Type III interferons disrupt the lung epithelial barrier upon viral recognition

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.