Human Rhinovirus Infection of Epithelial Cells Modulates Airway Smooth Muscle Migration

Shariff, Sami; Shelfoon, Christopher; Holden, Neil S.; Traves, Suzanne L.; Wiehler, Shahina; Kooi, Cora; Leigh, Richard

doi:10.1165/rcmb.2016-0252oc

Cited by 33 publications

(30 citation statements)

References 38 publications

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“…106 Finally, RVs can contribute to airway remodeling by inducing vascular endothelial growth factor, TGF-b, and chemoattractants for airway smooth muscle cells. 107,108 These effects might be more pronounced for RV infections in early life. 109 Thus repeated RV infections that extend to the lower airways could damage the airways and lead to remodeling of airway structures.…”

Section: Mechanisms Linking Rv-induced Wheezing To Asthma Developmentmentioning

confidence: 99%

Role of viral infections in the development and exacerbation of asthma in children

Jartti

Gern

2017

Journal of Allergy and Clinical Immunology

359

372

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Viral infections are closely linked to wheezing illnesses in children of all ages. Respiratory syncytial virus (RSV) is the main causative agent of bronchiolitis, whereas rhinovirus (RV) is most commonly detected in wheezing children thereafter. Severe respiratory illness induced by either of these viruses is associated with subsequent development of asthma, and the risk is greatest for young children who wheeze with RV infections. Whether viral illnesses actually cause asthma is the subject of intense debate. RSV-induced wheezing illnesses during infancy influence respiratory health for years. There is definitive evidence that RSV-induced bronchiolitis can damage the airways to promote airway obstruction and recurrent wheezing. RV likely causes less structural damage and yet is a significant contributor to wheezing illnesses in young children and in the context of asthma. For both viruses, interactions between viral virulence factors, personal risk factors (eg, genetics), and environmental exposures (eg, airway microbiome) promote more severe wheezing illnesses and the risk for progression to asthma. In addition, allergy and asthma are major risk factors for more frequent and severe RV-related illnesses. Treatments that inhibit inflammation have efficacy for RV-induced wheezing, whereas the anti-RSV mAb palivizumab decreases the risk of severe RSV-induced illness and subsequent recurrent wheeze. Developing a greater understanding of personal and environmental factors that promote more severe viral illnesses might lead to new strategies for the prevention of viral wheezing illnesses and perhaps reduce the subsequent risk for asthma.

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Section: Mechanisms Linking Rv-induced Wheezing To Asthma Developmentmentioning

confidence: 99%

Role of viral infections in the development and exacerbation of asthma in children

Jartti

Gern

2017

Journal of Allergy and Clinical Immunology

359

372

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“…Pooled HBE supernatants were diluted 1:10 in neutrophil resuspension medium. Neutrophil migration over a 1-h period was assessed using a modified Boyden chamber (NeuroProbe, Cabin John, MD) as described (21,31).…”

Section: Neutrophil Isolation and Recruitment Assaymentioning

confidence: 99%

Rhinovirus and Bacteria Synergistically Induce IL-17C Release from Human Airway Epithelial Cells To Promote Neutrophil Recruitment

Jamieson

Traves

Kooi

et al. 2019

The Journal of Immunology

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Virus-bacteria coinfections are associated with more severe exacerbations and increased risk of hospital readmission in patients with chronic obstructive pulmonary disease (COPD). The airway epithelium responds to such infections by releasing proinflammatory and antimicrobial cytokines, including IL-17C. However, the regulation and role of IL-17C is not well understood. In this study, we examine the mechanisms regulating IL-17C production and its potential role in COPD exacerbations. Human bronchial epithelial cells (HBE) obtained from normal, nontransplanted lungs or from brushings of nonsmokers, healthy smokers, or COPD patients were exposed to bacteria and/or human rhinovirus (HRV). RNA and protein were collected for analysis, and signaling pathways were assessed with pharmacological agonists, inhibitors, or small interfering RNAs. HBE were also stimulated with IL-17C to assess function. HRV-bacterial coinfections synergistically induced IL-17C expression. This induction was dependent on HRV replication and required NF-kB-mediated signaling. Synergy was lost in the presence of an inhibitor of the p38 MAP kinase pathway. HBE exposed to IL-17C show increased gene expression of CXCL1, CXCL2, NFKBIZ, and TFRC, and release CXCL1 protein, a neutrophil chemoattractant. Knockdown of IL-17C significantly reduced induction of CXCL1 in response to HRV-bacterial coinfection as well as neutrophil chemotaxis. HBE from healthy smokers release less IL-17C than cells from nonsmokers, but cells from COPD patients release significantly more IL-17C compared with either nonsmokers or healthy smokers. These data suggest that IL-17C may contribute to microbial-induced COPD exacerbations by promoting neutrophil recruitment.

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“…Airway epithelial cells are the primary site of RV infection and replication, and release cytokines that orchestrate downstream responses [13][14][15][16] . It has previously been shown that bronchial epithelial cells (BECs) from asthma cases and non-asthma controls have different transcriptional and cytokine responses to RV in cell culture [17][18][19][20][21] .…”

mentioning

confidence: 99%

Altered transcriptional and chromatin responses to rhinovirus in bronchial epithelial cells from adults with asthma

et al. 2020

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There is a life-long relationship between rhinovirus (RV) infection and the development and clinical manifestations of asthma. In this study we demonstrate that cultured primary bronchial epithelial cells from adults with asthma (n = 9) show different transcriptional and chromatin responses to RV infection compared to those without asthma (n = 9). Both the number and magnitude of transcriptional and chromatin responses to RV were muted in cells from asthma cases compared to controls. Pathway analysis of the transcriptionally responsive genes revealed enrichments of apoptotic pathways in controls but inflammatory pathways in asthma cases. Using promoter capture Hi-C we tethered regions of RV-responsive chromatin to RV-responsive genes and showed enrichment of these regions and genes at asthma GWAS loci. Taken together, our studies indicate a delayed or prolonged inflammatory state in cells from asthma cases and highlight genes that may contribute to genetic risk for asthma.

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Human Rhinovirus Infection of Epithelial Cells Modulates Airway Smooth Muscle Migration

Cited by 33 publications

References 38 publications

Role of viral infections in the development and exacerbation of asthma in children

Role of viral infections in the development and exacerbation of asthma in children

Rhinovirus and Bacteria Synergistically Induce IL-17C Release from Human Airway Epithelial Cells To Promote Neutrophil Recruitment

Altered transcriptional and chromatin responses to rhinovirus in bronchial epithelial cells from adults with asthma

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