BibTex format
@article{Singanayagam:2018:10.1038/s41467-018-04574-1,
author = {Singanayagam, A and Glanville, N and Girkin, J and Ching, YM and Marcellini, A and Porter, J and Toussaint, M and Walton, R and Finney, L and Julia, A and Zhu, J and Trujillo-Torralbo, M and Calderazzo, M and Grainge, C and Loo, S-L and Veerati, PC and Pathinayake, P and Nichol, K and Reid, A and James, P and Solari, R and Wark, P and Knight, D and Moffatt, M and Cookson, W and Edwards, M and Mallia, P and Bartlett, N and Johnston, SL},
doi = {10.1038/s41467-018-04574-1},
journal = {Nature Communications},
pages = {1--16},
title = {Corticosteroid suppression of antiviral immunity increases bacterial loads and mucus production in COPD exacerbations},
url = {http://dx.doi.org/10.1038/s41467-018-04574-1},
volume = {9},
year = {2018}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Inhaled corticosteroids (ICS) have limited efficacy in reducing chronic obstructive pulmonary disease (COPD) exacerbations and increase pneumonia risk, through unknown mechanisms. Rhinoviruses precipitate most exacerbations and increase susceptibility to secondary bacterial infections. Here, we show that the ICS fluticasone propionate (FP) impairs innate and acquired antiviral immune responses leading to delayed virus clearance and previously unrecognised adverse effects of enhanced mucus, impaired antimicrobial peptide secretion and increased pulmonary bacterial load during virus-induced exacerbations. Exogenous interferon-β reverses these effects. FP suppression of interferon may occur through inhibition of TLR3- and RIG-I virus-sensing pathways. Mice deficient in the type I interferon-α/β receptor (IFNAR1−/−) have suppressed antimicrobial peptide and enhanced mucin responses to rhinovirus infection. This study identifies type I interferon as a central regulator of antibacterial immunity and mucus production. Suppression of interferon by ICS during virus-induced COPD exacerbations likely mediates pneumonia risk and raises suggestion that inhaled interferon-β therapy may protect.
AU - Singanayagam,A
AU - Glanville,N
AU - Girkin,J
AU - Ching,YM
AU - Marcellini,A
AU - Porter,J
AU - Toussaint,M
AU - Walton,R
AU - Finney,L
AU - Julia,A
AU - Zhu,J
AU - Trujillo-Torralbo,M
AU - Calderazzo,M
AU - Grainge,C
AU - Loo,S-L
AU - Veerati,PC
AU - Pathinayake,P
AU - Nichol,K
AU - Reid,A
AU - James,P
AU - Solari,R
AU - Wark,P
AU - Knight,D
AU - Moffatt,M
AU - Cookson,W
AU - Edwards,M
AU - Mallia,P
AU - Bartlett,N
AU - Johnston,SL
DO - 10.1038/s41467-018-04574-1
EP - 16
PY - 2018///
SN - 2041-1723
SP - 1
TI - Corticosteroid suppression of antiviral immunity increases bacterial loads and mucus production in COPD exacerbations
T2 - Nature Communications
UR - http://dx.doi.org/10.1038/s41467-018-04574-1
UR - https://www.nature.com/articles/s41467-018-04574-1
UR - http://hdl.handle.net/10044/1/60020
VL - 9
ER -