Upon viral infection, natural killer (NK) cells expressing certain germline-encoded receptors are selected, expanded, and maintained in an adaptive-like manner. Currently, these are thought to differentiate along a common pathway. However, by fate mapping of single NK cells upon murine cytomegalovirus (MCMV) infection, we identified two distinct NK cell lineages that contributed to adaptive-like responses. One was equivalent to conventional NK (cNK) cells while the other was transcriptionally similar to type 1 innate lymphoid cells (ILC1s). ILC1-like NK cells showed splenic residency and strong cytokine production but also recognized and killed MCMV-infected cells, guided by activating receptor Ly49H. Moreover, they induced clustering of conventional type 1 dendritic cells and facilitated antigen-specific T cell priming early during MCMV infection, which depended on Ly49H and the NK cell-intrinsic expression of transcription factor Batf3. Thereby, ILC1-like NK cells bridge innate and adaptive viral recognition and unite critical features of cNK cells and ILC1s.

在病毒感染后，表达某些种系编码受体的自然杀伤 (NK) 细胞会以适应性样方式被选择、扩增和维持。目前，这些被认为是沿着一个共同的途径进行区分的。然而，通过小鼠巨细胞病毒 (MCMV) 感染后单个 NK 细胞的命运图谱，我们确定了两种不同的 NK 细胞谱系，它们有助于适应性样反应。一个相当于传统的 NK (cNK) 细胞，而另一个在转录上类似于 1 型先天淋巴细胞 (ILC1s)。在激活受体 Ly49H 的引导下，ILC1 样 NK 细胞显示出脾内驻留和强烈的细胞因子产生，但也识别和杀死 MCMV 感染的细胞。此外，它们诱导常规 1 型树突状细胞聚集，并在 MCMV 感染早期促进抗原特异性 T 细胞启动，这取决于 Ly49H 和转录因子 Batf3 的 NK 细胞内在表达。因此，ILC1 样 NK 细胞桥接了先天性和适应性病毒识别，并结合了 cNK 细胞和 ILC1 的关键特征。