Airway Epithelial Cell Immunity Is Delayed During Rhinovirus Infection in Asthma and COPD

Veerati, Punnam Chander; Troy, Niamh M.; Reid, Andrew T; Li, Ngan Fung; Nichol, Kristy S; Kaur, Parwinder; Maltby, Steven; Wark, Peter; Knight, Darryl A.; Bosco, Anthony; Grainge, Christopher; Bartlett, Nathan W.

doi:10.3389/fimmu.2020.00974

Cited by 69 publications

(94 citation statements)

References 57 publications

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“…Regardless of the virus strain and cellular model used in this study, BECs from COPD subjects were not more susceptible to infection than healthy BECs. This is consistent with other studies in which either submerged [ 17 ] or WD [ 18 ] BECs from asthmatic or COPD patients were exposed to RV-1B or RV-A1, respectively, and viral replication quantified up to 7 days p.i. In contrast, an earlier study, also using WD-BECs infected with RV-39, demonstrated elevated virus replication in COPD cells compared to healthy cells 24 and 48 h.p.i.…”

Section: Discussionsupporting

confidence: 91%

“…The main driver for IFN-β as a treatment is evidence that COPD is associated with reduced IFN-β and/or IFN-λ production, making individuals more susceptible to viral infections [ 15 , 16 ]. However, not all studies agree [ 14 , 17 ], and a recent study has demonstrated delayed rather than reduced IFN responses by infected primary bronchial epithelial cells (BECs) from COPD patients [ 18 ]. Although several viruses induce exacerbation, in vitro investigations of the IFN response in COPD have primarily utilised IFV or RV.…”

Section: Introductionmentioning

confidence: 99%

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COPD Is Associated with Elevated IFN-β Production by Bronchial Epithelial Cells Infected with RSV or hMPV

Collinson

Snape

Beagley

et al. 2021

Viruses

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IFN treatment may be a viable option for treating COPD exacerbations based on evidence of IFN deficiency in COPD. However, in vitro studies have used primarily influenza and rhinoviruses to investigate IFN responses. This study aims to investigate the susceptibility to infection and IFN response of primary bronchial epithelial cells (BECs) from COPD donors to infection with RSV and hMPV. BECs from five COPD and five healthy donors were used to establish both submerged monolayer and well-differentiated (WD) cultures. Two isolates of both RSV and hMPV were used to infect cells. COPD was not associated with elevated susceptibility to infection and there was no evidence of an intrinsic defect in IFN production in either cell model to either virus. Conversely, COPD was associated with significantly elevated IFN-β production in response to both viruses in both cell models. Only in WD-BECs infected with RSV was elevated IFN-β associated with reduced viral shedding. The role of elevated epithelial cell IFN-β production in the pathogenesis of COPD is not clear and warrants further investigation. Viruses vary in the responses that they induce in BECs, and so conclusions regarding antiviral responses associated with disease cannot be made based on single viral infections.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

COPD Is Associated with Elevated IFN-β Production by Bronchial Epithelial Cells Infected with RSV or hMPV

Collinson

Snape

Beagley

et al. 2021

Viruses

View full text Add to dashboard Cite

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“…Based on these results, the authors postulated that the second peak appeared due to the production of new virus, after the eclipse caused by the innate immune system ( 102 ). Similar replication kinetics and cytokines were seen in other studies, including type I and type III IFN ( 103 , 104 , 174 , 175 ). In one study it was shown that upon HRV infection IL-17C was produced in the basolateral compartment and induced CXLC1, which is a neutrophil attractant and may contribute to exacerbations of lower airway disease ( 103 ).…”

Section: Discussionsupporting

confidence: 86%

In Vitro Modelling of Respiratory Virus Infections in Human Airway Epithelial Cells – A Systematic Review

et al. 2021

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Respiratory tract infections (RTI) are a major cause of morbidity and mortality in humans. A large number of RTIs is caused by viruses, often resulting in more severe disease in infants, elderly and the immunocompromised. Upon viral infection, most individuals experience common cold-like symptoms associated with an upper RTI. However, in some cases a severe and sometimes life-threatening lower RTI may develop. Reproducible and scalable in vitro culture models that accurately reflect the human respiratory tract are needed to study interactions between respiratory viruses and the host, and to test novel therapeutic interventions. Multiple in vitro respiratory cell culture systems have been described, but the majority of these are based on immortalized cell lines. Although useful for studying certain aspects of viral infections, such monomorphic, unicellular systems fall short in creating an understanding of the processes that occur at an integrated tissue level. Novel in vitro models involving primary human airway epithelial cells and, more recently, human airway organoids, are now in use. In this review, we describe the evolution of in vitro cell culture systems and their characteristics in the context of viral RTIs, starting from advances after immortalized cell cultures to more recently developed organoid systems. Furthermore, we describe how these models are used in studying virus-host interactions, e.g. tropism and receptor studies as well as interactions with the innate immune system. Finally, we provide an outlook for future developments in this field, including co-factors that mimic the microenvironment in the respiratory tract.

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“…In other words, in host protection the level of IFN type I expression depends on the time after the infection and the amount of RV infecting the host. 24-48h hours after the infection is the highest peak of viral RNA detectable, while the viral titer was the highest after 24-72 hours (46).…”

Section: Interferon Type I and Its Signalingmentioning

confidence: 93%

Mechanism of Rhinovirus Immunity and Asthma

et al. 2021

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The majority of asthma exacerbations in children are caused by Rhinovirus (RV), a positive sense single stranded RNA virus of the Picornavirus family. The host has developed virus defense mechanisms that are mediated by the upregulation of interferon-activated signaling. However, the virus evades the immune system by inducing immunosuppressive cytokines and surface molecules like programmed cell death protein 1 (PD-1) and its ligand (PD-L1) on immunocompetent cells. Initially, RV infects epithelial cells, which constitute a physiologic mucosal barrier. Upon virus entrance, the host cell immediately recognizes viral components like dsRNA, ssRNA, viral glycoproteins or CpG-DNA by host pattern recognition receptors (PRRs). Activation of toll like receptors (TLR) 3, 7 and 8 within the endosome and through MDA-5 and RIG-I in the cytosol leads to the production of interferon (IFN) type I and other antiviral agents. Every cell type expresses IFNAR1/IFNAR2 receptors thus allowing a generalized antiviral activity of IFN type I resulting in the inhibition of viral replication in infected cells and preventing viral spread to non-infected cells. Among immune evasion mechanisms of the virus, there is downregulation of IFN type I and its receptor as well as induction of the immunosuppressive cytokine TGF-β. TGF-β promotes viral replication and is associated with induction of the immunosuppression signature markers LAP3, IDO and PD-L1. This article reviews the recent advances on the regulation of interferon type I expression in association with RV infection in asthmatics and the immunosuppression induced by the virus.

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Airway Epithelial Cell Immunity Is Delayed During Rhinovirus Infection in Asthma and COPD

Cited by 69 publications

References 57 publications

COPD Is Associated with Elevated IFN-β Production by Bronchial Epithelial Cells Infected with RSV or hMPV

COPD Is Associated with Elevated IFN-β Production by Bronchial Epithelial Cells Infected with RSV or hMPV

In Vitro Modelling of Respiratory Virus Infections in Human Airway Epithelial Cells – A Systematic Review

Mechanism of Rhinovirus Immunity and Asthma

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