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

Shamik Majumdar1, Joseph D Weaver1, Sergio M Pontejo1

  • 1Molecular Signaling Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, United States.

Journal of Leukocyte Biology
|November 28, 2024
PubMed
Summary

Chemokine CXCL10 regulates lymphocyte infiltration in the lungs during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, targeting CXCL10 is not recommended for treating severe coronavirus disease 2019 (COVID-19).

Keywords:
COVID-19chemokinechemokine receptorcytokinelymphocytes

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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.