Global analyses revealed age-related alterations in innate immune responses after stimulation of pathogen recognition receptors.
Global analyses revealed age-related alterations in innate immune responses after stimulation of pathogen recognition receptors.
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DOI：
10.1111/acel.12320
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发表时间：
2015-06
期刊：
影响因子：
7.8
通讯作者：
Haddad EK
中科院分区：
文献类型：
--
作者：
Metcalf TU;Cubas RA;Ghneim K;Cartwright MJ;Grevenynghe JV;Richner JM;Olagnier DP;Wilkinson PA;Cameron MJ;Park BS;Hiscott JB;Diamond MS;Wertheimer AM;Nikolich-Zugich J;Haddad EK
衰老导致免疫系统的多个组成部分失调，导致对感染的易感性增加，以及对老龄人口中的疫苗的反应不良。适应性B和T细胞的功能障碍已经有了很好的记录，但是衰老对先天免疫的影响仍然没有完全了解。使用外周血单核细胞（PBMC）的异质群体，我们首先进行了转录谱分析，发现与从成人（≤ 40岁）获得的细胞相比，从老年人（≥ 65岁）分离的PBMC对TLR 4、TLR 7/8和RIG-I激动剂刺激的反应延迟和改变。这种对先天免疫激动剂的延迟应答导致促炎和抗病毒细胞因子和趋化因子（包括TNFα、IL-6、IL-1β、IFNα、IFNγ、CCL 2和CCL 7）的产生减少。虽然主要的单核细胞和树突状细胞亚群并没有随着年龄的增长而发生变化，但特定细胞类型的激活发生了变化。来自老年受试者的PBMC还具有较低的CD 40+单核细胞频率，单核细胞和T细胞上的PD-L1上调受损，以及B细胞上的PD-L2和B7-H4表达增加。先天性激动剂的免疫应答缺陷对获得性免疫产生不利影响，因为在同种异体混合淋巴细胞反应（MLR）中，来自老年受试者的TLR刺激的PBMC（减去CD 3 T细胞）引起的成人T细胞增殖水平显著低于来自成人受试者的成人T细胞增殖水平。总的来说，这些与年龄相关的细胞因子、趋化因子和干扰素产生的变化以及共刺激蛋白表达可能导致对疫苗和感染的记忆B和T细胞免疫应答减弱。
Aging leads to dysregulation of multiple components of the immune system that results in increased susceptibility to infections and poor response to vaccines in the aging population. The dysfunctions of adaptive B and T cells are well documented, but the effect of aging on innate immunity remains incompletely understood. Using a heterogeneous population of peripheral blood mononuclear cells (PBMCs), we first undertook transcriptional profiling and found that PBMCs isolated from old individuals (≥ 65 years) exhibited a delayed and altered response to stimulation with TLR4, TLR7/8, and RIG-I agonists compared to cells obtained from adults (≤ 40 years). This delayed response to innate immune agonists resulted in the reduced production of pro-inflammatory and antiviral cytokines and chemokines including TNFα, IL-6, IL-1β, IFNα, IFNγ, CCL2, and CCL7. While the major monocyte and dendritic cell subsets did not change numerically with aging, activation of specific cell types was altered. PBMCs from old subjects also had a lower frequency of CD40+ monocytes, impaired up-regulation of PD-L1 on monocytes and T cells, and increased expression of PD-L2 and B7-H4 on B cells. The defective immune response to innate agonists adversely affected adaptive immunity as TLR-stimulated PBMCs (minus CD3 T cells) from old subjects elicited significantly lower levels of adult T-cell proliferation than those from adult subjects in an allogeneic mixed lymphocyte reaction (MLR). Collectively, these age-associated changes in cytokine, chemokine and interferon production, as well as co-stimulatory protein expression could contribute to the blunted memory B- and T-cell immune responses to vaccines and infections.
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影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
DOI：
10.1046/j.1532-5415.2003.51465.x
发表时间：
2003-10-01
影响因子：
6.3
作者：
Borson, S;Scanlan, JM;Ganguli, M
通讯作者：
Ganguli, M
影响因子：
5.3
作者：
Leng, QB;Bentwich, Z;Borkow, G
通讯作者：
Borkow, G
影响因子：
32.4
作者：
Jego, G;Palucka, AK;Banchereau, J
通讯作者：
Banchereau, J
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y