Chronic ethanol consumption increases susceptibility to influenza A virus infections via alteration of memory CD8 T cell responses

Abstract Alcoholism is estimated to contribute to approximately 95,000 deaths within the United States per year making it the third leading preventable cause of death. These alcohol-related deaths are due, in part, to the increased risk of severe disease that human alcoholics have during bacterial and viral infections. Our laboratory has previously shown using a mouse model of chronic ethanol consumption that increased disease severity during a primary influenza A virus (IAV) infection is due to deficits in the developing IAV-specific CD8 T cell response. However, unlike mice, human alcoholics have likely been exposed to IAV prior to the onset of alcohol consumption. Therefore, we determined the effects of chronic alcohol consumption on pre-existing IAV immunity. Our results show that mice with established immunity to IAV that then chronically consumed alcohol (IAV-immune➞EtOH) exhibited increased morbidity and mortality to secondary heterologous IAV challenge compared to IAV-immune mice that then consumed water (IAV-immune➞H2O). IAV-immune➞EtOH mice also showed deficits in IAV-specific killing of target cells and a reduction in the number of IAV-specific CD8 T cells compared to IAV-immune ➞H2O mice. Finally, our results show that following a heterologous IAV challenge, the fold-increase of IAV-specific CD8 T cells within the lungs of IAV-immune➞EtOH was reduced compared to IAV-immune➞H2O mice. Interestingly, IAV-immune➞EtOH mice had reduced expression of CXCL10 and CXCL11 within their lungs, suggesting defects in cell trafficking. Overall, these data and our prior studies demonstrate that chronic alcohol consumption negatively impacts both the naïve and memory compartments of the CD8 T cell response to IAV infection.