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IL-15 complexes induce NK- and T-cell responses independent of type I IFN signaling during rhinovirus infection

Jayaraman, A and Jackson, DJ and Message, SD and Pearson, RM and Aniscenko, J and Caramori, G and Mallia, P and Papi, A and Shamji, B and Edwards, M and Westwick, J and Hansel, T and Stanciu, LA and Johnston, SL and Bartlett, NW (2014) IL-15 complexes induce NK- and T-cell responses independent of type I IFN signaling during rhinovirus infection. Mucosal Immunology.

Abstract

Rhinoviruses are among the most common viruses to infect man, causing a range of serious respiratory diseases including exacerbations of asthma and COPD. Type I IFN and IL-15 are thought to be required for antiviral immunity; however, their function during rhinovirus infection in vivo is undefined. In RV-infected human volunteers, IL-15 protein expression in fluid from the nasal mucosa and in bronchial biopsies was increased. In mice, RV induced type I IFN-dependent expressions of IL-15 and IL-15Ralpha, which in turn were required for NK- and CD8+ T-cell responses. Treatment with IL-15-IL-15Ralpha complexes (IL-15c) boosted RV-induced expression of IL-15, IL-15Ralpha, IFN-gamma, CXCL9, and CXCL10 followed by recruitment of activated, IFN-gamma-expressing NK, CD8+, and CD4+ T cells. Treating infected IFNAR1-/- mice with IL-15c similarly increased IL-15, IL-15Ralpha, IFN-gamma, and CXCL9 (but not CXCL10) expression also followed by NK-, CD8+-, and CD4+-T-cell recruitment and activation. We have demonstrated that type I IFN-induced IFN-gamma and cellular immunity to RV was mediated by IL-15 and IL-15Ralpha. Importantly, we also show that IL-15 could be induced via a type I IFN-independent mechanism by IL-15 complex treatment, which in turn was sufficient to drive IFN-gamma expression and lymphocyte responses.Mucosal Immunology advance online publication, 29 January 2014; doi:10.1038/mi.2014.2

Item Type: Article
Additional Information: NIBR author: Edwards, E institute: NIBR contributor address: 1] Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, UK [2] MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK [3] Centre for Respiratory Infections, Imperial College London, London, UK1] Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, UK [2] MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK [3] Centre for Respiratory Infections, Imperial College London, London, UK [4] Imperial College Healthcare National Health Service Trust, London, UKAirway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, UK1] Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, UK [2] MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK [3] Centre for Respiratory Infections, Imperial College London, London, UK1] Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, UK [2] MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK [3] Centre for Respiratory Infections, Imperial College London, London, UKSezione di Malattie dell'Apparato Respiratorio, Centro per lo Studio delle Malattie Infiammatorie Croniche delle Vie Aeree e Patologie Fumo Correlate dell'Apparato Respiratorio (CEMICEF), University of Ferrara, Ferrara, Italy1] Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, UK [2] MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK [3] Centre for Respiratory Infections, Imperial College London, London, UK [4] Imperial College Healthcare National Health Service Trust, London, UKSezione di Malattie dell'Apparato Respiratorio, Centro per lo Studio delle Malattie Infiammatorie Croniche delle Vie Aeree e Patologie Fumo Correlate dell'Apparato Respiratorio (CEMICEF), University of Ferrara, Ferrara, ItalyNovartis Institute for Biomedical Research, Horsham, UKNovartis Institute for Biomedical Research, Horsham, UKNovartis Institute for Biomedical Research, Horsham, UK1] Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, UK [2] MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK [3] Centre for Respiratory Infections, Imperial College London, London, UK [4] Imperial College Healthcare National Health Service Trust, London, UK1] Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, UK [2] MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK [3] Centre for Respiratory Infections, Imperial College London, London, UK1] Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, UK [2] MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK [3] Centre for Respiratory Infections, Imperial College London, London, UK [4] Imperial College Healthcare National Health Service Trust, London, UK1] Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, UK [2] MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK [3] Centre for Respiratory Infections, Imperial College London, London, UK
Date Deposited: 13 Oct 2015 13:12
Last Modified: 13 Oct 2015 13:12
URI: https://oak.novartis.com/id/eprint/22638

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