Читать книгу Vaccines for Older Adults: Current Practices and Future Opportunities - Группа авторов - Страница 16

DCs are key sources of inflammatory cytokines and costimulatory molecules that instruct the development of the adaptive antimicrobial immune response. Multiple classes of DCs exist, with the most common being myeloid DCs (mDCs) that activate naïve T cells, and plasmacytoid DCs (pDCs) which are major sources of IFNα following viral infection. DCs reside within lymph nodes or other tissues and survey the local microenvironment and then migrate to nearby lymph nodes that are being patrolled by adaptive immune cells. Recent studies using a unique resource of tissue acquisition from human organ donors have revealed that DC subset composition varies by tissue and age in humans, and these changes may impact site-specific immunity [37]. Both mDCs and pDCs from older donors show lower expression of TLRs globally and substantial decreases in cytokine production following TLR stimulation [38, 39]. Recent studies of DCs detected lower levels of RIG-I from older human subjects [40]. Similarly, pDCs and monocyte-derived DCs from healthy older subjects also secrete less IFN in response to IAV [41–43] and to WNV [38, 40]. DC production of type I IFN was significantly lower in older donors compared to younger donors, with diminished induction of late phase signaling responses, e.g. STAT1, IRF7, and IRF1, suggesting defective regulation of type I IFN induction [40]. IFN production by pDCs is decreased in older HSV-2-infected mice owing to impaired IRF7 upregulation upon viral infection, potentially further compromising antiviral immunity [44]. Multiple functional defects in these critical cells that bridge the innate and adaptive immune responses greatly contribute to impaired immune activation and responsiveness to infection in the elderly.