1. Altered anti-viral immune responses in monocytes in overweight heavy drinkers
- Author
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Adam Kim, Martí Ortega-Ribera, Megan R. McMullen, Annette Bellar, Moyinoluwa Taiwo, Vai Pathak, David Streem, Jaividhya Dasarathy, Nicole Welch, Srinivasan Dasarathy, Vidula Vachharajani, and Laura E. Nagy
- Subjects
Molecular biology ,Immunology ,Omics ,Transcriptomics ,Science - Abstract
Summary: 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.
- Published
- 2023
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