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Sci Adv . Adaptive immune cells are necessary for SARS-CoV-2-induced pathology

tetano

Editor, Senior Moderator
Sci Adv


. 2024 Jan 5;10(1):eadg5461.
doi: 10.1126/sciadv.adg5461. Epub 2024 Jan 3. Adaptive immune cells are necessary for SARS-CoV-2-induced pathology

Brian Imbiakha[SUP] 1 [/SUP], Julie M Sahler[SUP] 1 [/SUP], David W Buchholz[SUP] 1 [/SUP], Shahrzad Ezzatpour[SUP] 2 [/SUP], Mason Jager[SUP] 3 [/SUP], Annette Choi[SUP] 1 [/SUP], Isaac A Monreal[SUP] 1 [/SUP], Haewon Byun[SUP] 1 [/SUP], Richard Ayomide Adeleke[SUP] 1 [/SUP], Justin Leach[SUP] 4 [/SUP], Gary Whittaker[SUP] 1 [/SUP], Stephen Dewhurst[SUP] 4 [/SUP], Brian D Rudd[SUP] 1 5 [/SUP], Hector C Aguilar[SUP] 1 5 [/SUP], Avery August[SUP] 1 5 6 [/SUP]



Affiliations
Free article Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing the ongoing global pandemic associated with morbidity and mortality in humans. Although disease severity correlates with immune dysregulation, the cellular mechanisms of inflammation and pathogenesis of COVID-19 remain relatively poorly understood. Here, we used mouse-adapted SARS-CoV-2 strain MA10 to investigate the role of adaptive immune cells in disease. We found that while infected wild-type mice lost ~10% weight by 3 to 4 days postinfection, rag[SUP]-/-[/SUP] mice lacking B and T lymphocytes did not lose weight. Infected lungs at peak weight loss revealed lower pathology scores, fewer neutrophils, and lower interleukin-6 and tumor necrosis factor-α in rag[SUP]-/-[/SUP] mice. Mice lacking αβ T cells also had less severe weight loss, but adoptive transfer of T and B cells into rag[SUP]-/-[/SUP] mice did not significantly change the response. Collectively, these findings suggest that while adaptive immune cells are important for clearing SARS-CoV-2 infection, this comes at the expense of increased inflammation and pathology.


 
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