Dendritic cells

Dendritic cells (DCs) are bone-marrow-derived antigen-presenting cells bridging innate and adaptive immunity. Two main subsets circulate in blood: plasmacytoid DCs (pDCs) detect viral nucleic acids via TLR7 and TLR9 and release type I interferons (IFN-α/β), while conventional myeloid DCs (cDCs) capture antigens, process them into peptides, and present these on MHC class I and II to prime CD8+ cytotoxic and CD4+ helper T cells. With age, pDC numbers decline — Jing et al. (2009) documented fewer circulating pDCs in healthy elderly donors, with reduced IFN-α secretion after influenza stimulation; cDCs remain numerically stable but show impaired antigen uptake and lower co-stimulatory expression (CD40, CD86). Aged DCs exhibit defective IRF-7 upregulation, reduced PI3-kinase activity, and — in respiratory tissue — elevated prostaglandin D2 blunting DC migration to draining lymph nodes during viral infection, impairing T-cell priming (Wong & Goldstein, 2013). Aged DCs also secrete less IL-10, release more pro-inflammatory cytokines, and lose capacity to induce regulatory T cells, driving loss of peripheral tolerance and inflammaging (Agrawal et al., 2017). The result is reduced vaccine immunogenicity; adjuvant approaches such as MF59 are under investigation but remain context-specific.