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首页> 外文期刊>Biology Open >Enhanced survival of BCG-stimulated dendritic cells: involvement of anti-apoptotic proteins and NF-κB
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Enhanced survival of BCG-stimulated dendritic cells: involvement of anti-apoptotic proteins and NF-κB

机译：BCG刺激的树突状细胞的存活率提高：抗凋亡蛋白和NF-κB的参与

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BCG (Bacillus Calmette-Guérin) is the only available vaccine against TB and is also used for the treatment of superficial bladder cancer. BCG-mediated protection against TB and bladder cancer has been shown to rely on its ability to induce superior CD4+and CD8+T cell responses. As the magnitude of T cell responses is defined by dendritic cell (DC) lifespan, we examined the effect of BCG on DC survival and its underlying mechanisms. It was observed that BCG stimulation enhanced DC survival and prolonged DC lifespan in a dose-dependent manner. Live BCG led to a higher DC survival compared with heat-killed BCG. FITC-Annexin V staining showed that BCG promoted DC survival by inhibiting apoptosis. Consistently, higher expressions of anti-apoptotic proteins Bcl-2 and Bcl-xLwere observed in BCG-stimulated DCs. Pharmacological inhibition of Bcl-2 and Bcl-xLdrastically reduced the DC survival efficacy of BCG. Comparable survival of BCG-stimulated wild-type and MyD88?/?DCs suggested that MyD88 signaling is dispensable for BCG-induced DC survival. NF-κB is one of the key regulators of innate immune responses. We observed that pharmacological inhibition of NF-κB abrogated BCG-mediated increase in DC survival and expression of anti-apoptotic proteins. These findings provide a novel insight into the effect of BCG on DC physiology.
机译：卡介苗（卡介苗）是唯一可用的抗结核疫苗，也用于治疗浅表性膀胱癌。 BCG介导的针对结核和膀胱癌的保护作用已显示依赖于其诱导优异的CD4 +和CD8 + T细胞反应的能力。由于T细胞反应的程度由树突状细胞（DC）寿命定义，我们检查了BCG对DC存活及其潜在机制的影响。观察到，BCG刺激以剂量依赖性方式提高DC存活率并延长DC寿命。与热灭活的卡介苗相比，活卡介苗导致更高的DC存活率。 FITC-Annexin V染色显示BCG通过抑制细胞凋亡促进DC存活。一致地，在BCG刺激的DC中观察到抗凋亡蛋白Bcl-2和Bcl-xL的更高表达。 Bcl-2和Bcl-xL的药理抑制作用大大降低了BCG的DC存活率。 BCG刺激的野生型和MyD88？/？DCs的可比生存表明，MyD88信号对于BCG诱导的DC生存是不可或缺的。 NF-κB是先天免疫反应的关键调节因子之一。我们观察到，NF-κB的药理学抑制作用消除了BCG介导的DC存活率和抗凋亡蛋白表达的增加。这些发现为BCG对DC生理学的影响提供了新颖的见解。

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