Department of Microbiology and Immunology, Cornell University, College of Veterinary Medicine, Ithaca, NY 14853, USA.
Department of Microbiology, Cornell University, College of Agriculture and Life Sciences, Ithaca, NY 14853, USA.
Sci Adv. 2024 Jan 5;10(1):eadg5461. doi: 10.1126/sciadv.adg5461. Epub 2024 Jan 3.
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, 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 mice. Mice lacking αβ T cells also had less severe weight loss, but adoptive transfer of T and B cells into 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.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）正在引发与人类发病率和死亡率相关的持续全球大流行。尽管疾病的严重程度与免疫失调相关，但 COVID-19 的炎症发生机制和发病机制仍相对了解甚少。在这里，我们使用小鼠适应的 SARS-CoV-2 株 MA10 来研究适应性免疫细胞在疾病中的作用。我们发现，虽然感染野生型小鼠在感染后 3 至 4 天体重减轻约 10%，但缺乏 B 和 T 淋巴细胞的小鼠体重并未减轻。在体重减轻达到峰值时，感染的肺部显示出较低的病理学评分、较少的中性粒细胞以及较低的白细胞介素 6 和肿瘤坏死因子-α。缺乏 αβ T 细胞的小鼠的体重减轻也不那么严重，但将 T 和 B 细胞过继转移到 小鼠中并没有显著改变反应。总的来说，这些发现表明，虽然适应性免疫细胞对于清除 SARS-CoV-2 感染很重要，但这是以增加炎症和病理学为代价的。
