Pulmonary/Critical Care Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
Alcohol Clin Exp Res. 2012 Feb;36(2):310-7. doi: 10.1111/j.1530-0277.2011.01624.x. Epub 2011 Oct 20.
Alcoholics are at heightened risk for developing active tuberculosis. This study evaluates chronic alcohol consumption in a murine model of vaccination with Mycobacterium bovis Bacille Calmette-Guèrin (BCG) and subsequent pulmonary infection with virulent Mycobacterium tuberculosis.
BALB/c mice were administered the Lieber-DeCarli liquid ethanol diet or pair-fed the liquid control diet for 3 weeks either before or after subcutaneous vaccination with M. bovis BCG. At least 3 weeks after BCG vaccination, groups of mice on the aforesaid diets were challenged with intratracheal infection with M. tuberculosis H37Rv. Lung mycobacterial burden, and lung and lung-associated lymph node CD4(+) lymphocyte production of tuberculosis-specific interferon (IFN)-γ were assayed. Popliteal lymph node lymphocytes from both dietary regimens undergoing BCG vaccination (in the absence of M. tuberculosis infection) were also evaluated for purified protein derivative-induced IFN-γ production by ELISpot assay.
Mice begun on alcohol prior to vaccination with M. bovis BCG demonstrated impaired control of pulmonary challenge with virulent M. tuberculosis, as well as impaired lung CD4(+) and popliteal lymph node T-cell IFN-γ responses. If BCG vaccination was delivered prior to initiation of alcohol feeding, the mice remained protected against a subsequent challenge with M. tuberculosis, and BCG-induced immunity was not impaired in either the lung or the popliteal lymph nodes.
Alcohol consumption blunts the development of the adaptive immune response to M. bovis BCG vaccination, which impairs the control of a secondary challenge with M. tuberculosis, but only if the alcohol exposure is begun prior to BCG vaccination. These results provide insight into mechanisms by which alcohol consumption impairs antimycobacterial immunity, including in response to vaccination and subsequent pathogenic challenge.
酗酒者发生活动性肺结核的风险增加。本研究评估了在牛型分枝杆菌卡介苗（BCG）接种的小鼠模型中慢性酒精消耗，并随后用有毒结核分枝杆菌进行肺部感染。
BALB/c 小鼠在皮下接种牛型分枝杆菌 BCG 之前或之后，用 Lieber-DeCarli 液体乙醇饮食或配对喂养液体对照饮食喂养 3 周。在 BCG 接种后至少 3 周，用上述饮食的各组小鼠经气管内感染结核分枝杆菌 H37Rv 进行挑战。测定肺分枝杆菌负荷和肺及肺相关淋巴结 CD4(+)淋巴细胞产生结核特异性干扰素（IFN）-γ。还通过 ELISpot 测定评估来自两种饮食方案的接种 BCG 的（在没有结核分枝杆菌感染的情况下）的鼠后脚淋巴结淋巴细胞对纯化蛋白衍生物诱导的 IFN-γ产生。
在接种牛型分枝杆菌 BCG 之前开始饮酒的小鼠对有毒结核分枝杆菌肺部挑战的控制能力受损，肺 CD4(+)和鼠后脚淋巴结 T 细胞 IFN-γ 反应受损。如果在开始饮酒之前给予 BCG 接种，则小鼠仍能免受随后结核分枝杆菌的挑战，并且无论是在肺部还是在鼠后脚淋巴结中，BCG 诱导的免疫均未受损。
酒精消耗削弱了对牛型分枝杆菌 BCG 接种的适应性免疫反应的发展，这削弱了对结核分枝杆菌的二次挑战的控制，但前提是酒精暴露发生在 BCG 接种之前。这些结果提供了对酒精消耗如何损害抗分枝杆菌免疫的机制的见解，包括对疫苗接种和随后的致病挑战的反应。
