Aging impairs IFN regulatory factor 7 up-regulation in plasmacytoid dendritic cells during TLR9 activation.
Plasmacytoid dendritic cells (pDCs) are innate sensors that produce IFN-alpha in response to viral infections. Determining how aging alters the cellular and molecular function of these cells may provide an explanation of increased susceptibility of older people to viral infections. Hence, we examined whether aging critically impairs pDC function during infection with HSV-2, a viral pathogen that activates TLR9. We found that impaired IFN-alpha production by aged murine pDCs led to impaired viral clearance with aging. Upon TLR9 activation, aged pDCs displayed defective up-regulation of IFN-regulatory factor 7, a key adaptor in the type I IFN pathway, as compared with younger counterparts. Aged pDCs had more oxidative stress, and reducing oxidative stress in aged pDCs partly recovered the age-induced IFN-alpha defect during TLR9 activation. In sum, aging impairs the type I IFN pathway in pDCs, and this alteration may contribute to the increased susceptibility of older people to certain viral infections.
Stout-Delgado
Heather W
HW
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.
Yang
Xin
X
Walker
Wendy E
WE
Tesar
Bethany M
BM
Goldstein
Daniel R
DR
D000276:Adjuvants, Immunologic; D000375:Aging / Q000276:immunology*; D000818:Animals; D015153:Blotting, Western; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D050839:Interferon Regulatory Factor-7 / Q000096:biosynthesis* / Q000276:immunology; D016898:Interferon-alpha / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D017382:Reactive Oxygen Species; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051217:Toll-Like Receptor 9 / Q000276:immunology*; D015854:Up-Regulation; D014777:Virus Diseases / Q000276:immunology*
D000276:Adjuvants, Immunologic; D050839:Interferon Regulatory Factor-7; D016898:Interferon-alpha; C494235:Irf7 protein, mouse; D017382:Reactive Oxygen Species; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9