%0 Journal Article
%T IL-15-dependent immune crosstalk between natural killer cells and dendritic cells in HIV-1 elite controllers.
%A Hartana CA
%A Lancien M
%A Gao C
%A Rassadkina Y
%A Lichterfeld M
%A Yu XG
%J Cell Rep
%V 42
%N 12
%D 2023 12 26
%M 38048223
暂无%R 10.1016/j.celrep.2023.113530
%X As the principal effector cell population of the innate immune system, natural killer (NK) cells may make critical contributions to natural, immune-mediated control of HIV-1 replication. Using genome-wide assessments of activating and inhibitory chromatin features, we demonstrate here that cytotoxic NK (cNK) cells from elite controllers (ECs) display elevated activating histone modifications at the interleukin 2 (IL-2)/IL-15 receptor β chain and the BCL2 gene loci. These histone changes translate into increased responsiveness of cNK cells to paracrine IL-15 secretion, which coincides with higher levels of IL-15 transcription by myeloid dendritic cells in ECs. The distinct immune crosstalk between these innate immune cell populations results in improved IL-15-dependent cNK cell survival and cytotoxicity, paired with a metabolic profile biased toward IL-15-mediated glycolytic activities. Together, these results suggest that cNK cells from ECs display a programmed IL-15 response signature and support the emerging role of innate immune pathways in natural, drug-free control of HIV-1.