Role of deficient type III interferon-lambda production in asthma exacerbations.
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.
Contoli
Marco
M
Department of Respiratory Medicine, National Heart and Lung Institute, Imperial College London, Norfolk Place, London W2 1PG, UK.
Message
Simon D
SD
Laza-Stanca
Vasile
V
Edwards
Michael R
MR
Wark
Peter A B
PA
Bartlett
Nathan W
NW
Kebadze
Tatiana
T
Mallia
Patrick
P
Stanciu
Luminita A
LA
Parker
Hayley L
HL
Slater
Louise
L
Lewis-Antes
Anita
A
Kon
Onn M
OM
Holgate
Stephen T
ST
Davies
Donna E
DE
Kotenko
Sergei V
SV
Papi
Alberto
A
Johnston
Sebastian L
SL
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
D016207:Cytokines; D007372:Interferons; D007378:Interleukins; D008070:Lipopolysaccharides; C000624353:interferon-lambda, human; D000095022:Interferon Lambda