Cigarette Smoke Modulates Expression of Human Rhinovirus-Induced Airway Epithelial Host Defense Genes

Proud, David; Hudy, Magdalena H.; Wiehler, Shahina; Zaheer, Raza S.; Amin, Minaa A.; Pelikan, Jonathan B.; Tacon, Claire E.; Tonsaker, Tabitha; Walker, Brandie; Kooi, Cora; Traves, Suzanne L.; Leigh, Richard

doi:10.1371/journal.pone.0040762

Cited by 60 publications

(75 citation statements)

References 39 publications

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“…IFN protein has been observed to vary with different RV subtypes and much lower levels of RV16-induced IFN-β protein have been reported6 19 since the original report 7. Other investigators have failed to detect RV16-induced IFN-β protein production despite significant mRNA induction,4 22 suggesting that bronchial epithelial cells may vary in their response to RV infection.…”

Section: Discussionmentioning

confidence: 99%

Rhinovirus-induced interferon production is not deficient in well controlled asthma

Sykes

Macintyre

Edwards

et al. 2013

Thorax

119

110

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Background Defective rhinovirus (RV)-induced interferon (IFN)-β and IFN-λ production and increased RV replication have been reported in primary human bronchial epithelial cells (HBECs) from subjects with asthma. How universal this defect is in asthma is unknown. Additionally, the IFN subtypes induced by RV infection in primary HBECs have not been comprehensively investigated. Objective To study RV induction of IFN-α, IFN-β and IFN-λ and RV replication in HBECs from subjects with atopic asthma and healthy controls. Methods HBECs were obtained from subjects with asthma and healthy controls and infected with RV16 and RV1B, and cells and supernatants harvested at 8, 24 and 48h. IFN proteins were analysed by ELISA and IFN mRNA and viral RNA expression by quantitative PCR. Virus release was assessed in cell supernatants. Results IFN-β and IFN-λ were the only IFNs induced by RV in HBECs and IFN-λ protein induction was substantially greater than IFN-β. Induction of IFN-λ1 mRNA by RV16 at 48h was significantly greater in HBECs from subjects with asthma; otherwise there were no significant differences between subjects with asthma and controls in RV replication, or in induction of type I or III IFN protein or mRNA. Conclusions IFN-λ and, to a lesser degree, IFN-β are the major IFN subtypes induced by RV infection of HBECs. Neither defective IFN induction by RV nor increased RV replication was observed in the HBECs from subjects with well controlled asthma reported in this study.

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Section: Discussionmentioning

confidence: 99%

Rhinovirus-induced interferon production is not deficient in well controlled asthma

Sykes

Macintyre

Edwards

et al. 2013

Thorax

119

110

View full text Add to dashboard Cite

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“…Human RV-16 was propagated as described 23 . Bronchial epithelial cells were exposed to HRV-16 at 10 5.5 50% tissue culture-infective dose (TCID 50 ) U/ml (MOI of ~1) 24 .…”

Section: Methodsmentioning

confidence: 99%

Rhinovirus infection interferes with induction of tolerance to aeroantigens through OX40 ligand, thymic stromal lymphopoietin, and IL-33

Mehta

Duan

Doerner

et al. 2016

Journal of Allergy and Clinical Immunology

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Background Rhinovirus (RV) infection during an early age has been associated with development of asthma, but how RV influences the immune response is not clear. Objective Tolerance to inhaled antigen is mediated via the induction of regulatory T cells (Treg), and we asked whether RV infection of the respiratory tract might block airway tolerance by modulating Treg cells. Methods The immune response to intranasal ovalbumin (OVA) in mice was assessed with concomitant infection with RV1B, and the factors induced in vivo were compared to factors made by human lung epithelial cells infected in vitro with RV16. Results RV1B infection of mice abrogated tolerance induced by inhalation of soluble OVA, suppressing the normal generation of Foxp3+ Treg cells while promoting Th2 cells. Furthermore, RV1B infection led to susceptibility to develop asthmatic lung disease when mice subsequently reencountered aeroantigen. RV1B promoted early in vivo expression of the TNF family protein, OX40L, on lung dendritic cells that was dependent on the innate cytokine thymic stromal lymphopoietin (TSLP), and also induced another innate cytokine IL-33. Inhibiting each of these pathways allowed the natural development of Treg cells while minimizing Th2 differentiation, and restored tolerance in the face of RV1B infection. In accordance, RV16 infection of human lung epithelial cells upregulated TSLP and IL-33 expression. Conclusions These results suggest that infection of the respiratory epithelium with RV can antagonize tolerance to inhaled antigen through a combined induction of TSLP, IL-33 and OX40L, and this may lead to susceptibility to developing asthmatic lung inflammation.

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“…In COPD and smokers without COPD, a variety of studies have shown that cigarette smoke exposure impairs host defence by decreasing epithelial barrier function, ciliary function, antimicrobial peptide production and antiviral responses, while increasing mucus production (59;76;89). Cigarette smoke is the main risk factor for development of COPD, and many of these epithelial features of COPD can be explained by a direct or indirect result of cigarette smoke exposure.…”

Section: Epithelial Cell (Dys)function In Inflammatory Lung Diseasesmentioning

confidence: 99%

The innate immune function of airway epithelial cells in inflammatory lung disease

2015

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The airway epithelium is now considered central to the orchestration of pulmonary inflammatory and immune responses, and is also key to tissue remodelling. It acts as a first barrier in the defence against a wide range of inhaled challenges, and is critically involved in the regulation of both innate and adaptive immune responses to these challenges. Recent progress in our understanding of the developmental regulation of this tissue, the differentiation pathways, recognition of pathogens and antimicrobial responses is now exploited to help understand how epithelial cell function and dysfunction contributes to the pathogenesis of a variety of inflammatory lung diseases. In the review, advances in our knowledge of the biology of airway epithelium, as well as its role and (dys)function in asthma, COPD and cystic fibrosis, are discussed.

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Cigarette Smoke Modulates Expression of Human Rhinovirus-Induced Airway Epithelial Host Defense Genes

Cited by 60 publications

References 39 publications

Rhinovirus-induced interferon production is not deficient in well controlled asthma

Rhinovirus-induced interferon production is not deficient in well controlled asthma

Rhinovirus infection interferes with induction of tolerance to aeroantigens through OX40 ligand, thymic stromal lymphopoietin, and IL-33

The innate immune function of airway epithelial cells in inflammatory lung disease

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