Chronic Alcohol Consumption Increases the Severity of Murine Influenza Virus Infections

Abstract

Respiratory infections with both seasonal as well as potential pandemic Influenza viruses represent a significant burden on human health. Furthermore, viruses such as Influenza are increasingly recognized as important etiologic agents in community acquired pneumonia. Within the United States alone ~12.9 million people are heavy drinkers and chronic abuse of alcohol is known to increase the risk and severity of community acquired pneumonia. Given the lack of knowledge regarding Influenza disease in this population, we determined the effects of chronic alcohol consumption on Influenza virus infection. Herein, we report that mice exposed to chronic ethanol have sharp increases in morbidity, mortality, and pulmonary virus titers relative to controls. These increases in influenza severity correspond with inhibited pulmonary influenza-specific CD8 T cell responses. Further, chronic ethanol consumption results in an enhanced pulmonary lesion severity, similar to that recently described for pandemic influenzas. Together, our results suggest that chronic alcohol consumption may increase the risk for severe influenza virus infections by altering the pulmonary inflammatory environment and CD8 T cell response.

Exploiting cross-priming to generate protective CD8 T-cell immunity rapidly

“…For influenza infection, BALB/c mice were anesthetized by isofluorane and were infected intranasally with a tissue culture infectious dose 50 (∼6.4-8 × 10 4 of virus) in 50 μL of Iscoves medium. Three days after infection, lungs were homogenized, and viral titers were determined as previously described (48).…”

Pulmonary cytokine composition differs in the setting of alcohol use disorders and cigarette smoking

“…Notably, in the most recent H1N1 epidemic, cigarette smoking increased the risk for hospitalization in the context of this illness (65), further adding to the clinical relevance of this association. Chronic exposure to alcohol in animal models enhances the severity of influenza infection (35) and has also been associated with the development of seasonal influenza, but not specifically H1N1 (47). Improved understanding of the relationship between smoking, AUDs, and influenza could be important given pneumonia that commonly occurs after primary influenza infections.…”

Chronic ethanol exposure selectively inhibits the influenza-specific CD8 T cell response during influenza A virus infection

“…While studies have begun to elucidate the mechanisms leading to this increased pulmonary disease severity in alcoholics, much remains unknown (Happel and Nelson, 2005, Legge and Waldschmidt, 2014, Meyerholz et al, 2008, Joshi and Guidot, 2007, Nelson et al, 1991, Zhang et al, 2002, Brown et al, 2004, Downs et al, 2013, Sisson, 2007, Bird and Kovacs, 2008. Therefore, it has been of continued interest to determine the effect of chronic alcohol consumption on the pulmonary adaptive immune response.…”