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.

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。单核细胞增生李斯特菌是一种细胞内革兰氏阳性细菌，是食源性疾病的主要原因。然而，关于单增李斯特菌与免疫系统之间相互作用的重要知识仍然缺失。在此，我们报道李斯特菌DNA 被分选到受感染细胞的细胞外囊泡 (EV) 中，并递送至旁观者细胞，以刺激环鸟苷单磷酸 - 单磷酸腺苷合酶 (cGAS) - 干扰素基因刺激剂 (STING) 途径。在土拉弗朗西斯菌和嗜肺军团菌感染期间也观察到了这一点。我们确定多囊泡体蛋白 MVB12b 作为 TANK 结合激酶 1 磷酸化的靶标，这对于将 DNA 分选到 EV 中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，我们描述了一种 EV 介导的外源 DNA 传递至旁观细胞的途径，并表明细胞内细菌利用该途径来削弱抗菌防御。