title: Impaired interferon signaling in dendritic cells from older donors infected in vitro with West Nile virus.
abstract: 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.
authors.affiliation: Section of Rheumatology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Qian
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Aiping
authors.initials: A
authors.lastname: Lin
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhao
authors.forename: Erol
authors.initials: E
authors.lastname: Fikrig
authors.forename: Ruth R
authors.initials: RR
authors.lastname: Montgomery
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D007372:Interferons / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction / Q000276:immunology*; D014901:West Nile Fever / Q000276:immunology*; D055815:Young Adult
chemical_list: D007372:Interferons