Chronic Alcohol Intake Compromises Lung Immunity by Altering Immunometabolism in Humans and Mouse Models

Area of Science:

• Immunology
• Toxicology
• Genomics

Background:

• Chronic alcohol consumption impairs lung immunity and host defense.
• Individuals with alcohol use disorder face increased susceptibility to severe inflammatory lung conditions.

Purpose of the Study:

• To investigate the molecular and cellular impacts of alcohol ingestion on lung immunity in males and females.
• To compare alcohol's effects on lung versus liver immunity.

Main Methods:

• Population-based human lung transcriptomics analysis.
• Experimental mouse model of chronic alcohol drinking (NIAAA model).
• Flow cytometry and comparative transcriptomics of lung and liver tissues.

Main Results:

• Chronic alcohol drinking exhibits sexually dimorphic effects on lung immunity in humans and mice, with male lungs being more sensitive.
• Lungs are more susceptible than the liver to alcohol-induced downregulation of immune genes and pathways.
• Alcohol consumption alters lung immunometabolism, downregulating immune and upregulating metabolic pathways, reducing mTOR signaling, and decreasing immune cell populations.

Conclusions:

• Sex-specific differences exist in alcohol's impact on lung immunity.
• Immunometabolic alterations are central to alcohol-induced lung damage.
• mTOR signaling may be a key upstream regulator of alcohol-induced lung immune dysregulation.