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Chronic Ethanol Exposure Selectively Inhibits the Influenza‐Specific CD 8 T Cell Response During Influenza A Virus Infection
Author(s) -
Hemann Emily A.,
McGill Jodi L.,
Legge Kevin L.
Publication year - 2014
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12522
Subject(s) - influenza a virus , immunology , t cell , cd8 , cytokine , tumor necrosis factor alpha , cytotoxic t cell , lesion , virus , biology , immune system , interferon , medicine , pathology , in vitro , biochemistry
Background It is well established that chronic ethanol (Et OH ) 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 CD 8 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 CD 8 T cell compartment during chronic Et OH consumption remains unknown. Methods Utilizing the Meadows–Cook murine model of chronic alcohol consumption, mice received Et OH in their drinking water for 8 or 12 weeks. Mice were challenged intranasally with IAV , and the activation and effector functions of IAV ‐specific CD 8 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 d LN of IAV‐infected, EtOH‐consuming mice. Conclusions These findings highlight the previously unrecognized depth of the lesion in the IAV ‐specific CD 8 T cell response during chronic Et OH consumption. Given the important role CD 8 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 CD 8 T cell response and reduce serious disease outcomes associated with IAV infections in alcoholics.