Rhinovirus Infection Drives Complex Host Airway Molecular Responses in Children With Cystic Fibrosis
Early-life viral infections are responsible for pulmonary exacerbations that can contribute to disease progression in young children with cystic fibrosis (CF). The most common respiratory viruses detected in the CF airway are human rhinoviruses (RV), and augmented airway inflammation in CF has been...
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Format: | Article |
Language: | English |
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Frontiers Media S.A.
2020-07-01
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Series: | Frontiers in Immunology |
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Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.01327/full |
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doaj-03987db3d864450e9a006f83bbab0eb4 |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kak-Ming Ling Kak-Ming Ling Kak-Ming Ling Luke W. Garratt Luke W. Garratt Luke W. Garratt Erin E. Gill Amy H. Y. Lee Patricia Agudelo-Romero Patricia Agudelo-Romero Erika N. Sutanto Erika N. Sutanto Thomas Iosifidis Thomas Iosifidis Tim Rosenow Tim Rosenow Stuart E. Turvey Timo Lassmann Robert E. W. Hancock Anthony Kicic Anthony Kicic Anthony Kicic Anthony Kicic Anthony Kicic Anthony Kicic Stephen M. Stick Stephen M. Stick Stephen M. Stick Stephen M. Stick Stephen M. Stick |
spellingShingle |
Kak-Ming Ling Kak-Ming Ling Kak-Ming Ling Luke W. Garratt Luke W. Garratt Luke W. Garratt Erin E. Gill Amy H. Y. Lee Patricia Agudelo-Romero Patricia Agudelo-Romero Erika N. Sutanto Erika N. Sutanto Thomas Iosifidis Thomas Iosifidis Tim Rosenow Tim Rosenow Stuart E. Turvey Timo Lassmann Robert E. W. Hancock Anthony Kicic Anthony Kicic Anthony Kicic Anthony Kicic Anthony Kicic Anthony Kicic Stephen M. Stick Stephen M. Stick Stephen M. Stick Stephen M. Stick Stephen M. Stick Rhinovirus Infection Drives Complex Host Airway Molecular Responses in Children With Cystic Fibrosis Frontiers in Immunology cystic fibrosis RV airway epithelial cells transcriptomic innate immune response |
author_facet |
Kak-Ming Ling Kak-Ming Ling Kak-Ming Ling Luke W. Garratt Luke W. Garratt Luke W. Garratt Erin E. Gill Amy H. Y. Lee Patricia Agudelo-Romero Patricia Agudelo-Romero Erika N. Sutanto Erika N. Sutanto Thomas Iosifidis Thomas Iosifidis Tim Rosenow Tim Rosenow Stuart E. Turvey Timo Lassmann Robert E. W. Hancock Anthony Kicic Anthony Kicic Anthony Kicic Anthony Kicic Anthony Kicic Anthony Kicic Stephen M. Stick Stephen M. Stick Stephen M. Stick Stephen M. Stick Stephen M. Stick |
author_sort |
Kak-Ming Ling |
title |
Rhinovirus Infection Drives Complex Host Airway Molecular Responses in Children With Cystic Fibrosis |
title_short |
Rhinovirus Infection Drives Complex Host Airway Molecular Responses in Children With Cystic Fibrosis |
title_full |
Rhinovirus Infection Drives Complex Host Airway Molecular Responses in Children With Cystic Fibrosis |
title_fullStr |
Rhinovirus Infection Drives Complex Host Airway Molecular Responses in Children With Cystic Fibrosis |
title_full_unstemmed |
Rhinovirus Infection Drives Complex Host Airway Molecular Responses in Children With Cystic Fibrosis |
title_sort |
rhinovirus infection drives complex host airway molecular responses in children with cystic fibrosis |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2020-07-01 |
description |
Early-life viral infections are responsible for pulmonary exacerbations that can contribute to disease progression in young children with cystic fibrosis (CF). The most common respiratory viruses detected in the CF airway are human rhinoviruses (RV), and augmented airway inflammation in CF has been attributed to dysregulated airway epithelial responses although evidence has been conflicting. Here, we exposed airway epithelial cells from children with and without CF to RV in vitro. Using RNA-Seq, we profiled the transcriptomic differences of CF and non-CF airway epithelial cells at baseline and in response to RV. There were only modest differences between CF and non-CF cells at baseline. In response to RV, there were 1,442 and 896 differentially expressed genes in CF and non-CF airway epithelial cells, respectively. The core antiviral responses in CF and non-CF airway epithelial cells were mediated through interferon signaling although type 1 and 3 interferon signaling, when measured, were reduced in CF airway epithelial cells following viral challenge consistent with previous reports. The transcriptional responses in CF airway epithelial cells were more complex than in non-CF airway epithelial cells with diverse over-represented biological pathways, such as cytokine signaling and metabolic and biosynthetic pathways. Network analysis highlighted that the differentially expressed genes of CF airway epithelial cells' transcriptional responses were highly interconnected and formed a more complex network than observed in non-CF airway epithelial cells. We corroborate observations in fully differentiated air–liquid interface (ALI) cultures, identifying genes involved in IL-1 signaling and mucin glycosylation that are only dysregulated in the CF airway epithelial response to RV infection. These data provide novel insights into the CF airway epithelial cells' responses to RV infection and highlight potential pathways that could be targeted to improve antiviral and anti-inflammatory responses in CF. |
topic |
cystic fibrosis RV airway epithelial cells transcriptomic innate immune response |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2020.01327/full |
work_keys_str_mv |
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doaj-03987db3d864450e9a006f83bbab0eb42020-11-25T03:28:13ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-07-011110.3389/fimmu.2020.01327500893Rhinovirus Infection Drives Complex Host Airway Molecular Responses in Children With Cystic FibrosisKak-Ming Ling0Kak-Ming Ling1Kak-Ming Ling2Luke W. Garratt3Luke W. Garratt4Luke W. Garratt5Erin E. Gill6Amy H. Y. Lee7Patricia Agudelo-Romero8Patricia Agudelo-Romero9Erika N. Sutanto10Erika N. Sutanto11Thomas Iosifidis12Thomas Iosifidis13Tim Rosenow14Tim Rosenow15Stuart E. Turvey16Timo Lassmann17Robert E. W. Hancock18Anthony Kicic19Anthony Kicic20Anthony Kicic21Anthony Kicic22Anthony Kicic23Anthony Kicic24Stephen M. Stick25Stephen M. Stick26Stephen M. Stick27Stephen M. Stick28Stephen M. Stick29Paediatrics, Medical School, Faculty of Healthy and Medical Science, The University of Western Australia, Nedlands, WA, AustraliaTelethon Kids Institute, Respiratory Research Centre, Nedlands, WA, AustraliaTelethon Kids Institute, Centre for Health Research, The University of Western Australia, Nedlands, WA, AustraliaTelethon Kids Institute, Respiratory Research Centre, Nedlands, WA, AustraliaTelethon Kids Institute, Centre for Health Research, The University of Western Australia, Nedlands, WA, AustraliaSchool of Biomedical Sciences, The University of Western Australia, Nedlands, WA, AustraliaCentre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, BC, CanadaCentre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, BC, CanadaTelethon Kids Institute, Respiratory Research Centre, Nedlands, WA, AustraliaTelethon Kids Institute, Centre for Health Research, The University of Western Australia, Nedlands, WA, AustraliaTelethon Kids Institute, Respiratory Research Centre, Nedlands, WA, AustraliaTelethon Kids Institute, Centre for Health Research, The University of Western Australia, Nedlands, WA, AustraliaTelethon Kids Institute, Respiratory Research Centre, Nedlands, WA, AustraliaTelethon Kids Institute, Centre for Health Research, The University of Western Australia, Nedlands, WA, AustraliaTelethon Kids Institute, Respiratory Research Centre, Nedlands, WA, AustraliaTelethon Kids Institute, Centre for Health Research, The University of Western Australia, Nedlands, WA, AustraliaDepartment of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, BC, CanadaTelethon Kids Institute, Centre for Health Research, The University of Western Australia, Nedlands, WA, AustraliaCentre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, BC, CanadaTelethon Kids Institute, Respiratory Research Centre, Nedlands, WA, AustraliaTelethon Kids Institute, Centre for Health Research, The University of Western Australia, Nedlands, WA, AustraliaSchool of Biomedical Sciences, The University of Western Australia, Nedlands, WA, AustraliaOccupation and Environment, School of Public Health, Curtin University, Perth, WA, AustraliaDepartment of Respiratory and Sleep Medicine, Perth Children's Hospital, Nedlands, WA, AustraliaCentre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, The University of Western Australia, Nedlands, WA, AustraliaTelethon Kids Institute, Respiratory Research Centre, Nedlands, WA, AustraliaTelethon Kids Institute, Centre for Health Research, The University of Western Australia, Nedlands, WA, AustraliaSchool of Biomedical Sciences, The University of Western Australia, Nedlands, WA, AustraliaDepartment of Respiratory and Sleep Medicine, Perth Children's Hospital, Nedlands, WA, AustraliaCentre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, The University of Western Australia, Nedlands, WA, AustraliaEarly-life viral infections are responsible for pulmonary exacerbations that can contribute to disease progression in young children with cystic fibrosis (CF). The most common respiratory viruses detected in the CF airway are human rhinoviruses (RV), and augmented airway inflammation in CF has been attributed to dysregulated airway epithelial responses although evidence has been conflicting. Here, we exposed airway epithelial cells from children with and without CF to RV in vitro. Using RNA-Seq, we profiled the transcriptomic differences of CF and non-CF airway epithelial cells at baseline and in response to RV. There were only modest differences between CF and non-CF cells at baseline. In response to RV, there were 1,442 and 896 differentially expressed genes in CF and non-CF airway epithelial cells, respectively. The core antiviral responses in CF and non-CF airway epithelial cells were mediated through interferon signaling although type 1 and 3 interferon signaling, when measured, were reduced in CF airway epithelial cells following viral challenge consistent with previous reports. The transcriptional responses in CF airway epithelial cells were more complex than in non-CF airway epithelial cells with diverse over-represented biological pathways, such as cytokine signaling and metabolic and biosynthetic pathways. Network analysis highlighted that the differentially expressed genes of CF airway epithelial cells' transcriptional responses were highly interconnected and formed a more complex network than observed in non-CF airway epithelial cells. We corroborate observations in fully differentiated air–liquid interface (ALI) cultures, identifying genes involved in IL-1 signaling and mucin glycosylation that are only dysregulated in the CF airway epithelial response to RV infection. These data provide novel insights into the CF airway epithelial cells' responses to RV infection and highlight potential pathways that could be targeted to improve antiviral and anti-inflammatory responses in CF.https://www.frontiersin.org/article/10.3389/fimmu.2020.01327/fullcystic fibrosisRVairway epithelial cellstranscriptomicinnate immune response |