Chronic ethanol consumption causes lesions in CD8 T cell memory and is associated with increased susceptibility to influenza A virus infections

Abstract

Abstract Chronic alcohol consumption is associated with increased risk of severe disease during both bacterial and viral infections. We have previously shown that this increased disease severity during a primary influenza A virus (IAV) infection is due to deficits in the developing IAV-specific CD8 T cell response. Recent studies have highlighted that human alcoholics have increased susceptibility to IAV infections, even though they likely possess pre-existing immune memory to IAV. However, the effects of chronic alcohol consumption on pre-existing immune memory responses have not been explored. Here, our results show that mice previously exposed to IAV infection that then consumed alcohol (IAV-immune➞EtOH) exhibited increased morbidity and mortality to secondary heterologous IAV challenge compared to IAV-immune mice that had consumed water (IAV-immune➞H2O). This increased susceptibility in IAV-immune➞EtOH mice was associated with reduced IAV-specific killing of target cells. Furthermore, we observed a universal numerical reduction of all memory CD8 T cell subsets within the lungs of IAV-immune➞EtOH mice compared to IAV-immune➞H2O mice. Finally, our results show that IAV-specific CD8 T cell recall responses upon secondary IAV challenge are altered in IAV-immune➞EtOH mice, particularly within the lung tissue, and were associated with reduced expression of CXCL10 and CXCL11, suggesting defects in cell trafficking. Overall, these data demonstrate that the negative impacts of chronic alcohol consumption occur across the full CD8 T cell compartment, including both the naïve and memory response, contributing to lesions in the development of de novo CD8 T cell and pre-existing memory CD8 T cell responses.