Department of Biological Sciences, Eck Institute for Global Health, Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN, USA.
Department of Biological Sciences, Eck Institute for Global Health, Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN, USA
EMBO Rep. 2019 Mar;20(3). doi: 10.15252/embr.201846613. Epub 2019 Jan 25.
Extracellular vesicles (EVs) have been shown to carry microbial components and function in the host defense against infections. In this study, we demonstrate that () RNA is delivered into macrophage-derived EVs through an SecA2-dependent pathway and that EVs released from -infected macrophages stimulate a host RIG-I/MAVS/TBK1/IRF3 RNA sensing pathway, leading to type I interferon production in recipient cells. These EVs also promote, in a RIG-I/MAVS-dependent manner, the maturation of -containing phagosomes through a noncanonical LC3 pathway, leading to increased bacterial killing. Moreover, treatment of -infected macrophages or mice with a combination of moxifloxacin and EVs, isolated from -infected macrophages, significantly lowered bacterial burden relative to either treatment alone. We hypothesize that EVs, which are preferentially removed by macrophages , can be combined with effective antibiotics as a novel approach to treat drug-resistant TB.
细胞外囊泡 (EVs) 已被证明携带微生物成分，并在宿主抗感染防御中发挥作用。在这项研究中，我们证明 () RNA 通过依赖 SecA2 的途径被递送至巨噬细胞衍生的 EVs 中，并且来自感染的巨噬细胞释放的 EVs 刺激宿主 RIG-I/MAVS/TBK1/IRF3 RNA 感应途径，导致受者细胞中产生 I 型干扰素。这些 EVs 还通过非典型 LC3 途径以 RIG-I/MAVS 依赖的方式促进含有 的吞噬体的成熟，从而导致细菌杀伤增加。此外，用莫西沙星和从感染的巨噬细胞中分离出的 EVs 联合治疗感染的巨噬细胞或小鼠，与单独使用任一药物相比，显著降低了细菌负荷。我们假设 EVs 优先被巨噬细胞清除，可以与有效的抗生素联合使用，作为一种治疗耐药性结核病的新方法。
