STING regulates NETs formation by activating GSDMD in influenza viral pneumonia

Area of Science:

• Immunology
• Virology
• Molecular Biology

Background:

• Viral pneumonia poses a significant global health threat, lacking broad-spectrum antiviral treatments.
• Understanding viral pneumonia pathogenesis is crucial for developing effective therapies.

Purpose of the Study:

• To investigate the role of STING (stimulator of interferon genes) in viral pneumonia progression.
• To identify potential therapeutic targets for viral pneumonia.

Main Methods:

• Viral pneumonia was induced in wild-type and STING knockout mice using the PR8 virus strain.
• Molecular biology techniques, including transcriptomic analysis and immunoprecipitation, were employed.
• The effects of a STING inhibitor (C-176) on pneumonia severity and cytokine levels were evaluated.

Main Results:

• STING activation in infected lungs amplified immune responses, worsening pneumonia symptoms.
• STING inhibition (C-176) significantly reduced lung inflammation and neutrophil extracellular traps (NETs) formation.
• STING-KO mice exhibited milder pneumonia and reduced NETs formation compared to wild-type mice.
• STING, gasdermin D (GSDMD), and NETs-related proteins were found to interact, with STING and GSDMD colocalizing on neutrophil membranes.

Conclusions:

• Targeted STING intervention alleviates viral pneumonia by inhibiting inflammation and NETs formation.
• Blocking STING inhibits GSDMD activation, thereby suppressing NETs formation and slowing pneumonia progression.