■可以保护2019年冠状病毒病(COVID-19)儿童免受严重或致命疾病的免疫学特征尚未完全了解。
■这里,我们对15名儿童(8名COVID-19患者)的外周血样本进行了单细胞RNA测序(scRNA-seq)分析,并与18名成人(13名COVID-19患者)进行了比较.
■儿童-成人整合的单细胞数据表明,在大多数主要免疫细胞类型中,患有该疾病的儿童对I型干扰素的反应受限,同时抑制上游干扰素调节因子和单核细胞中Toll样受体的表达,这通过体外干扰素刺激试验得到证实。与成年患者不同,患有COVID-19的儿童显示激活的促炎CD14单核细胞的频率较低,可能解释了细胞因子风暴的稀缺性。值得注意的是,自然杀伤(NK)细胞在儿科患者表现出强大的细胞毒性与细胞毒性分子的丰富表达和上调的细胞毒性途径,而细胞衰老,以及Notch信号通路,在NK细胞中显著下调,所有这些都表明儿童NK细胞的细胞毒性比成人患者更强烈,CD107a脱颗粒测定进一步证实了这一点。最后,适度的适应性免疫应答是明显的,与成人患者相比,儿童患者的幼稚T细胞较多,但活化和增殖的T细胞较少,而幼稚B细胞较少,但活化的B细胞较多.
■最后,这项初步研究揭示了主要免疫细胞类型的不同细胞频率和激活状态,尤其是PBMC中更强烈的NK细胞毒性,这可能有助于保护儿童免受严重COVID-19的侵害。
UNASSIGNED: The immunological characteristics that could protect children with coronavirus disease 2019 (COVID-19) from severe or fatal illnesses have not been fully understood yet.
UNASSIGNED: Here, we performed single-cell RNA sequencing (scRNA-seq) analysis on peripheral blood samples of 15 children (8 with COVID-19) and compared them to 18 adults (13 with COVID-19).
UNASSIGNED: The child-adult integrated single cell data indicated that children with the disease presented a restrained response to type I interferon in most of the major immune cell types, along with suppression of upstream interferon regulatory factor and toll-like receptor expression in monocytes, which was confirmed by in vitro interferon stimulation assays. Unlike adult patients, children with COVID-19 showed lower frequencies of activated proinflammatory CD14+ monocytes, possibly explaining the rareness of cytokine storm in them. Notably, natural killer (NK) cells in pediatric patients displayed potent cytotoxicity with a rich expression of cytotoxic molecules and upregulated cytotoxic pathways, whereas the cellular senescence, along with the Notch signaling pathway, was significantly downregulated in NK cells, all suggesting more robust cytotoxicity in NK cells of children than adult patients that was further confirmed by CD107a degranulation assays. Lastly, a modest adaptive immune response was evident with more naïve T cells but less activated and proliferated T cells while less naïve B cells but more activated B cells in children over adult patients.
UNASSIGNED: Conclusively, this preliminary study revealed distinct cell frequency and activation status of major immune cell types, particularly more robust NK cell cytotoxicity in PBMC that might help protect children from severe COVID-19.