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SARS-CoV-2 Infection of Pluripotent Stem Cell-Derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response
A hallmark of severe COVID-19 pneumonia is SARS-CoV-2 infection of the facultative progenitors of lung alveoli, the alveolar epithelial type 2 cells (AT2s). However, inability to access these cells from patients, particularly at early stages of disease, limits an understanding of disease inception....
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500949/ https://www.ncbi.nlm.nih.gov/pubmed/32979316 http://dx.doi.org/10.1016/j.stem.2020.09.013 |
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author | Huang, Jessie Hume, Adam J. Abo, Kristine M. Werder, Rhiannon B. Villacorta-Martin, Carlos Alysandratos, Konstantinos-Dionysios Beermann, Mary Lou Simone-Roach, Chantelle Lindstrom-Vautrin, Jonathan Olejnik, Judith Suder, Ellen L. Bullitt, Esther Hinds, Anne Sharma, Arjun Bosmann, Markus Wang, Ruobing Hawkins, Finn Burks, Eric J. Saeed, Mohsan Wilson, Andrew A. Mühlberger, Elke Kotton, Darrell N. |
author_facet | Huang, Jessie Hume, Adam J. Abo, Kristine M. Werder, Rhiannon B. Villacorta-Martin, Carlos Alysandratos, Konstantinos-Dionysios Beermann, Mary Lou Simone-Roach, Chantelle Lindstrom-Vautrin, Jonathan Olejnik, Judith Suder, Ellen L. Bullitt, Esther Hinds, Anne Sharma, Arjun Bosmann, Markus Wang, Ruobing Hawkins, Finn Burks, Eric J. Saeed, Mohsan Wilson, Andrew A. Mühlberger, Elke Kotton, Darrell N. |
author_sort | Huang, Jessie |
collection | PubMed |
description | A hallmark of severe COVID-19 pneumonia is SARS-CoV-2 infection of the facultative progenitors of lung alveoli, the alveolar epithelial type 2 cells (AT2s). However, inability to access these cells from patients, particularly at early stages of disease, limits an understanding of disease inception. Here, we present an in vitro human model that simulates the initial apical infection of alveolar epithelium with SARS-CoV-2 by using induced pluripotent stem cell-derived AT2s that have been adapted to air-liquid interface culture. We find a rapid transcriptomic change in infected cells, characterized by a shift to an inflammatory phenotype with upregulation of NF-κB signaling and loss of the mature alveolar program. Drug testing confirms the efficacy of remdesivir as well as TMPRSS2 protease inhibition, validating a putative mechanism used for viral entry in alveolar cells. Our model system reveals cell-intrinsic responses of a key lung target cell to SARS-CoV-2 infection and should facilitate drug development. |
format | Online Article Text |
id | pubmed-7500949 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-75009492020-09-21 SARS-CoV-2 Infection of Pluripotent Stem Cell-Derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response Huang, Jessie Hume, Adam J. Abo, Kristine M. Werder, Rhiannon B. Villacorta-Martin, Carlos Alysandratos, Konstantinos-Dionysios Beermann, Mary Lou Simone-Roach, Chantelle Lindstrom-Vautrin, Jonathan Olejnik, Judith Suder, Ellen L. Bullitt, Esther Hinds, Anne Sharma, Arjun Bosmann, Markus Wang, Ruobing Hawkins, Finn Burks, Eric J. Saeed, Mohsan Wilson, Andrew A. Mühlberger, Elke Kotton, Darrell N. Cell Stem Cell Resource A hallmark of severe COVID-19 pneumonia is SARS-CoV-2 infection of the facultative progenitors of lung alveoli, the alveolar epithelial type 2 cells (AT2s). However, inability to access these cells from patients, particularly at early stages of disease, limits an understanding of disease inception. Here, we present an in vitro human model that simulates the initial apical infection of alveolar epithelium with SARS-CoV-2 by using induced pluripotent stem cell-derived AT2s that have been adapted to air-liquid interface culture. We find a rapid transcriptomic change in infected cells, characterized by a shift to an inflammatory phenotype with upregulation of NF-κB signaling and loss of the mature alveolar program. Drug testing confirms the efficacy of remdesivir as well as TMPRSS2 protease inhibition, validating a putative mechanism used for viral entry in alveolar cells. Our model system reveals cell-intrinsic responses of a key lung target cell to SARS-CoV-2 infection and should facilitate drug development. Elsevier Inc. 2020-12-03 2020-09-18 /pmc/articles/PMC7500949/ /pubmed/32979316 http://dx.doi.org/10.1016/j.stem.2020.09.013 Text en © 2020 Elsevier Inc. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Resource Huang, Jessie Hume, Adam J. Abo, Kristine M. Werder, Rhiannon B. Villacorta-Martin, Carlos Alysandratos, Konstantinos-Dionysios Beermann, Mary Lou Simone-Roach, Chantelle Lindstrom-Vautrin, Jonathan Olejnik, Judith Suder, Ellen L. Bullitt, Esther Hinds, Anne Sharma, Arjun Bosmann, Markus Wang, Ruobing Hawkins, Finn Burks, Eric J. Saeed, Mohsan Wilson, Andrew A. Mühlberger, Elke Kotton, Darrell N. SARS-CoV-2 Infection of Pluripotent Stem Cell-Derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response |
title | SARS-CoV-2 Infection of Pluripotent Stem Cell-Derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response |
title_full | SARS-CoV-2 Infection of Pluripotent Stem Cell-Derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response |
title_fullStr | SARS-CoV-2 Infection of Pluripotent Stem Cell-Derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response |
title_full_unstemmed | SARS-CoV-2 Infection of Pluripotent Stem Cell-Derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response |
title_short | SARS-CoV-2 Infection of Pluripotent Stem Cell-Derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response |
title_sort | sars-cov-2 infection of pluripotent stem cell-derived human lung alveolar type 2 cells elicits a rapid epithelial-intrinsic inflammatory response |
topic | Resource |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500949/ https://www.ncbi.nlm.nih.gov/pubmed/32979316 http://dx.doi.org/10.1016/j.stem.2020.09.013 |
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