Jimenez Victor, Moreno Ryan, Kaufman Emily, Hornstra Heidie, Settles Erik, Currie Bart J, Keim Paul, Monroy Fernando P
Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ, USA.
Pathogen & Microbiome Institute (PMI), Northern Arizona University, Flagstaff, AZ, USA.
Alcohol. 2017 Nov;64:55-63. doi: 10.1016/j.alcohol.2017.04.004. Epub 2017 Aug 19.
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.
饮酒对人体免疫系统及其抵御感染因子的能力具有多种且有充分记录的影响。一个例子是类鼻疽，它是由伯克霍尔德菌感染引起的疾病，在东南亚和澳大利亚北部具有公共卫生重要性，且全球分布正在扩大。虽然健康人也可能感染伯克霍尔德菌，但酗酒正逐渐被视为一个主要风险因素。尽管酗酒被认为是类鼻疽发病的一个风险因素，但尚无实验研究探讨酒精暴露对伯克霍尔德菌属感染的影响。因此，我们提议使用非致病性的泰国伯克霍尔德菌E264作为一个有用的生物安全水平1级模型系统，来研究酗酒暴露对细菌与肺泡巨噬细胞相互作用的影响。MH-S肺泡巨噬细胞（AMs）细胞系用于体外表征对感染的固有免疫反应。我们的结果表明，酒精暴露显著抑制了AMs对泰国伯克霍尔德菌的摄取和杀伤。在感染前于酒精（0.08%）中孵育3小时的肺泡巨噬细胞在感染后2小时和8小时显示出显著更低的细菌摄取量。与来自无酒精对照组经γ干扰素激活的AMs相比，经γ干扰素激活且在酒精中预孵育和后孵育的AMs在暴露于泰国伯克霍尔德菌时释放出更低浓度的一氧化氮（NO）。结果，与对照组相比，泰国伯克霍尔德菌的存活和复制增加了约2.5倍。酒精（1%）的存在也增加了AMs内细菌的存活。与无酒精对照组相比，酒精显著降低了细菌的运动性。当细菌在（0.08%）酒精中预孵育时，在3小时和6小时观察到生物膜形成增加。这些结果为酗酒这一文化上普遍存在的风险因素作为类鼻疽的一个易感因素提供了见解。
