在严重的COVID-19疾病中,高水平的无细胞NKG2D-配体调节NKG2D表面表达,并损害NK细胞功能
Daniel Fernández-Soto1, Álvaro F García-Jiménez1, José M Casasnovas2
1Department of Immunology and Oncology, National Centre for Biotechnology (CNB), Spanish National Research Council (CSIC), Madrid, Spain.
Frontiers in immunology
|February 27, 2024
概括
在严重的COVID-19患者中,自然杀手 (NK) 细胞的功能减弱,这表明免疫监视缺陷而不是病原性作用. 这影响了对了解NK细胞参与SARS-CoV-2感染严重性的理解.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
背景情况:
- COVID-19的严重程度与免疫失调有关,但免疫细胞 (如NK细胞) 的特定作用仍然不清楚.
- 关于NK细胞在SARS-CoV-2免疫中是否具有保护性或致病性,存在相互矛盾的报道.
研究的目的:
- 研究不同COVID-19严重程度 (轻度与危及生命) 个体的NK细胞的表型和功能.
- 确定NK细胞改变对COVID-19疾病进展的贡献.
主要方法:
- 在轻度和重度的COVID-19患者中对NK细胞表型和功能的比较分析.
- 评估NK细胞激活,适应性NK细胞频率和抗体依赖细胞细胞毒性 (ADCC).
- 测量NK细胞上的NKG2D受体表达和患者血中可溶性NKG2D联结体 (NKG2DLs).
主要成果:
- 来自严重COVID-19患者的NK细胞表现出增加的激活和适应性NK细胞频率,但与轻度病例相比,ADCC功能降低.
- 在严重疾病患者中观察到NK细胞上NKG2D表达的丧失,与血NKG2DLs (ULBP2,ULBP3) 的升高相关.
- 实验室研究表明,NKG2DLs受损的NK细胞ADCC患者血清,可以被NKG2DL特异性抗体阻断.
结论:
- 在严重的COVID-19中减少NK细胞功能可能导致免疫监测受损和病毒复制增加.
- 异常的NK细胞功能不太可能驱动免疫病原性,而不是NK细胞介导的病毒控制中的缺陷.
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