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感染SARS-CoV-2会损害NK细胞的功能
Marzena Lenart1, Magdalena Górecka1, Michal Bochenek2
1Virogenetics Laboratory of Virology, Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland.
Frontiers in immunology
|June 8, 2023
概括
SARS-CoV-2 感染通过降低 NK 细胞上的 CD161 表达的调节,损害了自然杀手 (NK) 细胞的功能. 这通过LLT1-CD161轴发生,这是在COVID-19患者中发现的一种新机制.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 细胞生物学 细胞生物学
背景情况:
- 自然杀手 (NK) 细胞对于控制病毒感染至关重要.
- COVID-19与免疫失调有关,包括NK细胞功能受损.
- 在SARS-CoV-2感染期间NK细胞抑制的精确机制尚未完全理解.
研究的目的:
- 研究SARS-CoV-2感染如何影响NK细胞表型和功能.
- 阐明SARS-CoV-2感染细胞和NK细胞之间的相互作用.
- 确定COVID-19中NK细胞抑制的新型机制.
主要方法:
- 与SARS-CoV-2感染的气道上皮细胞共培养NK细胞 (A549ACE2 / TMPRSS2细胞系和3D活体人体气道上皮模型).
- 分析NK细胞表面受体表达 (包括CD161).
- 在细胞上浮体,HAE基侧介质和患者血清中检测莱克样转录1 (LLT1).
- 用可溶性LLT1蛋白对NK细胞进行治疗.
主要成果:
- SARS-CoV-2 感染选择性地降低了 NK 细胞上的 CD161 表达,从而损害了它们的细胞毒性.
- SARS-CoV-2 感染在受感染的上皮细胞上升调 LLT1 连接体.
- 在患者血清中检测到LLT1.
- 可溶性LLT1蛋白降低了CD161+NK细胞,NK细胞的抗病毒活性和B粒酶的产生.
结论:
- 一种新的SARS-CoV-2介导的NK细胞抑制机制涉及LLT1-CD161轴.
- 这一途径有助于在COVID-19患者中观察到的免疫失调.
- 针对LLT1-CD161轴可能提供治疗潜力.
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