title: Role of deficient type III interferon-lambda production in asthma exacerbations.
abstract: 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-lambdas 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.
authors.affiliation: Department of Respiratory Medicine, National Heart and Lung Institute, Imperial College London, Norfolk Place, London W2 1PG, UK.
authors.forename: Marco
authors.initials: M
authors.lastname: Contoli
authors.forename: Simon D
authors.initials: SD
authors.lastname: Message
authors.forename: Vasile
authors.initials: V
authors.lastname: Laza-Stanca
authors.forename: Michael R
authors.initials: MR
authors.lastname: Edwards
authors.forename: Peter A B
authors.initials: PA
authors.lastname: Wark
authors.forename: Nathan W
authors.initials: NW
authors.lastname: Bartlett
authors.forename: Tatiana
authors.initials: T
authors.lastname: Kebadze
authors.forename: Patrick
authors.initials: P
authors.lastname: Mallia
authors.forename: Luminita A
authors.initials: LA
authors.lastname: Stanciu
authors.forename: Hayley L
authors.initials: HL
authors.lastname: Parker
authors.forename: Louise
authors.initials: L
authors.lastname: Slater
authors.forename: Anita
authors.initials: A
authors.lastname: Lewis-Antes
authors.forename: Onn M
authors.initials: OM
authors.lastname: Kon
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Holgate
authors.forename: Donna E
authors.initials: DE
authors.lastname: Davies
authors.forename: Sergei V
authors.initials: SV
authors.lastname: Kotenko
authors.forename: Alberto
authors.initials: A
authors.lastname: Papi
authors.forename: Sebastian L
authors.initials: SL
authors.lastname: Johnston
mesh_terms: D001249:Asthma / Q000150:complications / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D010850:Picornaviridae Infections / Q000150:complications*; D012229:Rhinovirus / Q000378:metabolism*; D000095022:Interferon Lambda
chemical_list: D016207:Cytokines; D007372:Interferons; D007378:Interleukins; D008070:Lipopolysaccharides; C000624353:interferon-lambda, human; D000095022:Interferon Lambda