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

Ciputra Adijaya Hartana; Melanie Lancien; Ce Gao; Yelizaveta Rassadkina; Mathias Lichterfeld; Xu G Yu

doi:10.1016/j.celrep.2023.113530

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.

Authors

Ciputra Adijaya Hartana¹, Melanie Lancien¹, Ce Gao¹, Yelizaveta Rassadkina¹, Mathias Lichterfeld², Xu G Yu³

Affiliations

¹ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
² Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Infectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
³ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Infectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA. Electronic address: xyu@mgh.harvard.edu.

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

Abstract

Publication types

MeSH terms

Substances

Grants and funding