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.
Highlights
Natural killer (NK) cells limit viral replication by direct recognition of infected cells, antibodydependent cellular cytotoxicity (ADCC), and releasing cytokines
Robust activation of NK cells, calculated as total expression of CD107a, interferon (IFN)-γ, and tumor necrosis factor (TNF), was observed with an average 30%, 30%, and 8% of NK cells responding to K562, an ADCC mimic, and cytokine stimulation, respectively
Upregulation of CD107a was different between the cell-based stimulation and cytokine stimulation (Fig. 1b)
Summary
Natural killer (NK) cells limit viral replication by direct recognition of infected cells, antibodydependent cellular cytotoxicity (ADCC), and releasing cytokines. 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. NK cells possess diverse capacity to respond to a variety of pathologic and inflammatory conditions, including HIV-1, yet more information is needed to better understand the underlying framework for their effector function and how these cells may impact outcome With this combined information, opportunities to direct and exploit NK cell antiviral immunity to target HIV have exponentially grown[17]. Utilizing cell sorting and transcriptional profiling to identify unique transcripts and distinct biological pathways can unveil potential mechanisms by which NK cells control HIV-1 infection, which may inform how to better engage these cells through vaccination
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