Type-III interferon, not type-I, is the predominant interferon induced by respiratory viruses in nasal epithelial cells

Okabayashi, Tamaki; Kojima, Takashi; Takao, Masaki; Yokota, Shinichi; Imaizumi, Tadaatsu; Tsutsumi, Hiroyuki; Himi, Tetsuo; Fujii, Nobuhiro; Sawada, Norimasa

doi:10.1016/j.virusres.2011.07.011

Cited by 129 publications

(123 citation statements)

References 39 publications

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“…Interestingly, we did not find a significant increase in the level of IFN-c following RSV infection. This is consistent with a recent study suggesting that type III IFN is the predominant IFN produced in RSVinfected nasal epithelial cells [27].…”

Section: Basal Cell Cultures Infected With Rsv Increase Secretion Of supporting

confidence: 94%

Ciliary dyskinesia is an early feature of respiratory syncytial virus infection

Smith

Kulkarni

Radhakrishnan

et al. 2013

European Respiratory Journal

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Respiratory syncytial virus is a major cause of respiratory disease. There are conflicting accounts of the response of human epithelial cells to respiratory syncytial virus and a lack of data on its effect on ciliary function. Our aim was to study the early stages of respiratory syncytial virus infection of primary human basal and ciliated cultures.Using high speed videomicroscopy, we found that ciliary beat frequency was unaffected by respiratory syncytial virus infection over 72 h; however, ciliary dyskinesia significantly increased within 24 h of infection (p,0.05). Transmission electron microscopy revealed that ultrastructural abnormalities were confined to ciliated cells, including increased cilia loss and mitochondrial damage. Confocal immunofluorescence microscopy showed that respiratory syncytial virus antigen gradually spread from the cell surface to the ciliary tip of infected cells over 3 days. Interestingly, ciliated cultures secreted fewer viruses than basal (progenitor) cell cultures and produced a chemokine response focused on recruitment of neutrophils.This study highlights differences in infection models and underscores the need to explore further the role of ciliated cells in the establishment of respiratory syncytial virus infection.Increased ciliary dyskinesia combined with ciliary loss and epithelial damage is likely to result in reduced mucociliary clearance early in the infective process. @ERSpublications Increased ciliary dyskinesia with ciliary loss and epithelial damage can result in reduced mucociliary clearance

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Section: Basal Cell Cultures Infected With Rsv Increase Secretion Of supporting

confidence: 94%

Ciliary dyskinesia is an early feature of respiratory syncytial virus infection

Smith

Kulkarni

Radhakrishnan

et al. 2013

European Respiratory Journal

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“…IFN-l was also shown to be the predominant IFN induced by IAV in the mouse lung, and a much larger burst of IFN-l was observed in an in vivo model after IAV infection (10). IFN-l receptor expression has been shown to be limited in epithelial cells (28), and IFN-l contributes to the main first-line defense against respiratory viral infections in nasal epithelial cells via the retinoic acid-inducible gene-1-dependent pathway (31). Taking these findings together, IFN-l has been demonstrated to play a newly discovered role in protecting respiratory and nasal epithelia from viral infection, and IFN-l provides an IFN-b induction-independent therapeutic strategy against viral infection.…”

Section: Discussionmentioning

confidence: 99%

Reactive Oxygen Species Induce Antiviral Innate Immune Response through IFN-λ Regulation in Human Nasal Epithelial Cells

Kim

Kim²,

Ryu³

et al. 2013

Am J Respir Cell Mol Biol

116

117

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This study sought to explore the role of the IFN-related innate immune responses (IFN-b and IFN-l) and of reactive oxygen species (ROS) after influenza A virus (IAV) infection for antiviral innate immune activity in normal human nasal epithelial (NHNE) cells that are highly exposed to IAV. Passage-2 NHNE cells were inoculated with the IAV WSN/33 for 1, 2, and 3 days to assess the capacity of IFN and the relationship between ROS generation and IFN-l secretion for controlling IAV infection. Viral titers and IAV mRNA levels increased after infection. In concert with viral titers, we found that the generation of IFNs, such as IFN-b, IFN-l1, and IFN-l2/3, was induced after IAV infection until 3 days after infection. The induction of IFN-l gene expression and protein secretion may be predominant after IAV infection. Similarly, we observed that intracellular ROS generation increased 60 minutes after IAV infection. Viral titers and mRNA levels of IAV were significantly higher in cases with scavenging ROS, in cases with an induced IFN-l mRNA level, or where the secreted protein concentration of IFN-l was attenuated after the suppression of ROS generation. Both mitochondrial and dual oxidase (Doux)2-generated ROS were correlated with IAV mRNA and viral titers. The inhibition of mitochondrial ROS generation and the knockdown of Duox2 gene expression highly increased IAV viral titers and decreased IFN-l secretion. Our findings suggest that the production of ROS may be responsible for IFN-l secretion to control IAV infection. Both mitochondria and Duox2 are possible sources of ROS generation, which is required to initiate an innate immune response in NHNE cells.

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“…Interestingly, our data suggest that type I IFNs are not responsible for inducing such an antiviral state in RSV-infected WD-PBECs. Intriguingly, recent work suggests that type III IFNs may be implicated instead (33).…”

Section: Discussionmentioning

confidence: 99%

In vitro modeling of respiratory syncytial virus infection of pediatric bronchial epithelium, the primary target of infection in vivo

Villenave

Thavagnanam

Sarlang

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

166

214

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Respiratory syncytial virus (RSV) is the major viral cause of severe pulmonary disease in young infants worldwide. However, the mechanisms by which RSV causes disease in humans remain poorly understood. To help bridge this gap, we developed an ex vivo/in vitro model of RSV infection based on well-differentiated primary pediatric bronchial epithelial cells (WD-PBECs), the primary targets of RSV infection in vivo. Our RSV/WD-PBEC model demonstrated remarkable similarities to hallmarks of RSV infection in infant lungs. These hallmarks included restriction of infection to noncontiguous or small clumps of apical ciliated and occasional nonciliated epithelial cells, apoptosis and sloughing of apical epithelial cells, occasional syncytium formation, goblet cell hyperplasia/metaplasia, and mucus hypersecretion. RSV was shed exclusively from the apical surface at titers consistent with those in airway aspirates from hospitalized infants. Furthermore, secretion of proinflammatory chemokines such as CXCL10, CCL5, IL-6, and CXCL8 reflected those chemokines present in airway aspirates. Interestingly, a recent RSV clinical isolate induced more cytopathogenesis than the prototypic A2 strain. Our findings indicate that this RSV/WD-PBEC model provides an authentic surrogate for RSV infection of airway epithelium in vivo. As such, this model may provide insights into RSV pathogenesis in humans that ultimately lead to successful RSV vaccines or therapeutics.

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Type-III interferon, not type-I, is the predominant interferon induced by respiratory viruses in nasal epithelial cells

Cited by 129 publications

References 39 publications

Ciliary dyskinesia is an early feature of respiratory syncytial virus infection

Ciliary dyskinesia is an early feature of respiratory syncytial virus infection

Reactive Oxygen Species Induce Antiviral Innate Immune Response through IFN-λ Regulation in Human Nasal Epithelial Cells

In vitro modeling of respiratory syncytial virus infection of pediatric bronchial epithelium, the primary target of infection in vivo

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