Pre-activated antiviral innate immunity in the upper airways controls early SARS-CoV-2 infection in children
Pre-activated antiviral innate immunity in the upper airways controls early SARS-CoV-2 infection in children
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DOI：
10.1038/s41587-021-01037-9
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发表时间：
2021-08-18
影响因子：
46.9
通讯作者：
Lehmann, I
中科院分区：
文献类型：
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作者：
Loske, J.;Roehmel, J.;Lehmann, I
单细胞测序显示，预激活免疫对儿童COVID-19轻度症状很重要。与成年人相比，儿童的严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）感染率降低，患2019年严重冠状病毒病的风险也大大降低。然而，在年轻人群中保护的分子机制仍然未知。在这里，我们描述了sars - cov -2阴性（n = 18）和年龄匹配的sars - cov -2阳性（n = 24）儿童和相应的成人样本（n = 44）上呼吸道的单细胞转录景观，涵盖了4周至77岁的年龄范围。儿童在上气道上皮细胞、巨噬细胞和树突状细胞中表现出更高的相关模式识别受体如MDA5 （IFIH1）和RIG-I （DDX58）的基础表达，导致对SARS-CoV-2感染的先天抗病毒反应比成人更强。我们进一步检测了不同的免疫细胞亚群，包括KLRC1 (NKG2A)（+）细胞毒性T细胞和CD8(+) T细胞群，其记忆表型主要发生在儿童中。我们的研究提供了证据，表明儿童的气道免疫细胞已经为病毒感知做好了准备，因此对SARS-CoV-2感染的早期先天抗病毒反应比成人更强。
Single-cell sequencing reveals pre-activated immunity as important for milder COVID-19 symptoms in children.Children have reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rates and a substantially lower risk for developing severe coronavirus disease 2019 compared with adults. However, the molecular mechanisms underlying protection in younger age groups remain unknown. Here we characterize the single-cell transcriptional landscape in the upper airways of SARS-CoV-2-negative (n = 18) and age-matched SARS-CoV-2-positive (n = 24) children and corresponding samples from adults (n = 44), covering an age range of 4 weeks to 77 years. Children displayed higher basal expression of relevant pattern recognition receptors such as MDA5 (IFIH1) and RIG-I (DDX58) in upper airway epithelial cells, macrophages and dendritic cells, resulting in stronger innate antiviral responses upon SARS-CoV-2 infection than in adults. We further detected distinct immune cell subpopulations including KLRC1 (NKG2A)(+) cytotoxic T cells and a CD8(+) T cell population with a memory phenotype occurring predominantly in children. Our study provides evidence that the airway immune cells of children are primed for virus sensing, resulting in a stronger early innate antiviral response to SARS-CoV-2 infection than in adults.