适应性免疫细胞对于SARS-CoV-2诱导的病理是必要的
Brian Imbiakha1, Julie M Sahler1, David W Buchholz1
1Department of Microbiology and Immunology, Cornell University, College of Veterinary Medicine, Ithaca, NY 14853, USA.
Science advances
|January 3, 2024
概括
适应性免疫细胞,如B和T淋巴细胞,有助于严重的COVID-19症状. 虽然它们对于清除SARS-CoV-2至关重要,但它们的活性会增加小鼠的炎症和肺病理.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 病变的发生和发病.
背景情况:
- 严重急性呼吸道综合征冠状病毒2 (SARS-CoV-2) 导致全球大流行,人类患病率和死亡率显著.
- 目前尚不完全了解COVID-19病原和免疫失调背后的精确细胞机制.
研究的目的:
- 用小鼠模型研究适应性免疫细胞在SARS-CoV-2感染中的作用.
- 阐明COVID-19中炎症和病变的细胞机制.
主要方法:
- 在感染研究中使用了适应小鼠的SARS-CoV-2菌株 (MA10).
- 比较疾病进展,体重减轻和肺部病理在野生类型的鼠标, (缺乏B和T细胞),和αβT细胞缺乏的小鼠.
- 分析了炎症标记物 (介质素-6,瘤亡因子-α) 和中性粒细胞在肺组织中的透.
- 用T细胞和B细胞进行了采养转移实验,并将其转移到小鼠体内.
主要成果:
- 感染SARS-CoV-2的野生型小鼠在感染后3-4天内显著减肥 (~10%).
- 缺乏适应性免疫细胞的小鼠没有体重减轻,肺病理减少,中性粒细胞减少,IL-6和TNF-α水平降低.
- 缺乏αβ-T细胞的小鼠也表现出不那么严重的体重减轻.
- 将T细胞和B细胞收养转移到小鼠体内并没有显著改变保护性表型.
结论:
- 适应性免疫细胞,包括T和B淋巴细胞,在SARS-CoV-2感染期间在调解体重减轻和肺炎方面发挥着关键作用.
- 虽然对于病毒清除至关重要,但自适应性免疫反应有助于COVID-19的病理学增加.
- 针对适应性免疫调节可能提供治疗策略,以减轻COVID-19的严重程度.
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