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Effects of binge alcohol exposure on Burkholderia thailandensis-alveolar macrophage interaction
Victor Jimenez1, Ryan Moreno1, Emily Kaufman2
1Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ, USA.
Abstract:
Alcohol consumption has diverse and well-documented effects on the human immune system and its ability to defend against infective agents. One example is melioidosis, a disease caused by infection with Burkholderia pseudomallei, which is of public health importance in Southeast Asia and Northern Australia, with an expanding global distribution. While B. pseudomallei infections can occur in healthy humans, binge alcohol use is progressively being recognized as a major risk factor. Although binge alcohol consumption has been considered as a risk factor for the development of melioidosis, no experimental studies have investigated the outcomes of alcohol exposure on Burkholderia spp. infection. Therefore, we proposed the use of non-pathogenic B. thailandensis E264 as a useful BSL-1 model system to study the effects of binge alcohol exposure on bacteria and alveolar macrophage interactions. The MH-S alveolar macrophage (AMs) cell line was used to characterize innate immune responses to infection in vitro. Our results showed that alcohol exposure significantly suppressed the uptake and killing of B. thailandensis by AMs. Alveolar macrophages incubated in alcohol (0.08%) for 3 h prior to infection showed significantly lower bacterial uptake at 2 and 8 h post infection. Activated AMs with IFN-γ and pre and post-incubation in alcohol when exposed to B. thailandensis released lower nitric oxide (NO) concentrations, compared to activated AMs with IFN-γ from non-alcoholic controls. As a result, B. thailandensis survival and replication increased ∼2.5-fold compared to controls. The presence of alcohol (1%) also increased bacterial survival within AMs. Alcohol significantly decreased bacterial motility compared to non-alcoholic controls. Increased biofilm formation was observed at 3 and 6 h when bacteria were pre-incubated in (0.08%) alcohol. These results provide insights into binge alcohol consumption, a culturally prevalent risk factor, as a predisposing factor for melioidosis.
Insights
Binge alcohol consumption impairs immune cells, increasing the risk of melioidosis. This study shows alcohol suppresses alveolar macrophage function, boosting Burkholderia thailandensis survival and biofilm formation, highlighting alcohol as a melioidosis risk factor.
Area of Science:
- Immunology
- Microbiology
- Toxicology
Background:
- Alcohol consumption impacts immune defenses against infections.
- Melioidosis, caused by Burkholderia pseudomallei, is a significant public health concern in endemic regions.
- Binge alcohol use is increasingly recognized as a risk factor for melioidosis, yet experimental data is lacking.
Purpose of the Study:
- To investigate the effects of binge alcohol exposure on host-pathogen interactions using a model system.
- To characterize the impact of alcohol on alveolar macrophage (AMs) innate immune responses to Burkholderia thailandensis.
- To understand how alcohol influences bacterial survival, replication, motility, and biofilm formation.
Main Methods:
- Utilized a non-pathogenic B. thailandensis E264 strain in a Biosafety Level 1 (BSL-1) model.
- Employed the MH-S alveolar macrophage cell line for in vitro studies.
- Assessed bacterial uptake, killing, nitric oxide (NO) production, bacterial survival, motility, and biofilm formation under varying alcohol concentrations and incubation times.
Main Results:
- Alcohol exposure significantly suppressed AMs' uptake and killing of B. thailandensis.
- Activated AMs exposed to alcohol produced lower nitric oxide (NO) levels, leading to increased bacterial survival and replication (~2.5-fold).
- Alcohol decreased bacterial motility and increased biofilm formation, particularly at higher concentrations and longer pre-incubation periods.
Conclusions:
- Binge alcohol consumption impairs critical innate immune functions of alveolar macrophages.
- Alcohol exposure promotes increased survival, replication, and altered behavior of Burkholderia species.
- These findings provide experimental evidence supporting binge alcohol use as a predisposing factor for melioidosis.
