Tweet
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 1 , Julie M Sahler 1 , David W Buchholz 1 , Shahrzad Ezzatpour 2 , Mason Jager 3 , Annette Choi 1 , Isaac A Monreal 1 , Haewon Byun 1 , Richard Ayomide Adeleke 1 , Justin Leach 4 , Gary Whittaker 1 , Stephen Dewhurst 4 , Brian D Rudd 1 5 , Hector C Aguilar 1 5 , Avery August 1 5 6
Affiliations
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-/- 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-/- mice. Mice lacking αβ T cells also had less severe weight loss, but adoptive transfer of T and B cells into rag-/- 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.
. 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 1 , Julie M Sahler 1 , David W Buchholz 1 , Shahrzad Ezzatpour 2 , Mason Jager 3 , Annette Choi 1 , Isaac A Monreal 1 , Haewon Byun 1 , Richard Ayomide Adeleke 1 , Justin Leach 4 , Gary Whittaker 1 , Stephen Dewhurst 4 , Brian D Rudd 1 5 , Hector C Aguilar 1 5 , Avery August 1 5 6
Affiliations
- PMID: 38170764
- DOI: 10.1126/sciadv.adg5461
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-/- 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-/- mice. Mice lacking αβ T cells also had less severe weight loss, but adoptive transfer of T and B cells into rag-/- 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.