Age-related differences in immune dynamics during SARS-CoV-2 infection in rhesus macaques.
Age-related differences in immune dynamics during SARS-CoV-2 infection in rhesus macaques.
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DOI：
10.26508/lsa.202101314
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发表时间：
2022-04
影响因子：
4.4
通讯作者：
de Wit E
中科院分区：
文献类型：
--
作者：
Speranza E;Purushotham JN;Port JR;Schwarz B;Flagg M;Williamson BN;Feldmann F;Singh M;Pérez-Pérez L;Sturdevant GL;Roberts LM;Carmody A;Schulz JE;van Doremalen N;Okumura A;Lovaglio J;Hanley PW;Shaia C;Germain RN;Best SM;Munster VJ;Bosio CM;de Wit E
年龄增长是严重COVID-19的风险因素。恒河猴的多组学分析表明，衰老可能会延迟或损害细胞免疫反应和免疫稳态的恢复。高龄是严重COVID-19的关键预测因素。为了深入了解这种关系，我们使用了SARS-CoV-2感染的恒河猴模型。8只年长和8只年轻的猕猴接种了SARS-CoV-2。使用病毒RNA定量、临床观察、胸部X线片、单细胞转录组学、多参数流式细胞术、多重免疫组织化学、细胞因子检测和脂质组学分析，在预定时间点在各种组织中评价动物。临床体征、肺浸润和病毒复制的差异有限。在3 dpi时支气管肺泡灌洗液中炎症相关基因的转录特征揭示了两个队列中先天免疫防御的有效安装。然而，年龄特异性免疫反应的分歧出现在急性期后。老年动物表现出持续的局部炎症先天性反应，而局部效应T细胞反应诱导较早的年轻动物。循环脂质介质和细胞因子水平突出了年轻动物中修复相关信号的增加，以及老年动物中持续的促炎反应。总之，尽管疾病结局相似，但多组学分析表明，年龄可能会延迟或损害抗病毒细胞免疫应答，并延迟有效恢复免疫稳态。
Increased age is a risk factor for severe COVID-19. Multi-omics profiling in rhesus macaques suggests that aging may delay or impair cellular immune responses and the return to immune homeostasis. Advanced age is a key predictor of severe COVID-19. To gain insight into this relationship, we used the rhesus macaque model of SARS-CoV-2 infection. Eight older and eight younger macaques were inoculated with SARS-CoV-2. Animals were evaluated using viral RNA quantification, clinical observations, thoracic radiographs, single-cell transcriptomics, multiparameter flow cytometry, multiplex immunohistochemistry, cytokine detection, and lipidomics analysis at predefined time points in various tissues. Differences in clinical signs, pulmonary infiltrates, and virus replication were limited. Transcriptional signatures of inflammation-associated genes in bronchoalveolar lavage fluid at 3 dpi revealed efficient mounting of innate immune defenses in both cohorts. However, age-specific divergence of immune responses emerged during the post-acute phase. Older animals exhibited sustained local inflammatory innate responses, whereas local effector T-cell responses were induced earlier in the younger animals. Circulating lipid mediator and cytokine levels highlighted increased repair-associated signals in the younger animals, and persistent pro-inflammatory responses in the older animals. In summary, despite similar disease outcomes, multi-omics profiling suggests that age may delay or impair antiviral cellular immune responses and delay efficient return to immune homeostasis.
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DOI：
10.4049/jimmunol.1201213
发表时间：
2013-02-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Brubaker AL;Rendon JL;Ramirez L;Choudhry MA;Kovacs EJ
通讯作者：
Kovacs EJ
影响因子：
46.9
作者：
Loske, J.;Roehmel, J.;Lehmann, I
通讯作者：
Lehmann, I
影响因子：
6
作者：
Bissel, Stephanie J.;Carter, Chalise E.;Ross, Ted M.
通讯作者：
Ross, Ted M.
影响因子：
--
作者：
Allen, Micah;Poggiali, Davide;Kievit, Rogier A
通讯作者：
Kievit, Rogier A
DOI：
10.1186/1742-4933-7-14
发表时间：
2010-10-20
期刊：
Immunity & ageing : I & A
影响因子：
--
作者：
Cusi MG;Martorelli B;Di Genova G;Terrosi C;Campoccia G;Correale P
通讯作者：
Correale P