Characterization of the SARS-CoV-2 Host Response in Primary Human Airway Epithelial Cells from Aged Individuals

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), a global pandemic characterized by an exaggerated immune response and respiratory illness. Age (>60 years) is a significant risk factor for developing severe COVID-19. To be...

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Main Authors: Bharathiraja Subramaniyan, Jason L. Larabee, Manish Bodas, Andrew R. Moore, Anthony W. G. Burgett, Dean A. Myers, Constantin Georgescu, Jonathan D. Wren, James F. Papin, Matthew S. Walters
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/13/8/1603
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spelling doaj-85d949504eb44c8f9251f1199d7ef4502021-08-26T14:27:04ZengMDPI AGViruses1999-49152021-08-01131603160310.3390/v13081603Characterization of the SARS-CoV-2 Host Response in Primary Human Airway Epithelial Cells from Aged IndividualsBharathiraja Subramaniyan0Jason L. Larabee1Manish Bodas2Andrew R. Moore3Anthony W. G. Burgett4Dean A. Myers5Constantin Georgescu6Jonathan D. Wren7James F. Papin8Matthew S. Walters9Department of Medicine, Section of Pulmonary, Critical Care & Sleep Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Medicine, Section of Pulmonary, Critical Care & Sleep Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Medicine, Section of Pulmonary, Critical Care & Sleep Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USAGenes & Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USAGenes & Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USADepartment of Pathology, Division of Comparative Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Medicine, Section of Pulmonary, Critical Care & Sleep Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USASevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), a global pandemic characterized by an exaggerated immune response and respiratory illness. Age (>60 years) is a significant risk factor for developing severe COVID-19. To better understand the host response of the aged airway epithelium to SARS-CoV-2 infection, we performed an in vitro study using primary human bronchial epithelial cells from donors >67 years of age differentiated on an air–liquid interface culture. We demonstrate that SARS-CoV-2 infection leads to early induction of a proinflammatory response and a delayed interferon response. In addition, we observed changes in the genes and pathways associated with cell death and senescence throughout infection. In summary, our study provides new and important insights into the temporal kinetics of the airway epithelial innate immune response to SARS-CoV-2 in older individuals.https://www.mdpi.com/1999-4915/13/8/1603COVID-19SARS-CoV-2air–liquid interfaceairway epitheliumimmune responseinnate immunity
collection DOAJ
language English
format Article
sources DOAJ
author Bharathiraja Subramaniyan
Jason L. Larabee
Manish Bodas
Andrew R. Moore
Anthony W. G. Burgett
Dean A. Myers
Constantin Georgescu
Jonathan D. Wren
James F. Papin
Matthew S. Walters
spellingShingle Bharathiraja Subramaniyan
Jason L. Larabee
Manish Bodas
Andrew R. Moore
Anthony W. G. Burgett
Dean A. Myers
Constantin Georgescu
Jonathan D. Wren
James F. Papin
Matthew S. Walters
Characterization of the SARS-CoV-2 Host Response in Primary Human Airway Epithelial Cells from Aged Individuals
Viruses
COVID-19
SARS-CoV-2
air–liquid interface
airway epithelium
immune response
innate immunity
author_facet Bharathiraja Subramaniyan
Jason L. Larabee
Manish Bodas
Andrew R. Moore
Anthony W. G. Burgett
Dean A. Myers
Constantin Georgescu
Jonathan D. Wren
James F. Papin
Matthew S. Walters
author_sort Bharathiraja Subramaniyan
title Characterization of the SARS-CoV-2 Host Response in Primary Human Airway Epithelial Cells from Aged Individuals
title_short Characterization of the SARS-CoV-2 Host Response in Primary Human Airway Epithelial Cells from Aged Individuals
title_full Characterization of the SARS-CoV-2 Host Response in Primary Human Airway Epithelial Cells from Aged Individuals
title_fullStr Characterization of the SARS-CoV-2 Host Response in Primary Human Airway Epithelial Cells from Aged Individuals
title_full_unstemmed Characterization of the SARS-CoV-2 Host Response in Primary Human Airway Epithelial Cells from Aged Individuals
title_sort characterization of the sars-cov-2 host response in primary human airway epithelial cells from aged individuals
publisher MDPI AG
series Viruses
issn 1999-4915
publishDate 2021-08-01
description Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), a global pandemic characterized by an exaggerated immune response and respiratory illness. Age (>60 years) is a significant risk factor for developing severe COVID-19. To better understand the host response of the aged airway epithelium to SARS-CoV-2 infection, we performed an in vitro study using primary human bronchial epithelial cells from donors >67 years of age differentiated on an air–liquid interface culture. We demonstrate that SARS-CoV-2 infection leads to early induction of a proinflammatory response and a delayed interferon response. In addition, we observed changes in the genes and pathways associated with cell death and senescence throughout infection. In summary, our study provides new and important insights into the temporal kinetics of the airway epithelial innate immune response to SARS-CoV-2 in older individuals.
topic COVID-19
SARS-CoV-2
air–liquid interface
airway epithelium
immune response
innate immunity
url https://www.mdpi.com/1999-4915/13/8/1603
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