Chronic Ethanol Consumption Reduces Existing CD8 T Cell Memory and Is Associated with Lesions in Protection against Secondary Influenza A Virus Infections.

ABSTRACT: Chronic alcohol consumption is associated with an increased incidence of disease severity during pulmonary infections. Our previous work in a mouse model of chronic alcohol consumption has detailed that the primary influenza A virus (IAV)-specific CD8 T cell response in mice that consumed ethanol (EtOH) had a reduced proliferative capacity as well as the ability to kill IAV target cells. Interestingly, recent studies have highlighted that human alcoholics have an increased susceptibility to IAV infections, even though they likely possess pre-existing immunity to IAV. However, the effects of chronic alcohol consumption on pre-existing immune responses (i.e., memory) to IAV have not been explored. Our results presented in this study show that IAV-immune mice that then chronically consumed alcohol (X31?EtOH) exhibited increased morbidity and mortality following IAV re-exposure compared with IAV-immune mice that had consumed water (X31?H2O). This increased susceptibility in X31?EtOH mice was associated with reduced IAV-specific killing of target cells and a reduction in the number of IAV-specific CD8 T cells within the lungs. Furthermore, upon IAV challenge, recruitment of the remaining memory IAV-specific CD8 T cells into the lungs is reduced in X31?EtOH mice. This altered recruitment is associated with a reduced pulmonary expression of CXCL10 and CXCL11, which are chemokines that are important for T cell recruitment to the lungs. Overall, these results demonstrate that chronic alcohol consumption negatively affects the resting memory CD8 T cell response and reduces the ability of memory T cells to be recruited to the site of infection upon subsequent exposures, therein contributing to an enhanced susceptibility to IAV infections.

SUBMITTER: Zacharias ZR 

PROVIDER: S-EPMC6904436 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature