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

Flommersfeld S, Böttcher JP, Ersching J, Flossdorf M, Meiser P, Pachmayr LO, Leube J, Hensel I, Jarosch S, Zhang Q, Chaudhry MZ, Andrae I, Schiemann M, Busch DH, Cicin-Sain L, Sun JC, Gasteiger G, Victora GD, Höfer T, Buchholz VR*, Grassmann S* (2021) Fate mapping of single NK cells identifies a type 1 innate lymphoid-like lineage that bridges innate and adaptive recognition of viral infection. Immunity. 2021 Aug 20:S1074-7613(21)00332-0. doi: 10.1016/j.immuni.2021.08.002. PMID: 34437840 *joint last authors (Projects B09 and B15)

Abstract cited directly from the article:

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.