Responses of Dendritic Cells to TLR-4 Stimulation Are Maintained in the Elderly and Resist the Effects of CMV Infection Seen in the Young
Responses of Dendritic Cells to TLR-4 Stimulation Are Maintained in the Elderly and Resist the Effects of CMV Infection Seen in the Young
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DOI：
10.1093/gerona/glv119
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发表时间：
2016-09-01
影响因子：
5.1
通讯作者：
Pawelec, Graham
中科院分区：
文献类型：
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作者：
Janssen, Nicole;Derhovanessian, Evelyna;Pawelec, Graham
Toll样受体4（TLR-4）在一些年龄相关疾病的病理生理学中起着至关重要的作用。虽然有报道称老年人循环髓样树突状细胞（mDC）的功能较差，但缺乏老年人这些细胞中TLR-4功能的数据。在这里，我们研究了TLR-4的功能，在老年人中，通过离体分析的细胞因子的产生mDCs响应LPS在39个年轻人（23 - 34岁）和61个老年人（62-77岁）健康人使用流式细胞术。我们匹配这些受试者的巨细胞病毒（CMV）血清状态，因为这种普遍存在的疱疹病毒的潜伏感染已知会影响许多免疫参数。我们发现，TLR-4依赖的IL-6和TNF的产生强烈刺激循环中的mDCs从老年人。然而，超过一半的年轻捐助者的mDC未能以同样的方式作出反应。这与它们已经高度活化的离体状态有关，主要在CMV血清阳性的年轻供体中观察到，并与较低的CMV特异性IgG滴度相关。这可能反映了对终生控制CMV感染的日益重要的要求。这些数据表明，TLR-4激动剂可能是老年人的首选佐剂，他们中的大多数是CMV阳性，其免疫应答经常受损。
Toll-like receptor 4 (TLR-4) plays a crucial role in the pathophysiology of several age-related diseases. Although poorer function of circulating myeloid dendritic cells (mDCs) has been reported in the elderly, data on TLR-4 function in these cells in older people are lacking. Here, we investigated TLR-4 functionality in the elderly by ex vivo analysis of cytokine production of mDCs in response to LPS in 39 younger (2334 years) and 61 older (62-77 years) healthy people using flow cytometry. We matched these subjects for Cytomegalovirus (CMV)-serostatus because a latent infection with this ubiquitous herpesvirus is known to affect numerous immune parameters. We found that TLR-4-dependent production of IL-6 and TNF was strongly stimulated in circulating mDCs from the elderly. However, mDCs of more than half of the young donors failed to respond in the same way. This was related to their already highly activated ex vivo state, predominantly observed in CMV-seropositive young donors and associated with lower CMV-specific IgG titres. This may reflect an increasingly important requirement for control of CMV infection throughout life. These data suggest that TLR-4 agonists may be the adjuvants of choice for elderly people, most of whom are CMV-positive, and whose responses to immunization are frequently impaired.