Altered anti-viral immune responses in monocytes in overweight heavy drinkers
iScience, 2023
Kim A., Ortega-Ribera M., McMullen M., Bellar A., Taiwo M., Pathak V., Streem D., Dasarathy J., Welch N., Dasarathy S., Vachharajani V., Nagy L.
Disease area | Application area | Sample type | Products |
---|---|---|---|
Infectious Diseases | Pathophysiology | Plasma | Olink Explore 3072/384 |
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.