Fate mapping of single NK cells identifies a type 1 innate lymphoid-like lineage that bridges innate and adaptive recognition of viral infection [bulk_RNAseq_d8pi]

Upon viral infection, 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. CD27+ CD62L- and CD27- CD62L+ Ly49H+ NK cells were sorted and adoptively transferred into Rag2-/- Il2rg-/- mice infected with MCMV. At day 8 p.i., CD27+ CD62L- and CD27- CD62L- cells were sorted from progenies of CD27+ CD62L- cells and CD27- CD62L+ and CD27- CD62L- were sorted from progenies of CD27- CD62L+ cells in spleen. 2x 500 cells were sorted from each population and bulk RNA-Seq was performed of all samples.