Natural Killer Cells Do Not Attenuate a Mouse-Adapted SARS-CoV-2-Induced Disease in <i>Rag2</i><sup>−/−</sup> Mice
Calder R Ellsworth,
Chenxiao Wang,
Alexis R Katz,
Zheng Chen,
Mohammad Islamuddin,
Haoran Yang,
Sarah E Scheuermann,
Kelly A Goff,
Nicholas J Maness,
Robert V Blair,
Jay K Kolls,
Xuebin Qin
Affiliations
Calder R Ellsworth
Division of Comparative Pathology, Tulane National Primate Research Center, Health Sciences Campus, 18703 Three Rivers Road, Covington, LA 70433, USA
Chenxiao Wang
Division of Comparative Pathology, Tulane National Primate Research Center, Health Sciences Campus, 18703 Three Rivers Road, Covington, LA 70433, USA
Alexis R Katz
Departments of Medicine and Pediatrics, Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, LA 70112, USA
Zheng Chen
Division of Comparative Pathology, Tulane National Primate Research Center, Health Sciences Campus, 18703 Three Rivers Road, Covington, LA 70433, USA
Mohammad Islamuddin
Division of Comparative Pathology, Tulane National Primate Research Center, Health Sciences Campus, 18703 Three Rivers Road, Covington, LA 70433, USA
Haoran Yang
Departments of Medicine and Pediatrics, Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, LA 70112, USA
Sarah E Scheuermann
Division of Comparative Pathology, Tulane National Primate Research Center, Health Sciences Campus, 18703 Three Rivers Road, Covington, LA 70433, USA
Kelly A Goff
Division of Comparative Pathology, Tulane National Primate Research Center, Health Sciences Campus, 18703 Three Rivers Road, Covington, LA 70433, USA
Nicholas J Maness
Division of Comparative Pathology, Tulane National Primate Research Center, Health Sciences Campus, 18703 Three Rivers Road, Covington, LA 70433, USA
Robert V Blair
Division of Comparative Pathology, Tulane National Primate Research Center, Health Sciences Campus, 18703 Three Rivers Road, Covington, LA 70433, USA
Jay K Kolls
Departments of Medicine and Pediatrics, Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, LA 70112, USA
Xuebin Qin
Division of Comparative Pathology, Tulane National Primate Research Center, Health Sciences Campus, 18703 Three Rivers Road, Covington, LA 70433, USA
This study investigates the roles of T, B, and Natural Killer (NK) cells in the pathogenesis of severe COVID-19, utilizing mouse-adapted SARS-CoV-2-MA30 (MA30). To evaluate this MA30 mouse model, we characterized MA30-infected C57BL/6 mice (B6) and compared them with SARS-CoV-2-WA1 (an original SARS-CoV-2 strain) infected K18-human ACE2 (K18-hACE2) mice. We found that the infected B6 mice developed severe peribronchial inflammation and rapid severe pulmonary edema, but less lung interstitial inflammation than the infected K18-hACE2 mice. These pathological findings recapitulate some pathological changes seen in severe COVID-19 patients. Using this MA30-infected mouse model, we further demonstrate that T and/or B cells are essential in mounting an effective immune response against SARS-CoV-2. This was evident as Rag2−/− showed heightened vulnerability to infection and inhibited viral clearance. Conversely, the depletion of NK cells did not significantly alter the disease course in Rag2−/− mice, underscoring the minimal role of NK cells in the acute phase of MA30-induced disease. Together, our results indicate that T and/or B cells, but not NK cells, mitigate MA30-induced disease in mice and the infected mouse model can be used for dissecting the pathogenesis and immunology of severe COVID-19.
