Several groups have demonstrated that following engagement of TLR7, TLR8 or TLR9, pDCs from young individuals generate significantly more IFN-a, TNF-a and IL-6 than pDCs obtained from older adults [72,73,77,78]. This age-related reduction in TLR-induced cytokine production has been attributed to a decline in TLR expression and aberrant intracellular signalling [78 ] . For example, although not observed by all groups [79], ageing appears to be associated with reduced expression of TLR7 and TLR9 [72, 73], whilst impaired up-regulation of PI3-K and the transcription factor IFN regulatory factor-7 has been observed in TLR9-stimulated pDCs from aged donors [80].

Through the production of IFN-a, pDCs augment anti-viral immune responses by enhancing the cytotoxic activity of NK and CD8+ T cells. Thus, an age-related impairment in IFN-a secretion may contribute to the increased incidence of viral infections amongst older adults. Supporting this theory, Panda and co-workers found TLR-induced production of IFN-a by pDCs was significantly associated with both seroconversion and seroprotection following influenza vaccination in a cohort of young (21-30 years) and older (>65 years) adults [73], whilst Sridharan et al. demonstrated that via reduced production of IFN-a, pDCs from aged donors were unable to enhance the cytotoxicity of resting CD8+ T cells [79].

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