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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Ruminant Diseases and Immunology Research » Research » Publications at this Location » Publication #302874
Title: Chronic ethanol exposure selectively inhibits the influenza-specific CD8 T cell response during influenza A virus infection

Author
item HEMANN, EMILY - University Of Iowa
item McGill, Jodi
item LEGGE, KEVIN - University Of Iowa

Submitted to: Alcoholism: Clinical and Experimental
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/1/2014
Publication Date: 9/1/2014
Citation: Hemann, E.A., McGill, J.L., Legge, K.L. 2014. Chronic ethanol exposure selectively inhibits the influenza-specific CD8 T cell response during influenza A virus infection. Alcoholism: Clinical and Experimental. 38(9):2403-2413. DOI: 10.1111/acer.12522.

Interpretive Summary: Chronic alcohol abuse in humans is associated with increased incidence and severity of respiratory infections. In particular, alcoholics are at increased risk for infection by influenza virus. We have established a model of chronic alcohol consumption in the mouse that replicates many of the lesions associated with alcohol abuse in humans and have previously shown that mice that are chronically exposed to alcohol demonstrate increased susceptibility to influenza virus infection. T cells are one of the immune cell populations that are essential for the control and clearance of influenza virus infection in the mouse. We report here that the increased susceptibility to influenza virus infection in alcohol-exposed mice is due to defects in certain key immunologic functions of this T cell compartment. Given the important role that T cell immunity plays in the control of influenza virus infection, effective targeting to reverse these defects may aid in reducing the serious outcomes associated with influenza virus infection in alcoholics.

Technical Abstract: It is well established that chronic ethanol (EtOH) consumption is associated with increases in the incidence and disease severity of respiratory infections. Our recent work as demonstrated that this increase in disease severity to influenza virus infections is due, in part, to a failure to mount a robust IAV-specific CD8 T cell response as well as a specific impairment in the ability of these T cells to produce the anti-viral effector molecule IFN'. However the full extent of the lesion in the effector response within the CD8 T cell compartment during chronic EtOH consumption remains unknown. Therefore, we herein determined the extent of the lesion within the IAV-specific CD8 T cell response of mice chronically consuming EtOH for 12 weeks. Surprisingly, while our results confirm the defect in IFN' production by IAV-specific CD8 T cells in mice chronically consuming EtOH, the ability of these T cells to produce TNFa and IL-2 is unaltered. In contrast, we observed a significant reduction in the cytotoxic function of these T cells as EtOH significantly reduced the ability of the T cells to degranulate and kill IAV-specific targets. Finally, we determined if these lesions originate with the T cells during their initial activation in the lymph nodes or are instead programmed at the effector stage once arriving in the lungs. Our findings suggest that the lesion begins during the initial activation as we observed early defects in proliferation and IFN' production in the lymph nodes of influenza infected EtOH-consuming mice. Together, these findings highlight the previously unrecognized depth of the lesion in the IAV-specific CD8 T cell response during chronic EtOH. Given the important role CD8 T cell immunity plays in control of IAV, effective targeting to reverse these defects in IAV3 specific CD8 T cells may aid in decreasing the serious outcomes associated with IAV infection in alcoholics.