Aging alters antiviral signaling pathways resulting in functional impairment in innate immunity in response to pattern recognition receptor agonists.
Aging alters antiviral signaling pathways resulting in functional impairment in innate immunity in response to pattern recognition receptor agonists.
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DOI：
10.1007/s11357-022-00612-5
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发表时间：
2022-10
期刊：
影响因子：
5.6
通讯作者：
Haddad, Elias K.
中科院分区：
文献类型：
--
作者：
Connors, Jennifer;Taramangalam, Bhavani;Cusimano, Gina;Bell, Matthew R.;Matt, Stephanie M.;Runner, Kaitlyn;Gaskill, Peter J.;DeFilippis, Victor;Nikolich-Zugich, Janko;Kutzler, Michele A.;Haddad, Elias K.
随着世界人口向老年人（> 65岁）比例的增加转变，对病原体和疫苗的免疫力随着老龄化而逐渐受损是一个重大的公共卫生问题。我们以前已经证明，与来自成年受试者的细胞相比，来自老年志愿者的细胞对TLR配体的I型干扰素和T细胞和B细胞辅助细胞因子的诱导延迟和缺陷。然而，潜在的细胞内机制没有得到很好的描述。在此，我们研究了在I型干扰素（IFN）的产生中重要的两个关键途径，干扰素应答因子7（pIRF 7）和TANK结合激酶（pTBK-1）。我们发现，与年轻个体（n = 11）相比，在用通路特异性激动剂刺激后，来自老年人（n = 11）的交叉致敏树突状细胞（cDC 1 s）、CD 4 + T细胞致敏DC（cDC 2s）和CD 14 dimCD 16+血管巡逻单核细胞中pIRF 7和pTBK-1减少。这些关键抗病毒途径蛋白的减少与吞噬作用的减少相关，表明功能受损。总的来说，我们的研究结果描述了解释老年人先天性功能障碍的分子机制，从而可以为我们提供恢复这些缺陷的新方法。在线版本包含补充材料，可通过10.1007/s11357-022-00612-5获得。
The progressive impairment of immunity to pathogens and vaccines with aging is a significant public health problem as the world population shifts to an increased percentage of older adults (> 65). We have previously demonstrated that cells obtained from older volunteers have delayed and defective induction of type I interferons and T cell and B cell helper cytokines in response to TLR ligands when compared to those from adult subjects. However, the underlying intracellular mechanisms are not well described. Herein, we studied two critical pathways important in the production of type I interferon (IFN), the interferon response factor 7 (pIRF7), and TANK-binding kinase (pTBK-1). We show a decrease in pIRF7 and pTBK-1 in cross-priming dendritic cells (cDC1s), CD4+ T cell priming DCs (cDC2s), and CD14dimCD16+ vascular patrolling monocytes from older adults (n = 11) following stimulation with pathway-specific agonists in comparison with young individuals (n = 11). The decrease in these key antiviral pathway proteins correlates with decreased phagocytosis, suggesting impaired function in Overall, our findings describe molecular mechanisms which explain the innate functional impairment in older adults and thus could inform us of novel approaches to restore these defects. The online version contains supplementary material available at 10.1007/s11357-022-00612-5.
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影响因子：
32.4
作者：
Alameh MG;Tombácz I;Bettini E;Lederer K;Sittplangkoon C;Wilmore JR;Gaudette BT;Soliman OY;Pine M;Hicks P;Manzoni TB;Knox JJ;Johnson JL;Laczkó D;Muramatsu H;Davis B;Meng W;Rosenfeld AM;Strohmeier S;Lin PJC;Mui BL;Tam YK;Karikó K;Jacquet A;Krammer F;Bates P;Cancro MP;Weissman D;Luning Prak ET;Allman D;Locci M;Pardi N
通讯作者：
Pardi N
影响因子：
7.3
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Oshiumi H
影响因子：
24.8
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通讯作者：
Eisenbarth SC
影响因子：
20.3
作者：
Delneste, Y;Charbonnier, P;Jeannin, P
通讯作者：
Jeannin, P
影响因子：
32.4
作者：
Guilliams M;Dutertre CA;Scott CL;McGovern N;Sichien D;Chakarov S;Van Gassen S;Chen J;Poidinger M;De Prijck S;Tavernier SJ;Low I;Irac SE;Mattar CN;Sumatoh HR;Low GHL;Chung TJK;Chan DKH;Tan KK;Hon TLK;Fossum E;Bogen B;Choolani M;Chan JKY;Larbi A;Luche H;Henri S;Saeys Y;Newell EW;Lambrecht BN;Malissen B;Ginhoux F
通讯作者：
Ginhoux F