Single-cell analysis unravels the role of NK cells and monocytes in the control of SARS-CoV-2 breakthrough infections in vaccinated individuals

Analyzing the antiviral response of natural killer (NK) cells and monocytes is essential to understanding vaccine protection in an immunized population facing SARS-CoV-2 variant breakthrough infections (BTIs). In this study, in peripheral blood mononuclear cells (PBMCs) from vaccinated individuals with SARS-CoV-2 infections, we observed an increase in adaptive CD57⁺NKG2C⁺ NK cells and classical monocytes (CMs). Single-cell sequencing analysis showed that the transcriptomic profiles of IFN-induced IFIT3 and other IFN-stimulated genes exhibited marked upregulation in NK cells, defined as CD56^dimCD57⁺NKG2C⁺IFIT3⁺ NK cells. Additionally, CM in the blood showed characteristics indicative of differentiation into dendritic cells (DCs) and macrophages, which further evidenced their potential antiviral functions. Our study indicates that a vaccinated population rapidly activates an antiviral innate immune response following a BTI, thus revealing a link to the control of viral replication during SARS-CoV-2 BTIs.

解析自然杀伤（NK）细胞与单核细胞的抗病毒应答，对于阐明免疫人群遭遇新冠病毒（SARS-CoV-2）变异株突破感染（BTIs）时的疫苗保护效应具有重要意义。本研究针对发生新冠病毒感染的疫苗接种个体的外周血单个核细胞（PBMCs）开展分析，观察到适应性CD57+NKG2C+ NK细胞与经典单核细胞（CMs）的丰度升高。单细胞测序分析显示，在定义为CD56dimCD57+NKG2C+IFIT3+的NK细胞中，干扰素诱导的IFIT3及其他干扰素刺激基因的转录组特征呈现显著上调。此外，血液中的经典单核细胞表现出向树突状细胞（DCs）与巨噬细胞分化的特征，进一步印证了其潜在的抗病毒功能。本研究表明，免疫人群在发生突破感染后可快速激活抗病毒先天免疫应答，从而揭示了该应答与新冠病毒突破感染过程中病毒复制调控之间的关联。