SARS-CoV-2 infection of human-induced pluripotent stem cells-derived lung lineage cells evokes inflammatory and chemosensory responses by targeting mitochondrial pathways.

SARS-CoV-2 chemosensory response induced pluripotent stem cells inflammatory response lung epithelial cells mitochondrial damage

Journal

Journal of cellular physiology
ISSN: 1097-4652
Titre abrégé: J Cell Physiol
Pays: United States
ID NLM: 0050222

Informations de publication

Date de publication:
07 2022
Historique:
revised: 07 03 2022
received: 22 01 2022
accepted: 29 03 2022
pubmed: 24 4 2022
medline: 16 7 2022
entrez: 23 4 2022
Statut: ppublish

Résumé

The COVID-19 disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily affects the lung, particularly the proximal airway and distal alveolar cells. NKX2.1+ primordial lung progenitors of the foregut (anterior) endoderm are the developmental precursors to all adult lung epithelial lineages and are postulated to play an important role in viral tropism. Here, we show that SARS-CoV-2 readily infected and replicated in human-induced pluripotent stem cell-derived proximal airway cells, distal alveolar cells, and lung progenitors. In addition to the upregulation of antiviral defense and immune responses, transcriptomics data uncovered a robust epithelial cell-specific response, including perturbation of metabolic processes and disruption in the alveolar maturation program. We also identified spatiotemporal dysregulation of mitochondrial heme oxygenase 1 (HMOX1), which is associated with defense against antioxidant-induced lung injury. Cytokines, such as TNF-α, INF-γ, IL-6, and IL-13, were upregulated in infected cells sparking mitochondrial ROS production and change in electron transport chain complexes. Increased mitochondrial ROS then activated additional proinflammatory cytokines leading to an aberrant cell cycle resulting in apoptosis. Notably, we are the first to report a chemosensory response resulting from SARS-CoV-2 infection similar to that seen in COVID-19 patients. Some of our key findings were validated using COVID-19-affected postmortem lung tissue sections. These results suggest that our in vitro system could serve as a suitable model to investigate the pathogenetic mechanisms of SARS-CoV-2 infection and to discover and test therapeutic drugs against COVID-19 or its consequences.

Identifiants

pubmed: 35460571
doi: 10.1002/jcp.30755
pmc: PMC9088312
doi:

Substances chimiques

Cytokines 0
Reactive Oxygen Species 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2913-2928

Subventions

Organisme : COVID-19 Research Consortium, Department of Biotechnology (DBT) and Biotechnology Industry Research Assistance Council (BIRAC), Government of India
ID : BT/COVID0046/01/20

Informations de copyright

© 2022 Wiley Periodicals LLC.

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Auteurs

Harshini Surendran (H)

Eyestem Research, Centre for Cellular and Molecular Platforms (C-CAMP), Bengaluru, Karnataka, India.

Saurabh Kumar (S)

Clinical and Cellular Virology Laboratory, Translational Health Science and Technology Institute (THSTI), Faridabad, Haryana, India.

Swathi Narasimhaiah (S)

Eyestem Research, Centre for Cellular and Molecular Platforms (C-CAMP), Bengaluru, Karnataka, India.

Anuradha Ananthamurthy (A)

St John's Medical College, Bengaluru, Karnataka, India.

P S Varghese (PS)

St John's Medical College, Bengaluru, Karnataka, India.

George A D'Souza (GA)

St John's Medical College, Bengaluru, Karnataka, India.

Guruprasad Medigeshi (G)

Clinical and Cellular Virology Laboratory, Translational Health Science and Technology Institute (THSTI), Faridabad, Haryana, India.

Rajarshi Pal (R)

Eyestem Research, Centre for Cellular and Molecular Platforms (C-CAMP), Bengaluru, Karnataka, India.
The University of Trans-disciplinary Health Sciences and Technology (TDU), Bengaluru, Karnataka, India.

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