SARS-CoV-2 infection impairs NK cell functions

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Natural killer (NK) cells are crucial for controlling viral infections.
• COVID-19 is associated with immune dysregulation, including impaired NK cell function.
• The precise mechanisms of NK cell inhibition during SARS-CoV-2 infection are not fully understood.

Purpose of the Study:

• To investigate how SARS-CoV-2 infection affects NK cell phenotype and function.
• To elucidate the interplay between SARS-CoV-2 infected cells and NK cells.
• To identify novel mechanisms of NK cell inhibition in COVID-19.

Main Methods:

• Co-culture of NK cells with SARS-CoV-2 infected airway epithelial cells (A549ACE2/TMPRSS2 cell line and 3D ex vivo human airway epithelium model).
• Analysis of NK cell surface receptor expression (including CD161).
• Detection of lectin-like transcript 1 (LLT1) in cell supernatants, HAE basolateral medium, and patient serum.
• Treatment of NK cells with soluble LLT1 protein.

Main Results:

• SARS-CoV-2 infection selectively downregulated CD161 expression on NK cells, impairing their cytotoxicity.
• SARS-CoV-2 infection upregulated LLT1 ligand on infected epithelial cells.
• LLT1 was detected in patient serum.
• Soluble LLT1 protein reduced CD161+ NK cells, NK cell antiviral activity, and granzyme B production.

Conclusions:

• A novel mechanism of SARS-CoV-2-mediated NK cell inhibition involves the LLT1-CD161 axis.
• This pathway contributes to immune dysregulation observed in COVID-19 patients.
• Targeting the LLT1-CD161 axis may offer therapeutic potential.