IL-15-dependent immune crosstalk between natural killer cells and dendritic cells in HIV-1 elite controllers

Cell Rep. 2023 Dec 26;42(12):113530. doi: 10.1016/j.celrep.2023.113530. Epub 2023 Dec 3.

Abstract

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.

Keywords: CP: Immunology; HIV infection; IL-15; NK cells; chromatin modifications; cytotoxicity; elite controllers; metabolism; trained innate immunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dendritic Cells / metabolism
  • Elite Controllers
  • HIV Infections*
  • HIV Seropositivity*
  • HIV-1*
  • Humans
  • Interleukin-15
  • Killer Cells, Natural

Substances

  • Interleukin-15