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A mouse model of binge alcohol consumption and Burkholderia infection
Victor Jimenez1,2, Ryan Moreno1, Erik Settles1,2
1Department of Biological Sciences, Northern Arizona University, Flagstaff, Arizona, United States of America.
Background:
Binge drinking, an increasingly common form of alcohol consumption, is associated with increased mortality and morbidity; yet, its effects on the immune system's ability to defend against infectious agents are poorly understood. Burkholderia pseudomallei, the causative agent of melioidosis can occur in healthy humans, yet binge alcohol use is progressively being recognized as a major risk factor. Although our previous studies demonstrated that binge alcohol exposure results in reduced alveolar macrophage function and increased Burkholderia virulence in vitro, no experimental studies have investigated the outcomes of binge alcohol on Burkholderia spp. infection in vivo.
Principal Findings:
In this study, we used the close genetic relatives of B. pseudomallei, B. thailandensis E264 and B. vietnamiensis, as useful BSL-2 model systems. Eight-week-old female C57BL/6 mice were administered alcohol comparable to human binge drinking episodes (4.4 g/kg) or PBS intraperitoneally 30 min before a non-lethal intranasal infection. In an initial B. thailandensis infection (3 x 105), bacteria accumulated in the lungs and disseminated to the spleen in alcohol administered mice only, compared with PBS treated mice at 24 h PI. The greatest bacterial load occurred with B. vietnamiensis (1 x 106) in lungs, spleen, and brain tissue by 72 h PI. Pulmonary cytokine expression (TNF-α, GM-CSF) decreased, while splenic cytokine (IL-10) increased in binge drunk mice. Increased lung and brain permeability was observed as early as 2 h post alcohol administration in vivo. Trans-epithelial electrical resistance (TEER) was significantly decreased, while intracellular invasion of non-phagocytic cells increased with 0.2% v/v alcohol exposure in vitro.
Conclusions:
Our results indicate that a single binge alcohol dose suppressed innate immune functions and increased the ability of less virulent Burkholderia strains to disseminate through increased barrier permeability and intracellular invasion of non-phagocytic cells.
Insights
Binge alcohol consumption impairs the immune system, increasing susceptibility to bacterial infections like melioidosis. This study shows alcohol disrupts immune defenses and aids bacterial spread in vivo.
Area of Science:
- Immunology
- Microbiology
- Toxicology
Background:
- Binge drinking is a common alcohol consumption pattern linked to health issues, but its impact on immune defense against pathogens is unclear.
- Burkholderia pseudomallei causes melioidosis, and binge alcohol use is a recognized risk factor.
- Previous in vitro studies showed binge alcohol exposure impairs macrophage function and enhances Burkholderia virulence.
Purpose of the Study:
- To investigate the in vivo effects of binge alcohol consumption on Burkholderia spp. infection.
- To use BSL-2 model systems (B. thailandensis and B. vietnamiensis) to study alcohol's impact on host defense.
Main Methods:
- Mice were administered alcohol (4.4 g/kg) or PBS before intranasal infection with B. thailandensis or B. vietnamiensis.
- Bacterial load in lungs, spleen, and brain was measured at 24 and 72 hours post-infection.
- Cytokine expression (TNF-α, GM-CSF, IL-10) and tissue permeability (lung, brain) were assessed. In vitro experiments evaluated alcohol's effect on cell permeability and invasion.
Main Results:
- Alcohol-treated mice showed increased bacterial dissemination to the spleen with B. thailandensis and higher bacterial loads in lungs, spleen, and brain with B. vietnamiensis.
- Pulmonary immune responses were suppressed (decreased TNF-α, GM-CSF), while splenic responses were altered (increased IL-10) in alcohol-exposed mice.
- Binge alcohol exposure increased lung and brain permeability in vivo and decreased epithelial resistance and increased intracellular invasion in vitro.
Conclusions:
- A single binge alcohol dose suppresses innate immune functions.
- Alcohol consumption increases susceptibility to Burkholderia spp. by enhancing barrier permeability and intracellular invasion.
- These findings highlight the detrimental effects of binge drinking on host defense against bacterial infections.
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