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
Affiliations
Adam Kim
Northern Ohio Alcohol Center, Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH, USA; Department of Medicine, University of Connecticut Health Center, Farmington, CT, USA; Corresponding author
Martí Ortega-Ribera
Northern Ohio Alcohol Center, Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH, USA
Megan R. McMullen
Northern Ohio Alcohol Center, Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH, USA
Annette Bellar
Northern Ohio Alcohol Center, Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH, USA
Moyinoluwa Taiwo
Northern Ohio Alcohol Center, Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH, USA
Vai Pathak
Northern Ohio Alcohol Center, Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH, USA
David Streem
Lutheran Hospital, Cleveland Clinic, Cleveland, OH, USA
Jaividhya Dasarathy
Department of Family Medicine, MetroHealth, Cleveland, OH, USA
Nicole Welch
Northern Ohio Alcohol Center, Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH, USA; Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA; Department of Molecular Medicine, Case Western Reserve University, Cleveland, OH, USA
Srinivasan Dasarathy
Northern Ohio Alcohol Center, Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH, USA; Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA; Department of Molecular Medicine, Case Western Reserve University, Cleveland, OH, USA
Vidula Vachharajani
Northern Ohio Alcohol Center, Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH, USA; Department of Critical Care Medicine Cleveland Clinic Respiratory Institute, Cleveland, OH, USA
Laura E. Nagy
Northern Ohio Alcohol Center, Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH, USA; Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA; Department of Molecular Medicine, Case Western Reserve University, Cleveland, OH, USA
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.
