Rab32 GTPase, as a direct target of miR-30b/c, controls the intracellular survival of Burkholderia pseudomallei by regulating phagosome maturation
Rab32 GTPase, as a direct target of miR-30b/c, controls the intracellular survival of Burkholderia pseudomallei by regulating phagosome maturation
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Rab32 GTPase 作为 miR-30b/c 的直接靶标，通过调节吞噬体成熟来控制类鼻疽伯克霍尔德氏菌的细胞内存活
DOI：
10.1371/journal.ppat.1007879
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发表时间：
2019-06-01
期刊：
影响因子：
6.7
通讯作者：
Mao, Xu-hu
中科院分区：
文献类型：
--
作者：
Hu, Zhi-qiang;Rao, Cheng-long;Mao, Xu-hu
类鼻疽伯克霍尔德氏菌是一种革兰氏阴性兼性胞内细菌，可引起类鼻疽病。专职吞噬细胞代表了对抗入侵病原体的先天防御的关键第一道防线。这些细胞对病原体的摄取涉及吞噬体的形成，吞噬体通过与早期和晚期内吞囊泡融合而成熟，从而杀死摄入的微生物。宿主Rab GTP酶是病原体吞噬后囊泡运输的中心调节因子。然而，目前还不清楚RaB GTP酶如何与B相互作用。pseudomallei来调节含细菌的吞噬体的运输和成熟。在这里，我们发现，主机Rab 32在介导抗微生物活性中起着重要的作用，通过促进吞噬体成熟，在感染的早期阶段与B。假鼻疽我们证明Rab 32的表达水平通过下调miR-30 B/30 c在B中的合成而增加。类鼻疽感染的巨噬细胞。随后，我们证明了B.假鼻疽暂时存在于Rab 32阳性隔室中，具有晚期内吞特征。Rab 32增强吞噬体酸化，促进B融合。含有类鼻疽的吞噬体与溶酶体一起激活组织蛋白酶D，导致B的细胞内生长受限。假鼻疽此外，Rab 32依赖于其三磷酸鸟苷/二磷酸鸟苷（GTP/GDP）结合状态介导吞噬体成熟。最后，我们报告了以前未被认识到的miR-30 B/30 c在调节B中的作用。通过靶向巨噬细胞中的Rab 32来促进含有假鼻疽的吞噬体成熟。总之，我们提供了一个新的见解宿主免疫调节细胞通路对B。类鼻疽感染部分依赖于Rab 32运输途径，其调节吞噬体成熟并增强巨噬细胞中该细菌的杀伤。
Burkholderia pseudomallei is a gram-negative, facultative intracellular bacterium, which causes a disease known as melioidosis. Professional phagocytes represent a crucial first line of innate defense against invading pathogens. Uptake of pathogens by these cells involves the formation of a phagosome that matures by fusing with early and late endocytic vesicles, resulting in killing of ingested microbes. Host Rab GTPases are central regulators of vesicular trafficking following pathogen phagocytosis. However, it is unclear how Rab GTPases interact with B. pseudomallei to regulate the transport and maturation of bacterial-containing phagosomes. Here, we showed that the host Rab32 plays an important role in mediating antimicrobial activity by promoting phagosome maturation at an early phase of infection with B. pseudomallei. And we demonstrated that the expression level of Rab32 is increased through the downregulation of the synthesis of miR-30b/30c in B. pseudomallei infected macrophages. Subsequently, we showed that B. pseudomallei resides temporarily in Rab32-positive compartments with late endocytic features. And Rab32 enhances phagosome acidification and promotes the fusion of B. pseudomallei-containing phagosomes with lysosomes to activate cathepsin D, resulting in restricted intracellular growth of B. pseudomallei. Additionally, Rab32 mediates phagosome maturation depending on its guanosine triphosphate/guanosine diphosphate (GTP/GDP) binding state. Finally, we report the previously unrecognized role of miR-30b/30c in regulating B. pseudomallei-containing phagosome maturation by targeting Rab32 in macrophages. Altogether, we provide a novel insight into the host immune-regulated cellular pathway against B. pseudomallei infection is partially dependent on Rab32 trafficking pathway, which regulates phagosome maturation and enhances the killing of this bacterium in macrophages.