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Updated: Nov 27, 2025
Multicellular Human Alveolar Model Composed of Epithelial Cells and Primary Immune Cells for Hazard Assessment
Published on: May 6, 2020
An organoid-derived bronchioalveolar model for SARS-CoV-2 infection of human alveolar type II-like cells
Mart M Lamers1, Jelte van der Vaart2, Kèvin Knoops3
1Viroscience Department, Erasmus University Medical Center, Rotterdam, The Netherlands.
Abstract:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which may result in acute respiratory distress syndrome (ARDS), multiorgan failure, and death. The alveolar epithelium is a major target of the virus, but representative models to study virus host interactions in more detail are currently lacking. Here, we describe a human 2D air-liquid interface culture system which was characterized by confocal and electron microscopy and single-cell mRNA expression analysis. In this model, alveolar cells, but also basal cells and rare neuroendocrine cells, are grown from 3D self-renewing fetal lung bud tip organoids. These cultures were readily infected by SARS-CoV-2 with mainly surfactant protein C-positive alveolar type II-like cells being targeted. Consequently, significant viral titers were detected and mRNA expression analysis revealed induction of type I/III interferon response program. Treatment of these cultures with a low dose of interferon lambda 1 reduced viral replication. Hence, these cultures represent an experimental model for SARS-CoV-2 infection and can be applied for drug screens.
Insights
Researchers developed a human 2D air-liquid interface culture model to study severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This model successfully mimics host-virus interactions and can be used for drug screening against COVID-19.
Area of Science:
- Pulmonology
- Virology
- Cell Biology
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, leading to severe respiratory distress and potential fatality.
- The alveolar epithelium is a primary target for SARS-CoV-2, but suitable models for studying these interactions are limited.
Purpose of the Study:
- To establish and characterize a novel human 2D air-liquid interface (ALI) culture system for modeling SARS-CoV-2 infection.
- To investigate the cellular targets and host responses within this ALI model upon SARS-CoV-2 infection.
- To evaluate the potential of this model for antiviral drug screening.
Main Methods:
- Development of a 2D ALI culture system using cells derived from 3D fetal lung bud tip organoids.
- Characterization of the ALI model using confocal microscopy, electron microscopy, and single-cell mRNA expression analysis.
- Infection of the ALI model with SARS-CoV-2 and assessment of viral replication and host response.
Main Results:
- The ALI cultures comprised alveolar cells, basal cells, and neuroendocrine cells, mimicking human lung tissue.
- SARS-CoV-2 readily infected surfactant protein C-positive alveolar type II-like cells, leading to significant viral titers.
- Infection induced a type I/III interferon response, and treatment with interferon lambda 1 reduced viral replication.
Conclusions:
- The developed human 2D ALI culture system serves as a representative experimental model for SARS-CoV-2 infection.
- This model allows detailed study of virus-host interactions in the alveolar epithelium.
- The system is suitable for high-throughput drug screening to identify potential COVID-19 therapeutics.
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