Single cell transcriptomics reveals opioid usage evokes widespread suppression of antiviral gene program
Tanya T Karagiannis1,2, John P Cleary2,3, Busra Gok2,4
1Program in Bioinformatics, Boston University, 24 Cummington Mall, Boston, MA, 02215, USA.
Abstract:
Chronic opioid usage not only causes addiction behavior through the central nervous system, but also modulates the peripheral immune system. However, how opioid impacts the immune system is still barely characterized systematically. In order to understand the immune modulatory effect of opioids in an unbiased way, here we perform single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells from opioid-dependent individuals and controls to show that chronic opioid usage evokes widespread suppression of antiviral gene program in naive monocytes, as well as in multiple immune cell types upon stimulation with the pathogen component lipopolysaccharide. Furthermore, scRNA-seq reveals the same phenomenon after a short in vitro morphine treatment. These findings indicate that both acute and chronic opioid exposure may be harmful to our immune system by suppressing the antiviral gene program. Our results suggest that further characterization of the immune modulatory effects of opioid is critical to ensure the safety of clinical opioids.
Insights
Chronic opioid use suppresses the immune system by inhibiting antiviral gene programs in monocytes and other immune cells. This effect occurs with both long-term use and short-term morphine exposure, impacting immune defenses.
Area of Science:
- Immunology
- Neuroscience
- Pharmacology
Background:
- Opioid addiction affects the central nervous system.
- Opioid use also impacts the peripheral immune system.
- Systematic characterization of opioid's immune modulation is lacking.
Purpose of the Study:
- To unbiasedly characterize the immune modulatory effects of chronic opioid usage.
- To investigate the impact of acute opioid exposure on immune cell function.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) was performed on peripheral blood mononuclear cells.
- Samples were analyzed from individuals with opioid dependence and healthy controls.
- Immune cell responses were assessed after lipopolysaccharide stimulation and in vitro morphine treatment.
Main Results:
- Chronic opioid use suppressed antiviral gene programs in naive monocytes.
- Suppression of antiviral gene programs was observed in multiple immune cell types post-lipopolysaccharide stimulation.
- In vitro morphine treatment also led to the suppression of antiviral gene programs.
Conclusions:
- Both acute and chronic opioid exposure can harm the immune system by suppressing antiviral responses.
- Further research into opioid's immune modulatory effects is crucial for clinical safety.
- Opioid-induced immune suppression may compromise the body's ability to fight infections.
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