Background Caused by Mycobacterium tuberculosis, tuberculosis (TB) is an extremely contagious disease predominantly affecting the lungs. TB is found worldwide and has a major impact on public health safety primarily due to its high mortality rate. Applied for over a hundred years as a preventive measure, Mycobacterium bovis BCG remains the only available TB vaccine. Only one seminal study about the apoptotic pathways induced by this vaccine in the monocytic lineage of the host cell has found the effects of BCG on regulation of apoptosis. The aim of this study was to explore beyond that pioneer study the pathway related to the in vitro cell-death pattern and the inflammatory response to the BCG vaccine in human monocytes. Methods Cohorts of HIV-negative volunteers were enrolled: adult Healthy Donors (HD) and neonates' Umbilical Cord Blood (UCB) individuals. Host mononuclear cells were infected with the M. bovis Moreau strain of BCG vaccine at 16, 24, 48, and 72 h. The Real-Time RT-PCR for TRADD, Bcl-2, and Caspases-1 and -3 were performed, and supernatants were assayed in parallel for Caspase-1, NLRP3, HO-1, and IL-1β levels whereas caspases were assessed intracellularly. The effect of a BCG infection in monocytes was characterized via a metabolic activity assay by LDH release profiles. Results Overall, the BCG vaccine induced significantly higher Caspase-1 and Bcl-2 mRNA levels in both the HD and UCB groups (p-value ≤0.05). In addition, a significant increase solely in Caspase-1 protein levels was also noted in both HD and UCB (p-value ≤0.05) notwithstanding the absence of any damaged cell membranes. Conclusions Our data directly corroborate other findings showing that BCG Moreau led to an increased secretion of IL-1β but not IL-18, two Caspase-1-activated cytokines, and are also in support of the model that the BCG Moreau infection of human mononuclear cells may induce a cell-death pattern involving Caspase-1 activation.

中文翻译：

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诱导 Caspase-1 表达、释放和依赖性细胞死亡的人单核细胞的体外牛分枝杆菌 BCG Moreau 感染主要依赖于细胞完整性。

背景 由结核分枝杆菌引起的结核病 (TB) 是一种传染性极强的疾病，主要影响肺部。结核病在世界范围内都有发现，主要由于其高死亡率而对公共卫生安全产生重大影响。作为预防措施应用了一百多年，牛分枝杆菌 BCG 仍然是唯一可用的结核病疫苗。只有一项关于这种疫苗在宿主细胞单核细胞谱系中诱导的细胞凋亡途径的开创性研究发现了卡介苗对细胞凋亡的调节作用。本研究的目的是探索与体外细胞死亡模式和人类单核细胞中对卡介苗疫苗的炎症反应相关的途径。方法 招募 HIV 阴性志愿者队列：成人健康供体 (HD) 和新生儿 脐带血 (UCB) 个体。在 16、24、48 和 72 小时用 BCG 疫苗的 M. bovis Moreau 株感染宿主单核细胞。对 TRADD、Bcl-2 和 Caspase-1 和 -3 进行实时 RT-PCR，并平行测定上清液的 Caspase-1、NLRP3、HO-1 和 IL-1β 水平，同时评估半胱天冬酶细胞内。BCG 感染对单核细胞的影响通过 LDH 释放曲线的代谢活性测定来表征。结果 总体而言，BCG 疫苗在 HD 和 UCB 组中均诱导显着更高的 Caspase-1 和 Bcl-2 mRNA 水平（p 值≤0.05）。此外，尽管没有任何受损的细胞膜，但在 HD 和 UCB 中也注意到仅 Caspase-1 蛋白水平的显着增加（p 值≤0.05）。