随着人类年龄的增长,对SARS-CoV-2的先天免疫反应的变化
Sudhanshu Agrawal1, Michelle Thu Tran1, Tara Sinta Kartika Jennings2
1Division of Basic and Clinical Immunology, Department of Medicine, University of California Irvine, Irvine, CA, 92697, USA.
老龄化会损害对像SARS-CoV-2这样的病毒的先天免疫反应,增加对严重COVID-19的易感性. 保护性抗病毒防御能力下降,而破坏性炎症增加,即使在中年人群中也是如此.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 老年学是指老年学的学科.
背景情况:
- 年龄增长是严重呼吸道病毒感染的重要危险因素,包括COVID-19.
- 天生的免疫力,对防御至关重要,随着年龄的增长而下降,影响整体免疫功能.
- 树突细胞 (DCs) 和巨细胞是感知病毒并启动适应反应的关键先天性免疫细胞.
研究的目的:
- 调查与 SARS-CoV-2 对天生的免疫反应的与年龄相关的变化.
- 确定导致老年人COVID-19严重程度增加的机制.
主要方法:
- 对来自年轻,中年和老年受试者的人类外周血液单核细胞 (PBMC) 的分析.
- 对树突细胞 (DC) 和单细胞激活的评估.
- 对细胞因子分泌的测量 (例如IL-29,CXCL-8,TREM-1).
- 免疫路径的基因表达分析.
主要成果:
- 随着年龄的增长,特别是pDCs中,SARS-CoV-2的DC和单细胞激活受到影响.
- 保护性IL-29的分泌量下降,而炎症调解剂CXCL-8和TREM-1随着年龄的增长而增加.
- 主体防御基因表达随着年龄的增长而下降,伴随着炎症途径的增加,即使在恒常状态下.
- 在老年人中,CD8 T细胞诱导受损,他们也显示出基线炎症的增加.
结论:
- 与年龄相关的天生的免疫失调,其特点是抗病毒反应减少和炎症增加,有助于COVID-19易感性.
- 这些免疫失调早在中年就开始了,这表明免疫保护能力的逐渐下降.
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