Petrov Lev, Brumhard Sophia, Wisniewski Sebastian, Georg Philipp, Hillus David, Hiller Anna, Astaburuaga-García Rosario, Blüthgen Nils, Wyler Emanuel, Vogt Katrin, Dey Hannah-Philine, von Stillfried Saskia, Iwert Christina, Bülow Roman D, Märkl Bruno, Maas Lukas, Langner Christine, Meyer Tim, Loske Jennifer, Eils Roland, Lehmann Irina, Ondruschka Benjamin, Ralser Markus, Trimpert Jakob, Boor Peter, Bedoui Sammy, Meisel Christian, Mall Marcus A, Corman Victor M, Sander Leif Erik, Röhmel Jobst, Sawitzki Birgit
Berlin Institute of Health (BIH) at Charité, Charité - Universitätsmedizin Berlin, Berlin, Germany; Department of Infectious Diseases, Respiratory Medicine and Critical Care, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Cell Rep Med. 2025 Aug 19;6(8):102285. doi: 10.1016/j.xcrm.2025.102285.
Advanced age is the most important risk factor for severe disease or death from COVID-19, but a thorough mechanistic understanding of the molecular and cellular underpinnings is lacking. Multi-omics analysis of 164 samples from SARS-CoV-2-infected persons aged 1 to 84 years reveals a rewiring of type I interferon (IFN) signaling with a gradual shift from signal transducer and activator of transcription 1 (STAT1) to STAT3 activation in monocytes, CD4 T cells, and B cells with increasing age. Diversion of IFN signaling is associated with increased expression of inflammatory markers, enhanced release of inflammatory cytokines, and delayed contraction of infection-induced CD4 T cells. A shift from IFN-responsive germinal center B (GCB) cells toward CD69 GCB and atypical B cells during aging correlates with immunoglobulin (Ig)A production in children, whereas complement-fixing IgG predominates in adults. Our data provide a mechanistic basis for inflammation-prone responses to infections and associated pathology during aging.
高龄是感染新冠病毒后出现重症或死亡的最重要风险因素，但目前仍缺乏对其分子和细胞基础的全面机制性理解。对1至84岁新冠病毒感染者的164份样本进行的多组学分析显示，随着年龄增长，单核细胞、CD4 T细胞和B细胞中I型干扰素（IFN）信号通路发生重塑，信号转导和转录激活因子1（STAT1）的激活逐渐向STAT3转变。IFN信号通路的改变与炎症标志物表达增加、炎性细胞因子释放增强以及感染诱导的CD4 T细胞收缩延迟有关。衰老过程中，IFN反应性生发中心B（GCB）细胞向CD69 GCB和非典型B细胞转变，这与儿童免疫球蛋白（Ig）A的产生相关，而在成人中，补体结合性IgG占主导。我们的数据为衰老过程中对感染的易炎症反应及相关病理提供了机制基础。
