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

被引:4
作者
Imbiakha, Brian [1 ]
Sahler, Julie M. [1 ]
Buchholz, David W. [1 ]
Ezzatpour, Shahrzad [2 ]
Jager, Mason [3 ]
Choi, Annette [1 ]
Monreal, Isaac A. [1 ]
Byun, Haewon [1 ]
Adeleke, Richard Ayomide [1 ]
Leach, Justin [4 ]
Whittaker, Gary [1 ]
Dewhurst, Stephen [4 ]
Rudd, Brian D. [1 ,5 ,6 ]
Aguilar, Hector C. [1 ,5 ,6 ]
August, Avery [1 ,5 ,6 ,7 ]
机构
[1] Cornell Univ, Coll Vet Med, Dept Microbiol & Immunol, Ithaca, NY 14853 USA
[2] Cornell Univ, Coll Agr & Life Sci, Dept Microbiol, Ithaca, NY 14853 USA
[3] Cornell Univ, Coll Vet Med, Dept Biomed Sci, Ithaca, NY 14853 USA
[4] Univ Rochester, Dept Microbiol & Immunol, Rochester, NY 14642 USA
[5] Cornell Univ, Cornell Inst Host Microbe Interact & Def, Ithaca, NY 14853 USA
[6] Cornell Univ, Cornell Ctr Immunol, Ithaca, NY 14853 USA
[7] Cornell Univ, Cornell Ctr Hlth Equ, Ithaca, NY 14853 USA
基金
美国国家卫生研究院;
关键词
RECEPTOR; INNATE; BETA; IL-2; INFECTIONS; INTERFERON; ACTIVATION; MECHANISMS; TRANSGENE; CLEARANCE;
D O I
10.1126/sciadv.adg5461
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 similar to 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-alpha in rag(-/-) mice. Mice lacking alpha beta 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.
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页数:12
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