Abstract
The aging process is accompanied by altered immune system functioning and an increased risk of infection. Dendritic cells (DCs) are antigen-presenting cells that play a key role in both adaptive and innate immunity, but how aging affects DCs and their influence on immunity has not been thoroughly established. Here we examined the function of conventional DCs (cDCs) in old mice after TLR7 stimulation, focusing on their ability to cross-prime CD8+ T cells. Using polyU, a synthetic ssRNA analog, as TLR7 ligand and OVA as an antigen (Ag) model, we found that cDCs from old mice have a poor ability to stimulate a CD8+ T cell-mediated cytotoxic response. cDCs from old mice exhibit alterations in Ag-processing machinery and TLR7 activation. Remarkably, CD8α+ cDCs from old mice have an impaired ability to activate naïve CD8+ T cells and, moreover, a lower capacity to mature and to process exogenous Ag. Taken together, our results suggest that immunosenescence impacts cDC function, affecting the activation of naïve CD8+ T cells and the generation of effector cytotoxic T cells.
Highlights
Aging impacts the homeostatic function of many systems, including the immune system, leading to a reduced ability to mount a robust immune response, in a process called immunosenescence [1,2,3]
We examined the effects of aging on the ability of conventional DCs (cDCs) to cross-present exogenous Ag to CD8+ T cells and to induce cross-priming after TLR7 stimulation
Representative dot plots with gating strategy from young mice are shown in S2A and S2C Fig. We found a significant decrease in CD8α+ cDC number and frequency in the spleen of old mice compared to the young ones (S2B Fig). plasmacytoid DCs (pDCs) subsets decreased in frequency but not in number and the CD8α- cDCs’ number and frequency were unaffected by aging
Summary
Aging impacts the homeostatic function of many systems, including the immune system, leading to a reduced ability to mount a robust immune response, in a process called immunosenescence [1,2,3]. Such changes in immune function result in increased susceptibility to and severity of viral and bacterial infections, increased incidence of cancer and autoimmune diseases, and a poor response to vaccination in the elderly [4,5,6,7,8,9]. Dendritic cells (DCs) are Ag-presenting cells (APCs) that play a key role in PLOS ONE | DOI:10.1371/journal.pone.0140672 October 16, 2015
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