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

Cell Reports (Dec 2023)

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

Affiliations

Ciputra Adijaya Hartana: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA
Melanie Lancien: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA
Ce Gao: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA
Yelizaveta Rassadkina: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA
Mathias Lichterfeld: 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
Xu G. Yu: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Infectious Disease Division, Brigham and Women’s Hospital, Boston, MA 02115, USA; Corresponding author

Journal volume & issue: Vol. 42, no. 12
p. 113530

Abstract

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Summary: 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.

CP: Immunology

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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