Pyroptosis Mediated by ROS/Caspase-3/GSDME Pathway in Aspergillus fumigatus-Induced Fungal Keratitis

Area of Science:

• Ophthalmology
• Immunology
• Cell Biology

Background:

• Gasdermin E (GSDME) is a key pyroptosis executor.
• The role of GSDME in fungal keratitis (FK) is not well understood.

Purpose of the Study:

• To investigate the role of GSDME and its signaling pathway in Aspergillus fumigatus (AF)-induced FK.
• To analyze GSDME's involvement in pyroptosis and inflammation during AF infection.

Main Methods:

• Utilized a mouse model and human corneal epithelial cells for AF-induced FK.
• Assessed FK lesion progression, cytokine production, and pyroptosis markers via qRT-PCR, flow cytometry, TEM, and Western blotting.
• Investigated the effects of cytokine inhibitors on pyroptosis and inflammation.

Main Results:

• GSDME significantly mediated AF-induced pyroptosis in both mouse and human cell models.
• The reactive oxygen species (ROS)/casp-3/GSDME pathway was identified as crucial for AF-induced pyroptosis.
• GSDME influenced inflammatory processes and keratitis severity in AF-induced FK.

Conclusions:

• GSDME plays a critical role in pyroptosis and corneal inflammation during FK.
• GSDME modulates IL-1β release, impacting the host immune response in FK.
• Blocking the ROS/casp-3/GSDME pathway offers a potential therapeutic strategy for reducing corneal opacity in FK.