Rhinovirus 16–induced IFN-⍺ and IFN-β are deficient in bronchoalveolar lavage cells in asthmatic patients - 31/05/12
, Michael R. Edwards, PhD a, b, c, Jonathan Macintyre, MD, BSc a, b, c, d, Ajerico del Rosario, BSc a, b, c, d, Eteri Bakhsoliani, MSc a, b, c, Maria-Belen Trujillo-Torralbo, BSc a, b, c, d, Onn Min Kon, MD, PhD d, Patrick Mallia, MD, PhD a, b, c, Mark McHale, PhD e, Sebastian L. Johnston, MD, PhD a, b, c, d
Corresponding author: Annemarie Sykes, MD, PhD, National Heart & Lung Institute, St Mary’s Campus, Imperial College London, W2 1PG, London, United Kingdom.Abstract |
Background |
Asthmatic patients have defective rhinovirus-induced IFN-β and IFN-λ production from bronchial epithelial cells and IFN-λ from bronchoalveolar lavage (BAL) cells. Whether bronchoalveolar lavage cells have defective type I interferon responses to rhinovirus is unknown, as are mechanisms explaining defective rhinovirus interferon induction in asthmatic patients.
Objective |
We sought to investigate rhinovirus induction of type I interferons in BAL and blood mononuclear cells from asthmatic patients and healthy subjects and to investigate mechanisms of any deficiency observed.
Methods |
BAL and blood mononuclear cells from atopic asthmatic patients and healthy subjects were infected with rhinovirus ex vivo. Interferon proteins were analyzed by using ELISA. mRNA expression of key components of interferon induction pathways were analyzed by using quantitative PCR.
Results |
Rhinovirus induction of type I interferon protein was delayed and deficient in BAL cells from asthmatic patients, and lower interferon levels were associated with greater airway hyperresponsiveness and skin prick test response positivity. Expression of Toll-like receptor (TLR) 3, TLR7, TLR8, retinoic acid–inducible gene I (RIG-I), melanoma differentiation–associated gene 5 (MDA-5), TIR domain–containing adapter-inducing IFN-β (TRIF), myeloid differentiation primary response gene 88 (MyD88), caspase recruitment domain adaptor inducing IFN-β (CARDIF), IL-1 receptor–associated kinase 4 (IRAK4), IκB kinase β (IKKB), IκB kinase ι (IKKI), interferon regulatory factors 3 and 7, and rhinovirus induction of expression of the virus-inducible molecules TLR3, TLR7, RIG-I, and MDA-5 were not impaired in these interferon-deficient BAL cells in asthmatic patients. Defective rhinovirus interferon induction was not observed in blood mononuclear cells.
Conclusions |
Rhinovirus induction of type I interferons in BAL cells is delayed and deficient and might be a marker of more severe asthma. Defective rhinovirus interferon induction in asthmatic patients was not accompanied by differences in the expression or induction of key molecules implicated in viral induction of interferons.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, interferon, rhinovirus, bronchoalveolar lavage cells, peripheral blood mononuclear cells, airway hyperresponsiveness
Abbreviations used : BAL, CARD, CARDIF, dsRNA, HBEC, IKKB, IKKI, IRAK4, IRF, MDA-5, MyD88, PRR, RIG-I, RV14, RV16, TLR, TRIF
Plan
| Supported by grants from the Medical Research Council (MRC project grant G0601236 and Centre grant 100758 and an MRC Clinical Research Fellowship [to A.S.]), the British Lung Foundation (grant P06/3), the Wellcome Trust (grant 083567/Z/07/Z for the Centre for Respiratory Infection), Asthma UK (grants 05/067 and 08/048 and Asthma UK Fellowship RF07/04 [to M.R.E.], ERC FP7 Advanced grant 233015 [to S.L.J.]), AstraZeneca, and the National Institute of Health Research Biomedical Research Centre and Clinical Lecturer funding schemes. |
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| Disclosure of potential conflict of interest: A. Sykes receives research support from AstraZeneca. M. McHale is a shareholder in AstraZeneca Pharmaceuticals and is a founder of and a shareholder in ASLAN Pharmaceuticals. S. L. Johnston has consultant arrangements and a share option with Centocor; has consultant arrangements with Sanofi-Pasteur, Synairgen, GlaxoSmithKline, Chiesi, Boehringer Ingelheim, Grunenthal, and Novartis; and receives research support from the European Research Council (ERS) FP7, the Medical Research Council Clinical Research Fellowship, the National Institute of Health Research, Asthma UK, the Medical Research Council, Predicta FP7 Collaborative Project, the Wellcome Trust–sponsored Centre for Respiratory Infection, the British Lung Foundation, and AstraZeneca. |
Vol 129 - N° 6
P. 1506 - juin 2012 Retour au numéro
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