Altered anti-viral immune responses in monocytes in overweight heavy drinkers

Adam Kim; Martí Ortega-Ribera; Megan R McMullen; Annette Bellar; Moyinoluwa Taiwo; Vai Pathak; David Streem; Jaividhya Dasarathy; Nicole Welch; Srinivasan Dasarathy; Vidula Vachharajani; Laura E Nagy

doi:10.1016/j.isci.2023.107133

Altered anti-viral immune responses in monocytes in overweight heavy drinkers

iScience. 2023 Jul 21;26(7):107133. doi: 10.1016/j.isci.2023.107133. Epub 2023 Jun 15.

Authors

Adam Kim^{1

2}, Martí Ortega-Ribera¹, Megan R McMullen¹, Annette Bellar¹, Moyinoluwa Taiwo¹, Vai Pathak¹, David Streem³, Jaividhya Dasarathy⁴, Nicole Welch^{1

5

6}, Srinivasan Dasarathy^{1

5

6}, Vidula Vachharajani^{1

7}, Laura E Nagy^{1

5

6}

Affiliations

¹ Northern Ohio Alcohol Center, Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH, USA.
² Department of Medicine, University of Connecticut Health Center, Farmington, CT, USA.
³ Lutheran Hospital, Cleveland Clinic, Cleveland, OH, USA.
⁴ Department of Family Medicine, MetroHealth, Cleveland, OH, USA.
⁵ Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA.
⁶ Department of Molecular Medicine, Case Western Reserve University, Cleveland, OH, USA.
⁷ Department of Critical Care Medicine Cleveland Clinic Respiratory Institute, Cleveland, OH, USA.

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.

Keywords: Immunology; Molecular biology; Omics; Transcriptomics.

Abstract

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