老年人中流感诱导产生的干扰素-α存在缺陷。
Influenza-induced production of interferon-alpha is defective in geriatric individuals.
机构信息
Geriatric Research, Education and Clinical Center (GRECC), Cleveland VA Medical Center, Cleveland, OH 44106, USA.
出版信息
J Clin Immunol. 2010 May;30(3):373-83. doi: 10.1007/s10875-010-9374-9. Epub 2010 Feb 25.
BACKGROUND
The majority of deaths (90%) attributed to influenza are in person's age 65 or older. Little is known about whether defects in innate immune responses in geriatric individuals contribute to their susceptibility to influenza.
OBJECTIVE
Our aim was to analyze interferon-alpha (IFN-alpha) production in peripheral blood mononuclear cells (PBMCs) isolated from young and geriatric adult donors, stimulated with influenza A or Toll-like receptor (TLR) ligands. IFN-alpha is a signature anti-viral cytokine that also shapes humoral and cell-mediated immune responses.
RESULTS
Geriatric PBMCs produced significantly less IFN-alpha in response to live or inactivated influenza (a TLR7 ligand) but responded normally to CpG ODN (TLR9 ligand) and Guardiquimod (TLR7 ligand). All three ligands activate plasmacytoid dendritic cells (pDCs). While there was a modest decline in pDC frequency in older individuals, there was no defect in uptake of influenza by geriatric pDCs.
DISCUSSION AND CONCLUSION
Influenza-induced production of IFN-alpha was defective in geriatric PBMCs by a mechanism that was independent of reduced pDC frequency or viability, defects in uptake of influenza, inability to secrete IFN-alpha, or defects in TLR7 signaling.
背景
大多数（90%）与流感相关的死亡发生在 65 岁及以上的人群中。目前尚不清楚老年人先天免疫反应的缺陷是否导致他们易患流感。
目的
我们的目的是分析来自年轻和老年成年供体的外周血单核细胞（PBMC）在受到流感 A 或 Toll 样受体（TLR）配体刺激后产生的干扰素-α（IFN-α）。IFN-α 是一种标志性抗病毒细胞因子，也可调节体液和细胞免疫反应。
结果
老年 PBMC 对活流感或灭活流感（TLR7 配体）的反应产生的 IFN-α 明显减少，但对 CpG ODN（TLR9 配体）和 Guardiquimod（TLR7 配体）的反应正常。这三种配体均可激活浆细胞样树突状细胞（pDC）。虽然老年人 pDC 的频率略有下降，但流感在老年 pDC 中的摄取没有缺陷。
讨论与结论
流感诱导的 IFN-α产生在老年 PBMC 中存在缺陷，其机制与 pDC 频率或活力降低、流感摄取缺陷、不能分泌 IFN-α或 TLR7 信号转导缺陷无关。
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