感染的巨细胞中的炎症酶激活导致COVID-19病理
Esen Sefik1, Rihao Qu1,2,3, Caroline Junqueira4,5,6
1Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
Nature
|April 28, 2022
概括
严重的COVID-19涉及由SARS-CoV-2感染的巨细胞驱动的肺炎. 激活炎细胞会导致细胞死亡,限制病毒的传播,但会增加炎症;阻止这种途径会逆转肺损伤,但会释放传染性病毒.
科学领域:
- 免疫学
- 病毒学
- 病理学
背景情况:
- 严重的COVID-19表现为持续的肺炎,细胞因子释放和持续的干扰素 (IFN) 反应.
- 一种人性化的小鼠模型 (MISTRG6-hACE2) 总结了严重的COVID-19病理的关键特征.
- 针对病毒复制或IFN途径的干预可以减轻该模型中的免疫过活化.
研究的目的:
- 调查肺内人类巨细胞在驱动严重的COVID-19病原体中的作用.
- 阐明SARS-CoV-2感染的巨细胞中炎酶激活和热死的机制.
- 评估针对COVID-19肺炎的炎症性途径的治疗潜力.
主要方法:
- 使用了感染SARS-CoV-2的MISTRG6-hACE2人性化小鼠模型.
- 分析了巨细胞的反应,包括炎酶激活,细胞因子释放 (IL-1,IL-18) 和热.
- 抑制NLRP3炎症途径以评估其对肺病理和病毒复制的影响.
主要成果:
- 肺部巨细胞的SARS-CoV-2感染会触发炎酶激活,IL-1/IL-18释放,并导致肺部炎症.
- 抑制NLRP3炎症途径可以逆转与严重COVID-19相关的慢性肺病理.
- 阻断炎酶激活有悖论地增加了感染的巨细胞中感染性SARS-CoV-2的释放.
结论:
- 人类肺部的巨细胞是通过炎症酶介导的炎症导致COVID-19严重肺炎的关键驱动因素.
- 炎症酶激活作为宿主防御机制,通过细胞因子释放和细胞死亡限制SARS-CoV-2的生产性病毒循环.
- 针对炎症细胞是一种复杂的治疗策略,有可能减少炎症,但有可能增加病毒分泌.
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