Thesis
The detrimental effects of chronic alcohol consumption on the immune response during murine cytomegalovirus infection
Washington State University
Master of Science (MS), Washington State University
05/2018
DOI:
https://doi.org/10.7273/000004022
Handle:
https://hdl.handle.net/2376/124717
Abstract
Alcoholism and alcohol abuse are global problems that were a factor in over 5% of deaths worldwide in 2014. Alcohol consumption has been implicated as a factor in exacerbating communicable diseases by suppressing the immune system and allowing infection or permitting persistent infections to reemerge. Major findings in both epidemiological studies and animal models have demonstrated that alcohol consumption suppresses the immune system, specifically natural killer cells and cytotoxic CD8+ T cells, by reducing cell numbers and their cytotoxicity. Cytomegalovirus (CMV) is a member of the herpesvirus family and infection is very common in humans. Immunocompetent individuals are asymptomatic in due to the immune system's ability to control the infection effectively. However, CMV infection can cause life-threatening complications in immunocompromised individuals such as alcoholics. It is well documented by clinical case reports that CMV infection exacerbates pneumonia, HCV and HIV infection, and life-threatening liver decompensation in human alcoholics, but the progression of CMV infection in alcoholics is poorly understood. Using a chronic alcohol consumption (CAC) mouse model and murine CMV (mCMV) we characterized the progression of acute mCMV infection and how alcohol disrupted the antiviral response. We found that CAC increased the viral load in spleen 4 days post infection, enhanced body weight loss, and inhibited splenomegaly during the acute infection. 12 hours post infection cellular IFN-[beta] and the percentage of IFN-[gamma]-producing NK cells in the spleen were significantly lower in alcohol-consuming mice. Alcohol consumption decreased IL-15-producing dendritic cells in the spleen and liver 36 hours post infection and inhibited NK cell maturation and Ly49H+ NK cell expansion in spleen and liver 3 to 6 days post-infection. Alcohol consumption enhanced NK cell and CD8+ T cell activation, observed as continuous upregulation of CD69 and granzyme B expression in NK and CD8+ T cells in spleen and liver during acute mCMV infection. These results indicate that CAC, by impairing non-specific NK cell and Ly49H+ NK cell activation, exacerbates mCMV infection and compromises viral clearance, which in turn enhances NK cell and CD8+ T cell continuous activation and inflammation resulting in impaired viral clearance, enhanced body weight loss and severe organ damage.
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Details
- Title
- The detrimental effects of chronic alcohol consumption on the immune response during murine cytomegalovirus infection
- Creators
- Alexander Armstrong Little
- Contributors
- Hui H Zhang (Chair) - Washington State University, Department of Pharmaceutical SciencesGary G Meadows (Committee Member) - Washington State University, Department of Pharmaceutical SciencesKathryn Meier (Committee Member) - Washington State University, Department of Pharmaceutical SciencesPhilip Fowler Mixter (Committee Member) - Washington State University, School of Molecular Biosciences
- Awarding Institution
- Washington State University
- Academic Unit
- Department of Pharmaceutical Sciences
- Theses and Dissertations
- Master of Science (MS), Washington State University
- Publisher
- Washington State University
- Number of pages
- 101
- Identifiers
- 99900890795801842
- Language
- English
- Resource Type
- Thesis