Details

Autor(en) / Beteiligte

• Flommersfeld, Sophie
• Böttcher, Jan P.
• Ersching, Jonatan
• Flossdorf, Michael
• Meiser, Philippa
• Pachmayr, Ludwig O.
• Leube, Justin
• Hensel, Inge
• Jarosch, Sebastian
• Zhang, Qin
• Chaudhry, M. Zeeshan
• Andrae, Immanuel
• Schiemann, Matthias
• Busch, Dirk.H.
• Cicin-Sain, Luka
• Sun, Joseph C.
• Gasteiger, Georg
• Victora, Gabriel D.
• Höfer, Thomas
• Buchholz, Veit R.
• Grassmann, Simon

Titel

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

Ist Teil von

• Immunity (Cambridge, Mass.), 2021-10, Vol.54 (10), p.2288-2304.e7

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •Adaptive-like NK cell responses to MCMV encompass conventional and ILC1-like lineages•ILC1-like NK cells show enhanced cytokine production and splenic residency•ILC1-like NK cells show EOMES expression, target-specific cytotoxicity, and clonal expansion•ILC1-like NK cells drive cDC1 clustering and CD8+ T cell priming dependent on Ly49H and Batf3 Adaptive-like responses to MCMV are thought to originate from circulating conventional NK cells. Here, Flommersfeld et al. use single-cell fate mapping to show that a separate lineage of spleen-resident ILC1-like NK cells critically contributes to such responses. These ILC1-like NK cells induce cDC1 clustering and optimal CD8+ T cell priming, which depends on the transcription factor Batf3.