Loading…
Transcriptomic profiles of NK cell function indicate impaired responsiveness in chronic HIV-1 infection and enhanced functional activity post-vaccination
Natural Killer (NK) cells limit viral replication by direct recognition and killing of infected cells, performing Fc mediated ADCC and releasing cytokines to modulate other effector activity. Despite growing evidence that supports the importance of NK cells in HIV-1 disease progression, understandin...
Saved in:
Published in: | The Journal of immunology (1950) 2017-05, Vol.198 (1_Supplement), p.125-125.9 |
---|---|
Main Authors: | , , , , , , , , , , , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Summary: | Natural Killer (NK) cells limit viral replication by direct recognition and killing of infected cells, performing Fc mediated ADCC and releasing cytokines to modulate other effector activity. Despite growing evidence that supports the importance of NK cells in HIV-1 disease progression, understanding how these cells engage in vivo remains unclear. Here, we combined flow cytometry and gene expression analysis of NK cells responding to three in vitro models of NK stimulation to reveal distinct transcriptional profiles. While 76 gene transcripts were commonly upregulated following stimulation by direct cellular recognition, ADCC, and cytokine activation, 276, 36, and 293 genes were uniquely upregulated, respectively. Subsequently, a targeted gene expression panel was used to assess NK cell transcriptional content, directly ex vivo, in HIV-1 chronic infection. Transcriptional profiles in HIV-1 chronically infected individuals showed higher expression of genes associated with global activation and lower expression of genes associated with direct cell recognition and cytokine activation, compared to healthy individuals. We next looked at the transcriptional content of NK cells in response to MVA-CMDR vaccination, a live-attenuated viral vectored HIV-1 vaccine. NK cell transcriptional profiles of vaccinated individuals revealed upregulation of genes associated with direct cell recognition. These findings demonstrate that targeted transcriptional profiling provides a sensitive assessment of NK cell activity directly ex vivo that will improve our understanding of how NK cells respond to viral infections and after vaccination. |
---|---|
ISSN: | 0022-1767 1550-6606 |
DOI: | 10.4049/jimmunol.198.Supp.125.9 |