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Impaired Interferon Signaling in Dendritic Cells From Older Donors Infected In Vitro With West Nile Virus

  作者 Qian, F; Wang, XM; Zhang, L; Lin, AP; Zhao, HY; Fikrig, E; Montgomery, RR  
  选自 期刊  Journal of Infectious Diseases;  卷期  2011年203-10;  页码  1415-1424  
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[摘要]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.

 
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