Role of deficient type III interferon- production in asthma exacerbations

Marco Contoli^1, 2, 6, Simon D Message^1, 6, Vasile Laza-Stanca¹, Michael R Edwards¹, Peter A B Wark^1, 3, Nathan W Bartlett¹, Tatiana Kebadze¹, Patrick Mallia¹, Luminita A Stanciu¹, Hayley L Parker¹, Louise Slater¹, Anita Lewis-Antes⁴, Onn M Kon⁵, Stephen T Holgate³, Donna E Davies³, Sergei V Kotenko⁵, Alberto Papi² & Sebastian L Johnston¹

¹  Department of Respiratory Medicine, National Heart and Lung Institute, Wright Fleming Institute of Infection and Immunity & MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, Imperial College London, Norfolk Place, London W2 1PG, UK.

²  Research Centre on Asthma and COPD, Department of Clinical and Experimental Medicine, University of Ferrara, via Savonarola 9, 44100, Ferrara, Italy.

³  The Brooke Laboratories, Mailpoint 888, University of Southampton School of Medicine, Southampton General Hospital, Southampton, SO16 6YD, UK.

⁴  Department of Biochemistry & Molecular Biology, Room E-641, University of Medicine & Dentistry New Jersey - New Jersey Medical School, 185 South Orange Avenue, Newark, New Jersey 07103, USA.

⁵  St Mary's NHS Trust, Praed Street, London W2 1NY, UK.

⁶  These authors contributed equally to this work.

Rhinoviruses are the major cause of asthma exacerbations, and asthmatics have increased susceptibility to rhinovirus and risk of invasive bacterial infections. Here we show deficient induction of interferon-s by rhinovirus in asthmatic primary bronchial epithelial cells and alveolar macrophages, which was highly correlated with severity of rhinovirus-induced asthma exacerbation and virus load in experimentally infected human volunteers. Induction by lipopolysaccharide in asthmatic macrophages was also deficient and correlated with exacerbation severity. These results identify previously unknown mechanisms of susceptibility to infection in asthma and suggest new approaches to prevention and/or treatment of asthma exacerbations.

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