Tissue-resident liver NK cell responses to MCMV infection

Abstract

Abstract Natural Killer (NK) cells belong to the ILC1 subgroup, which contains conventional NK (cNK) cells, ILC1 and tissue-resident NK (trNK) cells. The murine liver is home to both cNK cells and trNK cells. In this organ, cNK cells and trNK cells can be distinguished based on the expression of the transcription factors Eomes and T-bet. cNK cells are double positive for Eomes and T-bet while trNK cells do not express Eomes. During viral infection, the fate of the activated cNK cell population is relatively well defined. However, the fate of the trNK cell population remains unexplored. Using the MCMV model of infection, we found that a contraction phase precedes a replenishment of the trNK cell subset, which inversely correlates with cNK cell kinetics. We sought to determine whether the trNK cell response was a direct result of MCMV infection or an indirect response to inflammatory milieu. In order to help distinguish between these two possibilities, mice were injected with the iNKT ligand a-galactosylceramide (a-GalCer). We found that treatment with a-GalCer lead to an initial contraction phase of liver trNK cells, indicating that the phenotype observed is independent of MCMV infection. Altogether, these data suggest that liver cNK and trNK cell subsets, which arise from distinct developmental pathways, perform different functions in this organ.