Exacerbation of experimental asthma depends on IL-15 and NK cells

Abstract

Background: Viral infections of the lung are the major cause of acute asthma exacerbations. Double-stranded RNA motifs, produced during the replication of respiratory viruses, can trigger immune responses via activation of Toll-like receptor 3 or RIG-I. We have previously shown that local application of the synthetic TLR-3/RIG-I activator poly (I:C) alone is sufficient to trigger exacerbation of experimental allergic asthma in mice, which is mainly driven by IL-17 and NK cells. Aim: This study aimed at identifying the regulatory mechanisms of IL-15 in experimental asthma exacerbation and identifying possible other involved lung immune cells. Methods: Therefore, poly (I:C) was applied intratracheally to mice with already established experimental allergic asthma to trigger acute exacerbation. Lung function, airway inflammation, cytokine expression, and mucus production was assessed in wild-type (WT) mice, mice without NK cells by antibody depletion (anti-asialo Ab), and mice deficient for IL-15 and IL-15Rα. FACS stainings for different leukocyte populations were performed. Results: Poly (I:C)-induced exacerbation of experimental asthma in WT mice is characterized by aggravation of airway inflammation, mucus production and airway hyperresponsiveness, which was associated with infiltration of eosinophils and changes in lung ILCs and CD11c+ cell populations. Such an exacerbation of experimental asthma could also be evoked in IL-23p19 deficient mice, but not in NK cell depleted mice or animals lacking IL-15 or IL15Rα. Conclusion: These results indicate a critical role for IL-15 and suggests changes in lung ILC and CD11c+ cell population as potential players in the immunopathology of experimental asthma exacerbations.