Single cell transcriptomics reveals opioid usage evokes widespread suppression of antiviral gene program

• Published in: Nature communications 2020-05, Vol.11 (1), p.2611-10, Article 2611
• Main Authors: Karagiannis, Tanya T., Cleary, John P., Gok, Busra, Henderson, Andrew J., Martin, Nicholas G., Yajima, Masanao, Nelson, Elliot C., Cheng, Christine S.
• Format: Article
• Language: English
• Subjects: 38; 38/91; 631/250/2499; 631/250/2502; 631/337/2019; 631/553; Addictions; Adult; Antiviral Agents - pharmacology; Blood cells; Central nervous system; Drug abuse; Female; Gene Expression Profiling; Gene Expression Regulation - drug effects; Gene Expression Regulation - immunology; Gene sequencing; Humanities and Social Sciences; Humans; Immune response; Immune system; Immunity, Innate - genetics; Interferons - pharmacology; Leukocytes, Mononuclear; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Male; Middle Aged; Monocytes; Morphine; Morphine - pharmacology; multidisciplinary; Narcotics; Opioid-Related Disorders - immunology; Opioids; Peripheral blood mononuclear cells; Ribonucleic acid; RNA; Science; Science (multidisciplinary); Single-Cell Analysis; Virus Diseases - immunology; Young Adult
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-16159-y

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. Over 100 million of opioid prescriptions are issued yearly in the USA alone, but the impact of opioid use on the immune system is barely characterized. Here the authors report antiviral immune response is blunted in several types of blood cells from opioid-dependent individuals, and when healthy donor cells are exposed to morphine in a dish.