TY - JOUR T1 - Type I interferons and IL-15 regulate antiviral cellular responses to rhinovirus infection JF - European Respiratory Journal JO - Eur Respir J VL - 42 IS - Suppl 57 SP - 1494 AU - Annabelle Jayaraman AU - Sebastian Johnston AU - Nathan Bartlett Y1 - 2013/09/01 UR - http://erj.ersjournals.com/content/42/Suppl_57/1494.abstract N2 - Rhinoviruses (RV) are a global burden on respiratory health, particularly for those with chronic respiratory diseases such as asthma. The lack of treatments for RV-induced diseases inspires further studies into immune mechanisms of disease. IL-15 and NK cells are critical for defence against many viruses, but their role during RV infections has not been defined. Hypothesis IL-15, induced by type I interferons (IFNs), is critical for NK cell responses in the lungs during RV infection. Aims Use mouse models of RV infection with modulation of IL-15 and/or type I IFN signalling and assess airway inflammation. Results RV-1B infection induced upregulation of IL-15 gene and protein expression at day 1 in lung tissue (2.5-fold P<0.001) and was proceeded by an activated (increased CD69, GranzymeB and IFN-γ expression) NK cell response in the lungs at days 2-4; neutralisation of airway IL-15 with a monoclonal antibody impaired NK and CD8+ T cell responses. RV-induced IL-15, NK and CD8+ T cell responses were deficient (P<0.01) in type I IFN receptor knockout (IFNAR1-/-) mice; however, intranasal administration of IL-15c at the time of infection restored these responses in IFNAR1-/- mice and boosted them in wild type (WT) mice. IL-15c also significantly increased IFN-γ expression in WT and IFNAR1-/- mice and IFN stimulated genes PKR, OAS and IP-10 in WT mice during infection. This study demonstrates the necessity of type I IFN signalling for RV-induced IL-15, which is important for NK cell, CD8+ T cell and IFN-mediated antiviral responses. These data identify type I IFNs and IL-15 as potential therapeutics to prevent/treat RV-induced diseases such as asthma exacerbations. ER -