Impaired innate interferon induction in severe therapy resistant atopic asthmatic children

被引：176

作者：

Edwards, M. R. ^{[1
,2
,3
]}

Regamey, N. ^{[4
,5
,6
]}

Vareille, M. ^{[4
,5
,6
]}

Kieninger, E. ^{[4
,5
,6
]}

Gupta, A. ^{[2
,7
]}

Shoemark, A. ^{[2
,7
]}

Saglani, S. ^{[2
,7
]}

Sykes, A. ^{[1
,2
,3
]}

Macintyre, J. ^{[1
,2
,3
]}

Davies, J. ^{[2
,7
]}

Bossley, C. ^{[2
,7
]}

Bush, A. ^{[2
,7
]}

Johnston, S. L. ^{[1
,2
,3
]}

机构：

[1] Natl Heart Lung Inst, London, England

[2] MRC & Asthma UK Ctr Allerg Mech Asthma, London, England

[3] Univ London Imperial Coll Sci Technol & Med, Ctr Resp Infect, London, England

[4] Univ Hosp Bern, Div Paediat Resp Med, Dept Paediat, CH-3010 Bern, Switzerland

[5] Univ Hosp Bern, Dept Clin Res, Inselspital, CH-3010 Bern, Switzerland

[6] Univ Bern, Bern, Switzerland

[7] Univ London Imperial Coll Sci Technol & Med, Royal Brompton NHS Trust, London, England

来源：

MUCOSAL IMMUNOLOGY | 2013年 / 6卷 / 04期

基金：

英国惠康基金;

关键词：

BRONCHIAL EPITHELIAL-CELLS; RHINOVIRUS INFECTION; ANTIVIRAL RESPONSES; EXACERBATIONS; BUDESONIDE; EXPRESSION; DEFICIENT; ALPHA; BETA; CYTOKINE;

D O I：

10.1038/mi.2012.118

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Deficient type I interferon-beta and type III interferon-lambda induction by rhinoviruses has previously been reported in mild/moderate atopic asthmatic adults. No studies have yet investigated if this occurs in severe therapy resistant asthma (STRA). Here, we show that compared with non-allergic healthy control children, bronchial epithelial cells cultured ex vivo from severe therapy resistant atopic asthmatic children have profoundly impaired interferon-beta and interferon-lambda mRNA and protein in response to rhinovirus (RV) and polyIC stimulation. Severe treatment resistant asthmatics also exhibited increased virus load, which negatively correlated with interferon mRNA levels. Furthermore, uninfected cells from severe therapy resistant asthmatic children showed lower levels of Toll-like receptor-3 mRNA and reduced retinoic acid inducible gene and melanoma differentiation-associated gene 5 mRNA after RV stimulation. These data expand on the original work, suggesting that the innate anti-viral response to RVs is impaired in asthmatic tissues and demonstrate that this is a feature of STRA.

引用

页码：797 / 806

页数：10

共 47 条

[1]

Baraldo S., 2012, J ALLERGY C IN PRESS

[2]

Diagnosis and definition of severe refractory asthma: an international consensus statement from the Innovative Medicine Initiative (IMI) [J].