Lambda Interferon Restructures the Nasal Microbiome and Increases Susceptibility to Staphylococcus aureus...

Area of Science:

• Immunology
• Microbiology
• Virology

Background:

• Influenza virus and Staphylococcus aureus (S. aureus) coinfections cause significant respiratory illness.
• The role of the type III interferon pathway in mediating susceptibility to S. aureus superinfection following influenza is not fully understood.

Purpose of the Study:

• To investigate how influenza virus infection impacts the upper airway microbiome.
• To determine the role of type III interferons in mediating susceptibility to S. aureus coinfection after influenza virus infection.

Main Methods:

• Utilized wild-type (WT) and Il28r(-/-) mutant mice lacking the type III interferon receptor.
• Analyzed changes in the upper respiratory microbiota composition and host immune responses (STAT1 phosphorylation, IL-22, Ngal, RegIIIγ).
• Conducted coinfection studies with methicillin-resistant S. aureus (MRSA) following influenza virus infection.

Main Results:

• Influenza virus infection induced significant changes in the upper respiratory microbiota in WT mice, but not in Il28r(-/-) mice.
• Il28r(-/-) mice exhibited altered STAT1 and IL-22 signaling pathways.
• WT mice showed increased susceptibility to MRSA colonization and pneumonia compared to Il28r(-/-) mice after influenza infection.

Conclusions:

• Type III interferon signaling, induced by influenza virus, plays a critical role in restructuring the upper airway microbiome.
• This restructuring increases susceptibility to secondary bacterial infections, such as MRSA pneumonia.
• Targeting type III interferon pathways could be a strategy to prevent severe outcomes of influenza-bacterial coinfections.