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Updated: Dec 18, 2025
High-throughput Quantitative Real-time RT-PCR Assay for Determining Expression Profiles of Types I and III Interferon Subtypes
Published on: March 24, 2015
Type III interferons disrupt the lung epithelial barrier upon viral recognition
Achille Broggi1, Sreya Ghosh1, Benedetta Sposito1,2
1Harvard Medical School, Boston Children's Hospital, Division of Immunology, Boston, MA, USA.
Abstract:
Viral infections of the lower respiratory tract are a leading cause of mortality. Mounting evidence indicates that most severe cases are characterized by aberrant immune responses and do not depend on viral burden. In this study, we assessed how type III interferons (IFN-λ) contribute to the pathogenesis induced by RNA viruses. We report that IFN-λ is present in the lower, but not upper, airways of patients with coronavirus disease 2019 (COVID-19). In mice, we demonstrate that IFN-λ produced by lung dendritic cells in response to a synthetic viral RNA induces barrier damage, causing susceptibility to lethal bacterial superinfections. These findings provide a strong rationale for rethinking the pathophysiological role of IFN-λ and its possible use in clinical practice against endemic viruses, such as influenza virus as well as the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
Insights
Type III interferons (IFN-λ) cause lung damage and increase susceptibility to bacterial infections during viral respiratory illnesses like COVID-19. This suggests new therapeutic strategies targeting IFN-λ.
Area of Science:
- Immunology
- Virology
- Respiratory Medicine
Background:
- Lower respiratory tract viral infections cause significant mortality.
- Severe cases often involve immune dysregulation rather than high viral load.
- Type III interferons (IFN-λ) are key antiviral proteins, but their role in severe disease is unclear.
Purpose of the Study:
- To investigate the role of type III interferons (IFN-λ) in the pathogenesis of RNA virus-induced respiratory infections.
- To determine the clinical relevance of IFN-λ in coronavirus disease 2019 (COVID-19) and other viral respiratory diseases.
Main Methods:
- Analysis of IFN-λ levels in the airways of COVID-19 patients.
- In vivo studies using a mouse model with synthetic viral RNA to assess IFN-λ function.
- Evaluation of lung barrier integrity and susceptibility to secondary bacterial infections in mice.
Main Results:
- IFN-λ was detected in the lower airways but not the upper airways of COVID-19 patients.
- In mice, IFN-λ induced by lung dendritic cells led to lung barrier damage.
- This damage increased susceptibility to lethal bacterial superinfections.
Conclusions:
- IFN-λ contributes to lung pathology and secondary bacterial infections during viral respiratory infections.
- These findings challenge the protective role of IFN-λ in severe disease and suggest it may be a therapeutic target.
- Targeting IFN-λ could be beneficial for treating infections caused by viruses like influenza and SARS-CoV-2.
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