SARS-CoV-2 particles promote airway epithelial differentiation and ciliation

Introduction: The Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which caused the coronavirus disease 2019 (COVID-19) pandemic, enters the human body via the epithelial cells of the airway tract. To trap and eject pathogens, the airway epithelium is composed of ciliated and secre...

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Những tác giả chính: Julian Gonzalez-Rubio, Vu Thuy Khanh Le-Trilling, Lea Baumann, Maria Cheremkhina, Hannah Kubiza, Anja E. Luengen, Sebastian Reuter, Christian Taube, Stephan Ruetten, Daniela Duarte Campos, Christian G. Cornelissen, Mirko Trilling, Anja Lena Thiebes
Định dạng: Bài viết
Ngôn ngữ:English
Được phát hành: Frontiers Media S.A. 2023-11-01
Loạt:Frontiers in Bioengineering and Biotechnology
Những chủ đề:
Truy cập trực tuyến:https://www.frontiersin.org/articles/10.3389/fbioe.2023.1268782/full
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author Julian Gonzalez-Rubio
Vu Thuy Khanh Le-Trilling
Lea Baumann
Maria Cheremkhina
Hannah Kubiza
Anja E. Luengen
Anja E. Luengen
Sebastian Reuter
Christian Taube
Stephan Ruetten
Daniela Duarte Campos
Christian G. Cornelissen
Christian G. Cornelissen
Mirko Trilling
Anja Lena Thiebes
author_facet Julian Gonzalez-Rubio
Vu Thuy Khanh Le-Trilling
Lea Baumann
Maria Cheremkhina
Hannah Kubiza
Anja E. Luengen
Anja E. Luengen
Sebastian Reuter
Christian Taube
Stephan Ruetten
Daniela Duarte Campos
Christian G. Cornelissen
Christian G. Cornelissen
Mirko Trilling
Anja Lena Thiebes
author_sort Julian Gonzalez-Rubio
collection DOAJ
description Introduction: The Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which caused the coronavirus disease 2019 (COVID-19) pandemic, enters the human body via the epithelial cells of the airway tract. To trap and eject pathogens, the airway epithelium is composed of ciliated and secretory cells that produce mucus which is expelled through a process called mucociliary clearance.Methods: This study examines the early stages of contact between SARS-CoV-2 particles and the respiratory epithelium, utilizing 3D airway tri-culture models exposed to ultraviolet light-irradiated virus particles. These cultures are composed of human endothelial cells and human tracheal mesenchymal cells in a fibrin hydrogel matrix covered by mucociliated human tracheal epithelial cells.Results: We found that SARS-CoV-2 particles trigger a significant increase in ciliation on the epithelial surface instructed through a differentiation of club cells and basal stem cells. The contact with SARS-CoV-2 particles also provoked a loss of cell-cell tight junctions and impaired the barrier integrity. Further immunofluorescence analyses revealed an increase in FOXJ1 expression and PAK1/2 phosphorylation associated with particle-induced ciliation.Discussion: An understanding of epithelial responses to virus particles may be instrumental to prevent or treat respiratory infectious diseases such as COVID-19.
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spelling doaj.art-f28e7f99ee7b4a2abc7feccf177ffcb32023-11-03T06:14:53ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852023-11-011110.3389/fbioe.2023.12687821268782SARS-CoV-2 particles promote airway epithelial differentiation and ciliationJulian Gonzalez-Rubio0Vu Thuy Khanh Le-Trilling1Lea Baumann2Maria Cheremkhina3Hannah Kubiza4Anja E. Luengen5Anja E. Luengen6Sebastian Reuter7Christian Taube8Stephan Ruetten9Daniela Duarte Campos10Christian G. Cornelissen11Christian G. Cornelissen12Mirko Trilling13Anja Lena Thiebes14Department of Biohybrid and Medical Textiles (BioTex), AME—Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University, Aachen, GermanyInstitute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyDepartment of Biohybrid and Medical Textiles (BioTex), AME—Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University, Aachen, GermanyDepartment of Biohybrid and Medical Textiles (BioTex), AME—Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University, Aachen, GermanyDepartment of Biohybrid and Medical Textiles (BioTex), AME—Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University, Aachen, GermanyDepartment of Biohybrid and Medical Textiles (BioTex), AME—Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University, Aachen, GermanyDepartment of Pulmonary Medicine, University Medical Center Essen—Ruhrlandklinik, Essen, GermanyDepartment of Pulmonary Medicine, University Medical Center Essen—Ruhrlandklinik, Essen, GermanyDepartment of Pulmonary Medicine, University Medical Center Essen—Ruhrlandklinik, Essen, GermanyInstitute of Pathology, Electron Microscopy Facility, RWTH Aachen University Hospital, Aachen, GermanyBioprinting and Tissue Engineering Group, Center for Molecular Biology of Heidelberg University (ZMBH), Heidelberg, GermanyDepartment of Biohybrid and Medical Textiles (BioTex), AME—Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University, Aachen, GermanyClinic for Pneumology and Internal Intensive Care Medicine (Medical Clinic V), RWTH Aachen University Hospital, Aachen, GermanyInstitute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyDepartment of Biohybrid and Medical Textiles (BioTex), AME—Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University, Aachen, GermanyIntroduction: The Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which caused the coronavirus disease 2019 (COVID-19) pandemic, enters the human body via the epithelial cells of the airway tract. To trap and eject pathogens, the airway epithelium is composed of ciliated and secretory cells that produce mucus which is expelled through a process called mucociliary clearance.Methods: This study examines the early stages of contact between SARS-CoV-2 particles and the respiratory epithelium, utilizing 3D airway tri-culture models exposed to ultraviolet light-irradiated virus particles. These cultures are composed of human endothelial cells and human tracheal mesenchymal cells in a fibrin hydrogel matrix covered by mucociliated human tracheal epithelial cells.Results: We found that SARS-CoV-2 particles trigger a significant increase in ciliation on the epithelial surface instructed through a differentiation of club cells and basal stem cells. The contact with SARS-CoV-2 particles also provoked a loss of cell-cell tight junctions and impaired the barrier integrity. Further immunofluorescence analyses revealed an increase in FOXJ1 expression and PAK1/2 phosphorylation associated with particle-induced ciliation.Discussion: An understanding of epithelial responses to virus particles may be instrumental to prevent or treat respiratory infectious diseases such as COVID-19.https://www.frontiersin.org/articles/10.3389/fbioe.2023.1268782/fullSARS-CoV-2COVID-19airway tissue engineeringlung innate immunityepithelial cellscilia
spellingShingle Julian Gonzalez-Rubio
Vu Thuy Khanh Le-Trilling
Lea Baumann
Maria Cheremkhina
Hannah Kubiza
Anja E. Luengen
Anja E. Luengen
Sebastian Reuter
Christian Taube
Stephan Ruetten
Daniela Duarte Campos
Christian G. Cornelissen
Christian G. Cornelissen
Mirko Trilling
Anja Lena Thiebes
SARS-CoV-2 particles promote airway epithelial differentiation and ciliation
Frontiers in Bioengineering and Biotechnology
SARS-CoV-2
COVID-19
airway tissue engineering
lung innate immunity
epithelial cells
cilia
title SARS-CoV-2 particles promote airway epithelial differentiation and ciliation
title_full SARS-CoV-2 particles promote airway epithelial differentiation and ciliation
title_fullStr SARS-CoV-2 particles promote airway epithelial differentiation and ciliation
title_full_unstemmed SARS-CoV-2 particles promote airway epithelial differentiation and ciliation
title_short SARS-CoV-2 particles promote airway epithelial differentiation and ciliation
title_sort sars cov 2 particles promote airway epithelial differentiation and ciliation
topic SARS-CoV-2
COVID-19
airway tissue engineering
lung innate immunity
epithelial cells
cilia
url https://www.frontiersin.org/articles/10.3389/fbioe.2023.1268782/full
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