Cxcl10 is protective during mouse-adapted SARS-CoV-2 infection

Area of Science:

• Immunology
• Virology
• Pathogenesis of infectious diseases

Background:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the ongoing COVID-19 pandemic.
• Elevated chemokine CXCL10 levels correlate with poor COVID-19 outcomes, but its specific role and therapeutic potential remain unclear.

Purpose of the Study:

• To investigate the role of CXCL10 in SARS-CoV-2 pathogenesis using a mouse model.
• To determine if CXCL10 is a suitable therapeutic target for severe COVID-19.

Main Methods:

• Mice genetically deficient in Cxcl10 (Cxcl10-/-) were infected with a mouse-adapted SARS-CoV-2 strain.
• Mortality, lung histopathology, inflammatory gene expression, viral load, and immune cell infiltration were assessed.

Main Results:

• Male Cxcl10-/- mice exhibited increased mortality compared to wild-type controls.
• Lung pathology, inflammation, and viral load were not significantly altered by Cxcl10 deficiency in male mice.
• Absence of CXCL10 reduced B and T lymphocyte accumulation in the lungs of infected mice.

Conclusions:

• CXCL10 plays a role in regulating lymphocyte infiltration in the lungs during acute SARS-CoV-2 infection.
• CXCL10 confers protection against mortality in a male mouse model of SARS-CoV-2 infection.
• These preclinical findings do not support targeting CXCL10 therapeutically for severe COVID-19.