity. Thus, we dissected the IL17 pathway during long term chronic infection by P. aerginosa in murine models. When C57Bl/6 mice were infected with P. aeruginosa embedded in agar beads for one month, we found that IL-17A is sustained and secreted by CD4+ T cells at the advanced phases. To directly address the role of IL-17, we infected IL-17a − / −, IL-17ra − / − and congenic controls comparing their host response. Deficiency of IL-17A/IL-17RA axis was associated with: (i) increased incidence of chronic infection and bacterial burden indicating its role in the host resistance to P. aeruginosa ; (ii) reduced markers of tissue damage (pro-MMP-9, elastin degradation, TGF- β 1), cytokines levels (KC, IL-33) and tissue innate infiltrating cells, proving alteration of host tolerance, through tissue damage control. Blockade of IL-17 activity, by an anti-IL-17A mAb starting from ten days post-infection did not affect host resistance in terms of bacterial load and incidence of infection, but increase mainly host tolerance, reducing exaggerated neutrophils infiltration, and levels of KC, pro-MMP-9, TGF- β 1. Overall, the IL-17A cytokine represents a potential host-based intervention to ameliorate lung physiology without compromising host resistance against pathogens during chronic airway infection.