Section of Rheumatology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
J Infect Dis. 2011 May 15;203(10):1415-24. doi: 10.1093/infdis/jir048. Epub 2011 Mar 11.
West Nile virus (WNV), a mosquito-borne, single-stranded RNA flavivirus, causes significant human morbidity and mortality in the older population; thus, we investigated the effects of aging on infection with WNV in dendritic cells (DCs). We infected DCs with WNV in vitro and quantified cytokines and chemokines (type I IFN and CXCL10), pathogen recognition receptors RIG-I, and Toll-like receptors 3 and 7. The production of type I IFN was significantly lower in DCs from older donors, compared with younger donors. Although we observed no significant age-related difference in expression or nuclear translocation of signaling molecules in initial antiviral responses, DCs from older donors have diminished induction of late-phase responses (eg, STAT1, IRF7, and IRF1), suggesting defective regulation of type I IFN. Our results identify deficits in critical regulatory pathways in the antiviral response that may contribute to the enhanced susceptibility to viral infections observed in aging.
西尼罗河病毒（WNV）是一种由蚊子传播的单链 RNA 黄病毒，会导致老年人群体出现严重的发病率和死亡率；因此，我们研究了衰老对树突状细胞（DC）感染 WNV 的影响。我们在体外用 WNV 感染 DC，并定量分析细胞因子和趋化因子（I 型 IFN 和 CXCL10）、病原体识别受体 RIG-I 以及 Toll 样受体 3 和 7。与年轻供体相比，老年供体的 DC 产生的 I 型 IFN 明显减少。尽管我们在初始抗病毒反应中未观察到信号分子表达或核转位与年龄相关的显著差异，但老年供体的 DC 晚期反应（如 STAT1、IRF7 和 IRF1）的诱导减少，表明 I 型 IFN 的调节缺陷。我们的结果确定了抗病毒反应中关键调节途径的缺陷，这可能导致衰老过程中观察到的对病毒感染的易感性增强。
