SARS‑CoV‑2 spike protein‑induced host inflammatory response signature in human corneal epithelial cells

Area of Science:

• Ophthalmology
• Virology
• Immunology

Background:

• Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has led to a global pandemic.
• The ocular surface, including human corneal epithelial cells (HCECs), may be a potential site for SARS-CoV-2 infection.
• Understanding the host inflammatory response in HCECs is crucial for comprehending COVID-19 pathogenesis.

Purpose of the Study:

• To investigate the inflammatory response signature induced by SARS-CoV-2 in HCECs.
• To determine the expression of angiotensin-converting enzyme 2 (ACE2) in the human cornea and HCECs.
• To analyze the impact of SARS-CoV-2 spike protein on inflammatory markers and pyroptosis in HCECs.

Main Methods:

• Immunofluorescence was used to detect ACE2 expression in the cornea.
• In vitro experiments involved stimulating HCECs with SARS-CoV-2 spike protein.
• Reverse transcription-quantitative PCR and western blotting were employed to measure gene and protein expression levels of ACE2, IL-8, TNF-α, IL-6, GSDMD, and IL-1β.

Main Results:

• ACE2 expression was confirmed in normal human corneal epithelium and cultured HCECs.
• SARS-CoV-2 spike protein stimulation led to decreased expression of IL-8, TNF-α, and IL-6 in HCECs.
• Conversely, stimulation resulted in increased expression of GSDMD and IL-1β, indicating pyroptosis induction.

Conclusions:

• The SARS-CoV-2 spike protein suppresses the host inflammatory response in HCECs.
• SARS-CoV-2 spike protein induces pyroptosis in HCECs.
• Blocking the ACE2 receptor in HCECs could potentially reduce COVID-19 infection rates.