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Natural Killer Cells Do Not Attenuate a Mouse-Adapted SARS-CoV-2-Induced Disease in Rag2-/- Mice

Calder R Ellsworth1,2, Chenxiao Wang1,2, Alexis R Katz3

  • 1Division of Comparative Pathology, Tulane National Primate Research Center, Health Sciences Campus, 18703 Three Rivers Road, Covington, LA 70433, USA.

Viruses
|April 27, 2024
PubMed

Insights

T and B cells, but not NK cells, are crucial for controlling severe COVID-19 in a new mouse model. This finding highlights their importance in viral clearance and mitigating disease severity.

Area of Science:

  • Immunology
  • Virology
  • Pathogenesis of infectious diseases

Background:

  • Severe COVID-19 pathogenesis involves complex immune responses.
  • Understanding the roles of specific immune cells like T, B, and NK cells is critical.
  • Existing mouse models may not fully recapitulate severe human COVID-19 pathology.

Purpose of the Study:

  • To investigate the roles of T, B, and Natural Killer (NK) cells in severe COVID-19 pathogenesis.
  • To characterize a novel mouse-adapted SARS-CoV-2 (MA30) model for studying severe COVID-19.
  • To evaluate the MA30 mouse model by comparing it with existing models.

Main Methods:

  • Infection of C57BL/6 mice with SARS-CoV-2-MA30.
  • Comparison with SARS-CoV-2-WA1 infected K18-hACE2 mice.
  • Assessment of immune cell roles using Rag2-/- mice (lacking T and B cells) and NK cell depletion.

Main Results:

  • MA30-infected B6 mice exhibited severe peribronchial inflammation and pulmonary edema, mimicking human COVID-19 pathology.
  • Rag2-/- mice showed increased vulnerability and impaired viral clearance, indicating T and/or B cell essentiality.
  • NK cell depletion did not significantly impact disease severity in Rag2-/- mice, suggesting a minimal role in acute MA30 infection.

Conclusions:

  • T and/or B cells are essential for an effective immune response against SARS-CoV-2 in this model.
  • NK cells play a minimal role in the acute phase of MA30-induced disease.
  • The MA30 mouse model is a valuable tool for dissecting severe COVID-19 pathogenesis and immunology.
Keywords:
B cellsCOVID-19MA30NK cellsSARS-CoV-2T cells

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