TLR3, TLR4 and TLRs7-9 Induced Interferons Are Not Impaired in Airway and Blood Cells in Well Controlled Asthma

被引:37
作者
Sykes, Annemarie [1 ,2 ,3 ,4 ,5 ]
Edwards, Michael R. [1 ,2 ,3 ,4 ]
Macintyre, Jonathan [1 ,2 ,3 ,4 ,5 ]
del Rosario, Ajerico [1 ,2 ,3 ,4 ,5 ]
Gielen, Vera [1 ,2 ,3 ,4 ]
Haas, Jennifer [1 ,2 ,3 ,4 ]
Kon, Onn Min [5 ]
McHale, Mark [6 ]
Johnston, Sebastian L. [1 ,2 ,3 ,4 ,5 ]
机构
[1] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England
[2] MRC, London, England
[3] Asthma UK Ctr Allerg Mech Asthma, London, England
[4] Univ London Imperial Coll Sci Technol & Med, Ctr Resp Infect, London, England
[5] Imperial Coll Healthcare NHS Trust, London, England
[6] AstraZeneca R&D Charnwood, Resp & Inflammat Res Area, Loughborough, Leics, England
基金
英国医学研究理事会; 英国惠康基金;
关键词
INVASIVE PNEUMOCOCCAL DISEASE; BRONCHIAL EPITHELIAL-CELLS; MONONUCLEAR-CELLS; RHINOVIRUS; INFECTION; DEFICIENT; RESPONSES; CHILDREN; AGONISTS; ALPHA;
D O I
10.1371/journal.pone.0065921
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Defective Rhinovirus induced interferon-beta and interferon-lambda production has been reported in bronchial epithelial cells from asthmatics but the mechanisms of defective interferon induction in asthma are unknown. Virus infection can induce interferon through Toll like Receptors (TLR) 3, TLR7 and TLR8. The role of these TLRs in interferon induction in asthma is unclear. This objective of this study was to measure the type I and III interferon response to TLR in bronchial epithelial cells and peripheral blood cells from atopic asthmatics and non-atopic non-asthmatics. Bronchial epithelial cells and peripheral blood mononuclear cells from atopic asthmatic and non-atopic non-asthmatic subjects were stimulated with agonists to TLR3, TLR4 & TLRs7-9 and type I and III interferon and pro-inflammatory cytokine, interleukin(IL)-6 and IL-8, responses assessed. mRNA expression was analysed by qPCR. Interferon proteins were analysed by ELISA. Pro-inflammatory cytokines were induced by each TLR ligand in both cell types. Ligands to TLR3 and TLR7/8, but not other TLRs, induced interferon-beta and interferon-lambda in bronchial epithelial cells. The ligand to TLR7/8, but not those to other TLRs, induced only type I interferons in peripheral blood mononuclear cells. No difference was observed in TLR induced interferon or pro-inflammatory cytokine production between asthmatic and non-asthmatic subjects from either cell type. TLR3 and TLR7/8,, stimulation induced interferon in bronchial epithelial cells and peripheral blood mononuclear cells. Interferon induction to TLR agonists was not observed to be different in asthmatics and non-asthmatics.
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页数:10
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共 32 条
[1]   Synthetic agonists of Toll-like receptors 7, 8 and 9 [J].
Agrawal, S. ;
Kandimalla, E. R. .
BIOCHEMICAL SOCIETY TRANSACTIONS, 2007, 35 :1461-1467
[2]   Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3 [J].
Alexopoulou, L ;
Holt, AC ;
Medzhitov, R ;
Flavell, RA .
NATURE, 2001, 413 (6857) :732-738
[3]   Increased frequency of detection of Chiamydophila pneumoniae in asthma [J].
Biscione, GL ;
Corne, J ;
Chauhan, AJ ;
Johnston, SL .
EUROPEAN RESPIRATORY JOURNAL, 2004, 24 (05) :745-749
[4]   Atopic phenotype in children is associated with decreased virus-induced interferon-α release [J].
Bufe, A ;
Gehlhar, K ;
Grage-Griebenow, E ;
Ernst, M .
INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY, 2002, 127 (01) :82-88
[5]   Role of deficient type III interferon-λ production in asthma exacerbations [J].
Contoli, Marco ;
Message, Simon D. ;
Laza-Stanca, Vasile ;
Edwards, Michael R. ;
Wark, Peter A. B. ;
Bartlett, Nathan W. ;
Kebadze, Tatiana ;
Mallia, Patrick ;
Stanciu, Luminita A. ;
Parker, Hayley L. ;
Slater, Louise ;
Lewis-Antes, Anita ;
Kon, Onn M. ;
Holgate, Stephen T. ;
Davies, Donna E. ;
Kotenko, Sergei V. ;
Papi, Alberto ;
Johnston, Sebastian L. .
NATURE MEDICINE, 2006, 12 (09) :1023-1026
[6]   Frequency, severity, and duration of rhinovirus infections in asthmatic and non-asthmatic individuals: a longitudinal cohort study [J].
Corne, JM ;
Marshall, C ;
Smith, S ;
Schreiber, J ;
Sanderson, G ;
Holgate, ST ;
Johnston, SL .
LANCET, 2002, 359 (9309) :831-834
[7]   Impaired type I and III interferon response to rhinovirus infection during pregnancy and asthma [J].
Forbes, Rebecca Louise ;
Gibson, Peter G. ;
Murphy, Vanessa E. ;
Wark, Peter A. B. .
THORAX, 2012, 67 (03) :209-214
[8]   Impaired virus-induced interferon-α2 release in adult asthmatic patients [J].
Gehlhar, K ;
Bilitewski, C ;
Reinitz-Rademacher, K ;
Rohde, G ;
Bufe, A .
CLINICAL AND EXPERIMENTAL ALLERGY, 2006, 36 (03) :331-337
[9]   Counterregulation between the FcεRI Pathway and Antiviral Responses in Human Plasmacytoid Dendritic Cells [J].
Gill, Michelle A. ;
Bajwa, Gagan ;
George, Tiffany A. ;
Dong, Caroline C. ;
Dougherty, Irene I. ;
Jiang, Nan ;
Gan, Vanthaya N. ;
Gruchalla, Rebecca S. .
JOURNAL OF IMMUNOLOGY, 2010, 184 (11) :5999-6006
[10]   Synthetic TLR Agonists reveal functional differences between human TLR7 and TLR8 [J].
Gorden, KB ;
Gorski, KS ;
Gibson, SJ ;
Kedl, RM ;
Kieper, WC ;
Qiu, XH ;
Tomai, MA ;
Alkan, SS ;
Vasilakos, JP .
JOURNAL OF IMMUNOLOGY, 2005, 174 (03) :1259-1268