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

Authors
Type
Published Article
Journal
The Journal of Infectious Diseases
0022-1899
Publisher
Oxford University Press
Publication Date
Volume
203
Issue
10
Pages
1415–1424
Identifiers
DOI: 10.1093/infdis/jir048
PMID: 21398396
Source
Medline

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.

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