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首页> 外文期刊>PLoS Pathogens >Autophagy Controls BCG-Induced Trained Immunity and the Response to Intravesical BCG Therapy for Bladder Cancer
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Autophagy Controls BCG-Induced Trained Immunity and the Response to Intravesical BCG Therapy for Bladder Cancer

机译：自噬控制BCG诱导的训练有素的免疫力和对膀胱癌的intravishical BCG治疗的响应

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The anti-tuberculosis-vaccine Bacillus Calmette-Guérin (BCG) is the most widely used vaccine in the world. In addition to its effects against tuberculosis, BCG vaccination also induces non-specific beneficial effects against certain forms of malignancy and against infections with unrelated pathogens. It has been recently proposed that the non-specific effects of BCG are mediated through epigenetic reprogramming of monocytes, a process called trained immunity. In the present study we demonstrate that autophagy contributes to trained immunity induced by BCG. Pharmacologic inhibition of autophagy blocked trained immunity induced in vitro by stimuli such as β–glucans or BCG. Single nucleotide polymorphisms (SNPs) in the autophagy genes ATG2B (rs3759601) and ATG5 (rs2245214) influenced both the in vitro and in vivo training effect of BCG upon restimulation with unrelated bacterial or fungal stimuli. Furthermore, pharmacologic or genetic inhibition of autophagy blocked epigenetic reprogramming of monocytes at the level of H3K4 trimethylation. Finally, we demonstrate that rs3759601 in ATG2B correlates with progression and recurrence of bladder cancer after BCG intravesical instillation therapy. These findings identify a key role of autophagy for the nonspecific protective effects of BCG.
机译：抗结核病 - 疫苗芽孢杆菌（Bcgette-guérin（BCG）是世界上使用最广泛的疫苗。除了对结核病的影响外，BCG疫苗接种还对某些形式的恶性肿瘤和无关病原体的感染诱导非特异性的有益效果。最近据提出，BCG的非特异性效果通过单核细胞的表观遗传重编程来介导，该过程称为培训的免疫力。在本研究中，我们证明自噬有助于BCG诱导的培训免疫力。通过刺激诸如β-葡聚糖或BCG的体外诱导的自噬抑制的药理学抑制。在自噬基因ATG2B（RS3759601）和ATG5（RS2245214）中的单个核苷酸多态性（SNP）影响了BCG的体外和体内训练效果，并在用无关的细菌或真菌刺激的重新刺激时进行了影响。此外，在H3K4三甲基化水平下，对自噬的自噬障碍的脑膜脑重编程的药理或遗传抑制。最后，我们证明了ATG2B的RS3759601与BCG膀胱内滴注治疗后膀胱癌的进展和复发相关。这些发现识别自噬对BCG的非特异性保护作用的关键作用。

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