IL-15 complexes induce NK- and T-cell responses independent of type I IFN signaling during rhinovirus infection.
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-15Rα, which in turn were required for NK- and CD8(+) T-cell responses. Treatment with IL-15-IL-15Rα complexes (IL-15c) boosted RV-induced expression of IL-15, IL-15Rα, IFN-γ, CXCL9, and CXCL10 followed by recruitment of activated, IFN-γ-expressing NK, CD8(+), and CD4(+) T cells. Treating infected IFNAR1(-/-) mice with IL-15c similarly increased IL-15, IL-15Rα, IFN-γ, 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-γ and cellular immunity to RV was mediated by IL-15 and IL-15Rα. 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-γ expression and lymphocyte responses.
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, UK.
A
A
Jayaraman
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, UK [4] Imperial College Healthcare National Health Service Trust, London, UK.
D J
DJ
Jackson
Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, UK.
S D
SD
Message
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, UK.
R M
RM
Pearson
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, UK.
J
J
Aniscenko
Sezione 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, Italy.
G
G
Caramori
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, UK [4] Imperial College Healthcare National Health Service Trust, London, UK.
P
P
Mallia
Sezione 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, Italy.
A
A
Papi
Novartis Institute for Biomedical Research, Horsham, UK.
B
B
Shamji
Novartis Institute for Biomedical Research, Horsham, UK.
M
M
Edwards
Novartis Institute for Biomedical Research, Horsham, UK.
J
J
Westwick
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, UK [4] Imperial College Healthcare National Health Service Trust, London, UK.
T
T
Hansel
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, UK.
L A
LA
Stanciu
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, UK [4] Imperial College Healthcare National Health Service Trust, London, UK.
S L
SL
Johnston
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, UK.
N W
NW
Bartlett
D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D019409:Interleukin-15 / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D010850:Picornaviridae Infections / Q000276:immunology*; D012229:Rhinovirus / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D015854:Up-Regulation
D007370:Interferon Type I; D019409:Interleukin-15