title: RSV-specific anti-viral immunity is disrupted by chronic ethanol consumption.
abstract: Alcohol-use disorders (AUD) persist in the United States and are heavily associated with an increased susceptibility to respiratory viral infections. Respiratory syncytial virus (RSV) in particular has received attention as a viral pathogen commonly detected in children and immune-compromised populations (elderly, asthmatics), yet more recently was recognized as an important viral pathogen in young adults. Our study evaluated the exacerbation of RSV-associated illness in mice that chronically consumed alcohol for 6 weeks prior to infection. Prior studies showed that lung viral titers remained elevated in these animals, leading to a hypothesis that T-cell activation and immune specificity were deficient in controlling viral spread and replication in the lungs. Herein, we confirm a reduction in RSV-specific IFNγ production by CD8 T cells and a depolarization of Th1 (CD4+IFNγ+) and Th2 (CD4+IL-4+) T cells at day 5 after RSV infection. Furthermore, over the course of viral infection (day 1 to day 7 after RSV infection), we detected a delayed influx of neutrophils, monocytes/macrophages, and lymphocytes into the lungs. Taken together, the data show that both the early and late adaptive immunity to RSV infection are altered by chronic ethanol consumption. Future studies will determine the interactions between the innate and adaptive immune systems to delineate therapeutic targets for individuals with AUD often hospitalized by respiratory infection.
authors: University of Nebraska Medical Center, Pulmonary, Critical Care, Sleep & Allergy Division, 985910 Nebraska Medical Center, Omaha, NE 68198-5910, USA.
authors: Kristi J
authors: KJ
authors: Warren
authors: University of Nebraska Medical Center, Pulmonary, Critical Care, Sleep & Allergy Division, 985910 Nebraska Medical Center, Omaha, NE 68198-5910, USA.
authors: Samantha M
authors: SM
authors: Simet
authors: University of Nebraska Medical Center, Pulmonary, Critical Care, Sleep & Allergy Division, 985910 Nebraska Medical Center, Omaha, NE 68198-5910, USA.
authors: Jacqueline A
authors: JA
authors: Pavlik
authors: University of Nebraska Medical Center, Pulmonary, Critical Care, Sleep & Allergy Division, 985910 Nebraska Medical Center, Omaha, NE 68198-5910, USA.
authors: Jane M
authors: JM
authors: DeVasure
authors: University of Nebraska Medical Center, Pulmonary, Critical Care, Sleep & Allergy Division, 985910 Nebraska Medical Center, Omaha, NE 68198-5910, USA.
authors: Joseph H
authors: JH
authors: Sisson
authors: University of Nebraska Medical Center, Pulmonary, Critical Care, Sleep & Allergy Division, 985910 Nebraska Medical Center, Omaha, NE 68198-5910, USA.
authors: Jill A
authors: JA
authors: Poole
authors: University of Nebraska Medical Center, Pulmonary, Critical Care, Sleep & Allergy Division, 985910 Nebraska Medical Center, Omaha, NE 68198-5910, USA; VA Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA; University of Nebraska Medical Center, Department of Environmental, Agricultural, & Occupational Health, 985910 Nebraska Medical Center, Omaha, NE 68198-5910, USA. Electronic address: twyatt@unmc.edu.
authors: Todd A
authors: TA
authors: Wyatt
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011897:Random Allocation; D012136:Respiratory Syncytial Viruses / Q000187:drug effects / Q000276:immunology*; D019562:Viral Load / Q000187:drug effects / Q000276:immunology
chemical_list: D000431:Ethanol