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Nat Commun. 2018 Mar 23;9(1):1212. doi: 10.1038/s41467-018-03618-w.

Transcriptomic signatures of NK cells suggest impaired responsiveness in HIV-1 infection and increased activity post-vaccination.

Author information

1
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, 503 Robert Grant Ave., Silver Spring, MD, 20901, USA.
2
Henry M. Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Dr., Bethesda, MD, 20817, USA.
3
Virus Diseases Branch, Walter Reed Army Institute of Research, 503 Robert Grant Ave., Silver Spring, MD, 20901, USA.
4
Institute for HIV Research, University Hospital Essen, University Duisburg-Essen, 45147, Essen, Germany.
5
Division of Nephrology, Columbia University Medical Center, 1150 St. Nicholas Ave., New York, NY, 10032, USA.
6
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, 503 Robert Grant Ave., Silver Spring, MD, 20901, USA. meller@hivresearch.org.
7
Henry M. Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Dr., Bethesda, MD, 20817, USA. meller@hivresearch.org.

Abstract

Natural killer (NK) cells limit viral replication by direct recognition of infected cells, antibody-dependent cellular cytotoxicity (ADCC), and releasing cytokines. Although growing evidence supports NK cell antiviral immunity in HIV-1 infection, further knowledge of their response is necessary. Here we show that NK cells responding to models of direct cell recognition, ADCC, and cytokine activation have unique transcriptional fingerprints. Compared with healthy volunteers, individuals with chronic HIV-1 infection have higher expression of genes commonly associated with activation, and lower expression of genes associated with direct cell recognition and cytokine stimulation in their NK cells. By contrast, NK cell transcriptional profiles of individuals receiving a modified vaccinia Ankara (MVA) vectored HIV-1 vaccine show upregulation of genes associated with direct cell recognition. These findings demonstrate that targeted transcriptional profiling provides a sensitive assessment of NK cell activity, which helps understand how NK cells respond to viral infections and vaccination.

PMID:
29572470
PMCID:
PMC5865158
DOI:
10.1038/s41467-018-03618-w
[Indexed for MEDLINE]
Free PMC Article

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