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IL-15-DEPENDENT IMMUNE CROSS-TALK BETWEEN NK CELLS AND DENDRITIC CELLS IN HIV-1 ELITE CONTROLLERS [CUT&RUN]

ABSTRACT: As the principal effector cell population of the innate immune system, NK cells may make critical contributions to natural, immune-mediated control of HIV-1 replication. Using genome-wide assessments of activating and inhibitory epigenetic chromatin features, we here demonstrate that cytotoxic NK (cNK) cells from elite controllers (ECs) frequently display elevated activating histone modifications at the IL-2/IL-15 receptor β chain and the BCL-2 gene loci. These epigenetic changes translated into increased responsiveness of cNK cells to paracrine IL-15 secretion, which coincided with higher levels of IL-15 transcription by myeloid dendritic cells in ECs. The distinct immune crosstalk between these two innate immune cell populations resulted in improved IL-15-dependent cNK cell survival, paired with a metabolic profile biased towards IL-15-mediated glycolytic activities. Together, these results suggest that cNK cells from ECs display an epigenetically-programmed IL-15 response signature, and support the emerging role of innate immune pathways in natural, drug-free control of HIV-1.

ORGANISM(S): Homo sapiens

PROVIDER: GSE232915 | GEO | 2023/12/06

REPOSITORIES: GEO

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