Altered anti-viral immune responses in monocytes in overweight heavy drinkers
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-sequencin...
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| Materiálatiipa: | Artihkal |
| Giella: | English |
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Elsevier
2023-07-01
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| Ráidu: | iScience |
| Fáttát: | |
| Liŋkkat: | http://www.sciencedirect.com/science/article/pii/S2589004223012105 |
| _version_ | 1827895525474566144 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Adam Kim |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T22:23:05Z |
| format | Article |
| id | doaj.art-d98479cccd364976b87e0478ee4d52c3 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-12T22:23:05Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-d98479cccd364976b87e0478ee4d52c32023-07-23T04:55:40ZengElsevieriScience2589-00422023-07-01267107133Altered anti-viral immune responses in monocytes in overweight heavy drinkersAdam Kim0Martí Ortega-Ribera1Megan R. McMullen2Annette Bellar3Moyinoluwa Taiwo4Vai Pathak5David Streem6Jaividhya Dasarathy7Nicole Welch8Srinivasan Dasarathy9Vidula Vachharajani10Laura E. Nagy11Northern 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 authorNorthern Ohio Alcohol Center, Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH, USANorthern Ohio Alcohol Center, Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH, USANorthern Ohio Alcohol Center, Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH, USANorthern Ohio Alcohol Center, Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH, USANorthern Ohio Alcohol Center, Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH, USALutheran Hospital, Cleveland Clinic, Cleveland, OH, USADepartment of Family Medicine, MetroHealth, Cleveland, OH, USANorthern 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, USANorthern 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, USANorthern Ohio Alcohol Center, Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH, USA; Department of Critical Care Medicine Cleveland Clinic Respiratory Institute, Cleveland, OH, USANorthern 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, USASummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004223012105Molecular biologyImmunologyOmicsTranscriptomics |
| spellingShingle | 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 Altered anti-viral immune responses in monocytes in overweight heavy drinkers iScience Molecular biology Immunology Omics Transcriptomics |
| title | Altered anti-viral immune responses in monocytes in overweight heavy drinkers |
| title_full | Altered anti-viral immune responses in monocytes in overweight heavy drinkers |
| title_fullStr | Altered anti-viral immune responses in monocytes in overweight heavy drinkers |
| title_full_unstemmed | Altered anti-viral immune responses in monocytes in overweight heavy drinkers |
| title_short | Altered anti-viral immune responses in monocytes in overweight heavy drinkers |
| title_sort | altered anti viral immune responses in monocytes in overweight heavy drinkers |
| topic | Molecular biology Immunology Omics Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223012105 |
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