Type I IFN stimulates lymph node stromal cells from adult and old mice during a West Nile virus infection.
Type I IFN stimulates lymph node stromal cells from adult and old mice during a West Nile virus infection.
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由于与年龄相关的免疫反应下降，高龄是病毒感染期间的一个重要危险因素。老年人在感染西尼罗河病毒（WNV）后特别容易患严重的神经侵袭性疾病。先前的研究已经描述了西尼罗河病毒感染期间造血免疫细胞中与年龄相关的缺陷，最终导致抗病毒免疫力下降。位于引流淋巴结 (DLN) 免疫细胞之间的是非造血淋巴结基质细胞 (LNSC) 的结构网络。 LNSC 由众多不同的亚群组成，在协调强大的免疫反应中发挥着关键作用。 LNSCs 对 WNV 免疫和免疫衰老的贡献尚不清楚。在这里，我们检查了成人和老年 DLN 中 LNSC 对 WNV 的反应。急性西尼罗河病毒感染引发成人细胞浸润和 LNSC 扩张。相比之下，衰老的 DLN 表现出白细胞积累减少、LNSC 扩增延迟以及成纤维细胞和内皮细胞亚群组成改变（以 LEC 减少为标志）。我们建立了离体培养系统来探测 LNSC 功能。成人和老年 LNSC 均主要通过 I 型 IFN 信号传导识别持续的病毒感染。成年和老年 LNSC 的基因表达特征相似。研究发现，衰老的 LNSC 会持续上调立即早期反应基因。总的来说，这些数据表明 LNSC 对西尼罗河病毒感染有独特的反应。我们是第一个报告西尼罗河病毒感染期间 LNSC 群体和基因表达水平与年龄相关的差异的人。这些变化可能会损害抗病毒免疫力，导致老年人患西尼罗河病毒的几率增加。我们的研究描述了成年和老年小鼠中淋巴结基质细胞（LNSC）对西尼罗河病毒（WNV）的反应。体内 WNV 感染后，老化淋巴结表现出 LNSC 细胞结构减少和扩张。成人和老年 LNSC 以 I 型干扰素依赖性方式识别局部 WNV 感染，触发类似的抗病毒转录反应，然而，老年 LNSC 被发现组成性上调立即早期反应 (IER) 基因。
Advanced age is a significant risk factor during viral infection due to an age‐associated decline in the immune response. Older individuals are especially susceptible to severe neuroinvasive disease after West Nile virus (WNV) infection. Previous studies have characterized age‐associated defects in hematopoietic immune cells during WNV infection that culminate in diminished antiviral immunity. Situated amongst immune cells in the draining lymph node (DLN) are structural networks of nonhematopoietic lymph node stromal cells (LNSCs). LNSCs are comprised of numerous, diverse subsets, with critical roles in the coordination of robust immune responses. The contributions of LNSCs to WNV immunity and immune senescence are unclear. Here, we examine LNSC responses to WNV within adult and old DLNs. Acute WNV infection triggered cellular infiltration and LNSC expansion in adults. Comparatively, aged DLNs exhibited diminished leukocyte accumulation, delayed LNSC expansion, and altered fibroblast and endothelial cell subset composition, signified by fewer LECs. We established an ex vivo culture system to probe LNSC function. Adult and old LNSCs both recognized an ongoing viral infection primarily through type I IFN signaling. Gene expression signatures were similar between adult and old LNSCs. Aged LNSCs were found to constitutively upregulate immediate early response genes. Collectively, these data suggest LNSCs uniquely respond to WNV infection. We are the first to report age‐associated differences in LNSCs on the population and gene expression level during WNV infection. These changes may compromise antiviral immunity, leading to increased WNV disease in older individuals. Our study characterized lymph node stromal cell (LNSC) responses to West Nile virus (WNV) within adult and old mice. Aged lymph nodes display reduced LNSC cellularity and expansion following WNV infection in vivo. Adult and old LNSCs recognize local WNV infection in a type I interferon‐dependent manner where they trigger similar antiviral transcriptional responses, however, aged LNSCs were found to constitutively upregulate immediate early response (IER) genes.
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影响因子：
6.7
作者：
Lazear HM;Lancaster A;Wilkins C;Suthar MS;Huang A;Vick SC;Clepper L;Thackray L;Brassil MM;Virgin HW;Nikolich-Zugich J;Moses AV;Gale M Jr;Früh K;Diamond MS
通讯作者：
Diamond MS
影响因子：
7.8
作者：
Funk KE;Arutyunov AD;Desai P;White JP;Soung AL;Rosen SF;Diamond MS;Klein RS
通讯作者：
Klein RS
DOI：
10.1093/gerona/glz029
发表时间：
2019-11-01
影响因子：
5.1
作者：
Masters, April R.;Hall, Alexxus;Haynes, Laura
通讯作者：
Haynes, Laura
影响因子：
14.9
作者：
Chen J;Bardes EE;Aronow BJ;Jegga AG
通讯作者：
Jegga AG
影响因子：
32.4
作者：
Groom JR;Richmond J;Murooka TT;Sorensen EW;Sung JH;Bankert K;von Andrian UH;Moon JJ;Mempel TR;Luster AD
通讯作者：
Luster AD