Aging impairs plasmacytoid dendritic cell function in response to TLR9 activation

Abstract

Plasmacytoid dendritic cells are innate sensors that produce IFNα in response to type A unmethylated CpG sequences or viral infections. However, the impact of aging on plasmacytoid dendritic cell function is unknown. Determining how aging alters the function of these cells may explain why older people are more susceptible to viral infections. Hence, we examined the effect of aging on plasmacytoid dendritic cell function in response to TLR9 stimulation with either type A CpG or herpes simplex virus type 2. We found that aged murine plasmacytoid dendritic cells produced lower levels of IFNα but preserved IL‐12p40 production after TLR9 activation as compared to young plasmacytoid dendritic cells. Transfer of young plasmacytoid dendritic cells into aged hosts recovered IFNα production and led to control of viremia during herpes simplex viral infection. We found that aged plasmacytoid dendritic cells manifested decreased gene expression of several signal adaptors, including interferon regulatory factor 7, which are critical for IFNα production during Toll‐like receptor activation. In sum, aging impairs the type 1 IFN‐signaling pathway in plasmacytoid dendritic cells, which may explain the increased susceptibility of older people to certain viral infections.This work was supported in part by NIH grants AG028082 and AG026772 to DRG. HWSD is supported by NIH grant T32AG019134. WEW is supported by NIH grant 5T32HL007778.