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

Jayaraman, A, Jackson, DJ, Message, SD, Pearson, RM, Aniscenko, J, Caramori, G, Mallia, P, Papi, A, Shamji, B, Edwards, M, Westwick, J, Hansel, T, Stanciu, LA, 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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