Abstract
BACKGROUND: It is well established that chronic ethanol (EtOH) consumption is associated with increased incidence and disease severity of respiratory infections. Our recent work demonstrates this increase in disease severity to influenza A virus (IAV) infections is due, in part, to a failure to mount a robust IAV-specific CD8 T cell response along with a specific impairment in the ability of these T cells to produce interferon γ (IFNγ). However, the full extent of the lesion in the effector CD8 T cell compartment during chronic EtOH consumption remains unknown. METHODS: Utilizing the Meadows-Cook murine model of chronic alcohol consumption, mice received EtOH in their drinking water for 8 or 12 weeks. Mice were challenged intranasally with IAV, and the activation and effector functions of IAV-specific CD8 T cells were determined in both the lung-draining lymph nodes (dLN) and lungs. RESULTS: Our results confirm the defect in IFNγ production; however, the ability of IAV-specific T cells to produce tumor necrosis factor α (TNFα) and interleukin-2 (IL-2) in EtOH-consuming mice remains unaltered. In contrast, EtOH consumption significantly reduces the ability of CD8 T cells to degranulate and kill IAV-specific targets. Finally, our findings suggest the lesion begins during the initial activation of CD8 T cells, as we observe early defects in proliferation in the dLN of IAV-infected, EtOH-consuming mice. CONCLUSIONS: These findings highlight the previously unrecognized depth of the lesion in the IAV-specific CD8 T cell response during chronic EtOH consumption. Given the important role CD8 T cell immunity plays in control of IAV, these findings may aid in the development of vaccination and/or therapeutic strategies to reverse these defects in the CD8 T cell response and reduce serious disease outcomes associated with IAV infections in alcoholics.