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-λs 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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Corne, J.M. et al. Lancet 359, 831–834 (2002).
Talbot, T.R. et al. N. Engl. J. Med. 352, 2082–2090 (2005).
Wark, P. et al. J. Exp. Med. 201, 937–947 (2005).
Kotenko, S.V. et al. Nat. Immunol. 4, 69–77 (2003).
Sheppard, P. et al. Nat. Immunol. 4, 63–68 (2003).
Spann, K.M., Tran, K.C., Chi, B., Rabin, R.L. & Collins, P.L. J. Virol. 78, 4363–4369 (2004).
Johnston, S.L. et al. Br. Med. J. 310, 1225–1229 (1995).
Johnston, S.L. et al. N. Engl. J. Med. 354, 1589–1600 (2006).
Yoneyama, M. et al. Nat. Immunol. 5, 730–737 (2004).
Carr, D.J., Tomanek, L., Silverman, R.H., Campbell, I.L. & Williams, B.R. J. Virol. 79, 9341–9345 (2005).
Yang, K. et al. Immunity 23, 465–478 (2005).
Hewson, C.A., Jardine, A., Edwards, M.R., Laza-Stanca, V. & Johnston, S.L. J. Virol. 79, 12273–12279 (2005).
Fitzgerald, K.A. et al. J. Exp. Med. 198, 1043–1055 (2003).
Illi, S. et al. Br. Med. J. 322, 390–395 (2001).
M.C. was the recipient of a European Respiratory Society fellowship (LTRF2003-017). P.A.B.W. was supported by the National Health and Medical Research Council Australia Neil Hamilton Fairley Fellowship. This work was supported by the Medical Research Council, UK: Clinical Research Professorship (to S.T.H.) & Clinical Research Fellowship (to S.D.M. and S.L.J.), British Medical Association HC Roscoe Fellowships (to P.A.B.W. and S.D.M.), Asthma UK grant numbers 05/067 (to S.L.J.) and 03/031 (to P.A.B.W., D.E.D. and S.T.H.), United States Public Health Services Grants AI051139 and AI057468 from the National Institute of Allergy and Infectious Diseases (to S.V.K.) and by British Lung Foundation/Severin Wunderman Family Foundation Programme Grant 00/02 (to S.L.J.).
Stephen T. Holgate and Donna E. Davies were cofounders of, hold shares in and are consultants for, and Sebastian L. Johnston is a consultant for Synairgen PLC, which has an interest in developing interferons for treating respiratory diseases. Sebastian L. Johnston, Stephen T. Holgate, Donna E. Davies, Peter A.B. Wark and Sergei V. Kotenko are inventors on patents relating to the use of interferons for treating respiratory diseases.
IFN-λs are induced by rhinovirus infection of bronchial epithelial cells, monocytes and macrophages. (PDF 810 kb)
IFN-λs induce IFN-stimulated genes in and protect bronchial epithelial cells against rhinovirus infection in vitro. (PDF 636 kb)
Demographic data for patients entering the clinical studies. (PDF 45 kb)
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