Impaired interferon signaling in dendritic cells from older donors infected in vitro with West Nile virus

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / immunology*
  • Dendritic Cells / immunology*
  • Female
  • Humans
  • Interferons / physiology*
  • Leukocytes, Mononuclear / immunology
  • Male
  • Middle Aged
  • Signal Transduction / immunology*
  • West Nile Fever / immunology*
  • Young Adult


  • Interferons