Intracellular bacteria engage a STING-TBK1-MVB12b pathway to enable paracrine cGAS-STING signalling
Intracellular bacteria engage a STING-TBK1-MVB12b pathway to enable paracrine cGAS-STING signalling
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DOI：
10.1038/s41564-019-0367-z
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发表时间：
2019-04-01
影响因子：
28.3
通讯作者：
Paludan, Soren R.
中科院分区：
文献类型：
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作者：
Nandakumar, Ramya;Tschismarov, Roland;Paludan, Soren R.
先天免疫系统对于最终控制感染至关重要，但也可能导致病理学。单核细胞增生李斯特菌是一种胞内革兰氏阳性菌，是引起食源性疾病的主要原因。然而，重要的知识之间的相互作用L。单核细胞增多症和免疫系统仍然缺失。在这里，我们报告李斯特菌DNA被分选到感染细胞的细胞外囊泡（EV）中，并被递送到旁观者细胞，以刺激环鸟苷酸-腺苷酸合酶（cGAS）-干扰素基因（STING）途径的刺激因子。在土拉热弗朗西丝菌和嗜肺军团菌感染期间也观察到这一点。我们确定了多泡体蛋白MVB 12 b作为TANK结合激酶1磷酸化的靶点，TANK结合激酶1磷酸化对于将DNA分选为EV和刺激旁观者细胞至关重要。来自李斯特菌感染细胞的EV抑制T细胞增殖，并引发T细胞凋亡。总的来说，我们描述了一个途径EV介导的外源DNA传递到旁观者细胞，并建议细胞内细菌利用这一途径来损害抗菌防御。
The innate immune system is crucial for eventual control of infections, but may also contribute to pathology. Listeria monocytogenes is an intracellular Gram-positive bacteria and a major cause of food-borne disease. However, important knowledge on the interactions between L. monocytogenes and the immune system is still missing. Here, we report that Listeria DNA is sorted into extracellular vesicles (EVs) in infected cells and delivered to bystander cells to stimulate the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) pathway. This was also observed during infections with Francisella tularensis and Legionella pneumophila. We identify the multivesicular body protein MVB12b as a target for TANK-binding kinase 1 phosphorylation, which is essential for the sorting of DNA into EVs and stimulation of bystander cells. EVs from Listeria-infected cells inhibited T-cell proliferation, and primed T cells for apoptosis. Collectively, we describe a pathway for EV-mediated delivery of foreign DNA to bystander cells, and suggest that intracellular bacteria exploit this pathway to impair antibacterial defence.