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

被引:0
|
作者
Gonzalez-Rubio, Julian [1 ]
Le-Trilling, Vu Thuy Khanh [2 ]
Baumann, Lea [1 ]
Cheremkhina, Maria [1 ]
Kubiza, Hannah [1 ]
Luengen, Anja E. [1 ,3 ]
Reuter, Sebastian [3 ]
Taube, Christian [3 ]
Ruetten, Stephan [4 ]
Campos, Daniela Duarte [5 ]
Cornelissen, Christian G. [1 ,6 ]
Trilling, Mirko [2 ]
Thiebes, Anja Lena [1 ]
机构
[1] RWTH Aachen Univ & Hosp, AME Inst Appl Med Engn, Helmholtz Inst, Dept Biohybrid & Med Text BioTex, Aachen, Germany
[2] Univ Duisburg Essen, Univ Hosp Essen, Inst Virol, Essen, Germany
[3] Univ Med Ctr Essen, Ruhrlandklin, Dept Pulm Med, Essen, Germany
[4] RWTH Aachen Univ Hosp, Inst Pathol Electron Microscopy Facil, Aachen, Germany
[5] Heidelberg Univ ZMBH, Bioprinting & Tissue Engn Grp, Ctr Mol Biol, Heidelberg, Germany
[6] RWTH Aachen Univ Hosp, Clin Pneumol & Internal Intens Care Med, Med Clin 5, Aachen, Germany
关键词
SARS-CoV-2; COVID-19; airway tissue engineering; lung innate immunity; epithelial cells; cilia; differentiation; stem cells; MOTILE CILIA; CELLS; REGENERATION; PATHOGENESIS; RESPONSES; BARRIER; HEALTH; REPAIR;
D O I
10.3389/fbioe.2023.1268782
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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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页数:12
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