학술논문
Chronic alcohol consumption dysregulates innate immune response to SARS-CoV-2 in the lung.
Document Type
Academic Journal
Author
Lewis SA; Department of Molecular Biology and Biochemistry, School of Biological Sciences, University of California Irvine, USA.; Cinco IR; Microbiology, Immunology and Molecular Genetics, College of Medicine, University of Kentucky, USA.; Doratt BM; Microbiology, Immunology and Molecular Genetics, College of Medicine, University of Kentucky, USA.; Blanton MB; Microbiology, Immunology and Molecular Genetics, College of Medicine, University of Kentucky, USA; Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, USA.; Hoagland C; Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, USA.; Newman N; Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, USA.; Davies M; Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, USA.; Grant KA; Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, USA.; Messaoudi I; Microbiology, Immunology and Molecular Genetics, College of Medicine, University of Kentucky, USA. Electronic address: ilhem.messaoudi@uky.edu.
Source
Publisher: Elsevier B.V Country of Publication: Netherlands NLM ID: 101647039 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2352-3964 (Electronic) Linking ISSN: 23523964 NLM ISO Abbreviation: EBioMedicine Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Alcohol consumption is widespread with over half of the individuals over 18 years of age in the U.S. reporting alcohol use in the last 30 days. Moreover, 9 million Americans engaged in binge or chronic heavy drinking (CHD) in 2019. CHD negatively impacts pathogen clearance and tissue repair, including in the respiratory tract, thereby increasing susceptibility to infection. Although, it has been hypothesized that chronic alcohol consumption negatively impacts COVID-19 outcomes; the interplay between chronic alcohol use and SARS-CoV-2 infection outcomes has yet to be elucidated.
Methods: In this study we employed luminex, scRNA sequencing, and flow cytometry to investigate the impact of chronic alcohol consumption on SARS-CoV-2 anti-viral responses in bronchoalveolar lavage cell samples from humans with alcohol use disorder and rhesus macaques that engaged in chronic drinking.
Findings: Our data show that in both humans (n = 6) and macaques (n = 11), the induction of key antiviral cytokines and growth factors was decreased with chronic ethanol consumption. Moreover, in macaques fewer differentially expressed genes mapped to Gene Ontology terms associated with antiviral immunity following 6 month of ethanol consumption while TLR signaling pathways were upregulated.
Interpretation: These data are indicative of aberrant inflammation and reduced antiviral responses in the lung with chronic alcohol drinking.
Funding: This study was supported by NIH 1R01AA028735-04 (Messaoudi), U01AA013510-20 (Grant), R24AA019431-14 (Grant), R24AA019661 (Burnham), P-51OD011092 (ONPRC core grant support). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Competing Interests: Declaration of interests There are no competing interests to report.
(Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
Methods: In this study we employed luminex, scRNA sequencing, and flow cytometry to investigate the impact of chronic alcohol consumption on SARS-CoV-2 anti-viral responses in bronchoalveolar lavage cell samples from humans with alcohol use disorder and rhesus macaques that engaged in chronic drinking.
Findings: Our data show that in both humans (n = 6) and macaques (n = 11), the induction of key antiviral cytokines and growth factors was decreased with chronic ethanol consumption. Moreover, in macaques fewer differentially expressed genes mapped to Gene Ontology terms associated with antiviral immunity following 6 month of ethanol consumption while TLR signaling pathways were upregulated.
Interpretation: These data are indicative of aberrant inflammation and reduced antiviral responses in the lung with chronic alcohol drinking.
Funding: This study was supported by NIH 1R01AA028735-04 (Messaoudi), U01AA013510-20 (Grant), R24AA019431-14 (Grant), R24AA019661 (Burnham), P-51OD011092 (ONPRC core grant support). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Competing Interests: Declaration of interests There are no competing interests to report.
(Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)