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

Margaret C. Costanzo, Dohoon Kim, Matthew Creegan, Kerri G. Lal, Julie A. Ake, Jeffrey R. Currier, Hendrik Streeck, Merlin L. Robb, Nelson L. Michael, Diane L. Bolton, Nicholas J. Steers and Michael A. Eller ()
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Margaret C. Costanzo: Walter Reed Army Institute of Research
Dohoon Kim: Walter Reed Army Institute of Research
Matthew Creegan: Walter Reed Army Institute of Research
Kerri G. Lal: Walter Reed Army Institute of Research
Julie A. Ake: Walter Reed Army Institute of Research
Jeffrey R. Currier: Walter Reed Army Institute of Research
Hendrik Streeck: Walter Reed Army Institute of Research
Merlin L. Robb: Walter Reed Army Institute of Research
Nelson L. Michael: Walter Reed Army Institute of Research
Diane L. Bolton: Walter Reed Army Institute of Research
Nicholas J. Steers: Columbia University Medical Center
Michael A. Eller: Walter Reed Army Institute of Research

Nature Communications, 2018, vol. 9, issue 1, 1-16

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-03618-w

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