Year: 2023
Type: article
Abstract: Alcohol abuse causes increased susceptibility to respiratory syndromes like bacterial pneumonia and viral infections like SARS-CoV-2. Heavy drinkers (HD) are at higher risk of severe COVID-19 if they are also overweight, yet the molecular mechanisms are unexplored. Single-cell RNA-sequencing (scRNA-seq) was performed on peripheral blood mononuclear cells from lean or overweight HD and healthy controls (HC) after challenge with a dsRNA homopolymer (PolyI:C) to mimic a viral infection and/or with lipopolysaccharide (LPS). All monocyte populations responded to both PolyI:C and LPS with pro-inflammatory gene expression. However, the expression of interferon-stimulated genes, essential for inhibiting viral pathogenesis, was greatly reduced in overweight patients. Interestingly, the number of upregulated genes in response to the PolyI:C challenge was far greater in monocytes from HD compared to HC, including much stronger pro-inflammatory cytokine and interferon-γ signaling responses. These results suggest that increased body weight reduced anti-viral responses while heavy drinking increased pro-inflammatory cytokines.
Source: iScience
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,150
Funders: Cleveland Clinic, American College of Gastroenterology, Societat Catalana de Digestologia, National Institutes of Health, Instituto de Salud Carlos III, National Institute on Alcohol Abuse and Alcoholism, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Awards: Novel therapeutics for alcoholic hepatitis - Cleveland Translational Component, Hyperammonemia reduces skeletal muscle protein synthesis via a beta-catenin-cMyc mediated impaired ribosomal biogenesis, G2260595526, C-Type Lectins and Immune Surveillance in ALD, G2713162615, Sarcopenia in cirrhosis is mediated by a hyperammonemic stress response, G4493526636, Immersive Training in Glycosciences, G6965305005, Mechanisms of Malnutrition in Cirrhosis with Portosystemic Shunting, G7121403099, Nutritional modulation to minimize resistance exercise induced metabolic deregulations and improve training responsiveness in Chronic Obstructive Pulmonary Disease, Alcoholic Hepatitis Consortia: an intramural/extramural collaboration to unravel genetic determinants, IRAKM and Mincle in ALD, VCU-Atlanta Center for the Childhood Liver Disease Research Network (ChiLDReN), Alcohol and tissue injury, from mechanisms to treatments, Immuno-metabolic dysfunction in alcohol with sepsis, Continuation of the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Clinical Center-Cleveland site, Integrated Therapies for Alcohol use in Alcohol-associated Liver Disease (ITAALD)- Cleveland Clinic Clinical Center, Transcriptional and non-transcriptional function of IRF3 in ALD
OpenAlex ID: W4380989215