Burkholderia pseudomallei-loaded cells act as a Trojan horse to invade the brain during endotoxemia.
Burkholderia pseudomallei-loaded cells act as a Trojan horse to invade the brain during endotoxemia.
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DOI：
10.1038/s41598-018-31778-8
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发表时间：
2018-09-11
影响因子：
4.6
通讯作者：
Chen YS
中科院分区：
文献类型：
--
作者：
Hsueh PT;Lin HH;Liu CL;Ni WF;Chen YL;Chen YS
神经性类鼻疽发生在人类和动物身上；然而，病原体类鼻疽伯克霍尔德杆菌侵入中枢神经系统（CNS）的机制仍不清楚。 B. 装载假鼻疽的 Ly6C 细胞被建议作为假定的门户；然而，在类鼻疽期间，脂多糖 (LPS) 会破坏血脑屏障 (BBB)。本研究旨在测试内毒素血症期间是否发生特洛伊木马样机制。脑细胞因子、趋化因子、细胞粘附分子的表达水平；星形胶质细胞、小胶质细胞和内皮细胞的激活；使用类鼻疽伯克氏菌、泰国伯克利氏杆菌、新洋葱伯克霍尔德氏菌和多食伯尔氏杆菌 LPS 诱导的大脑评估血管通透性增加和脑浸润白细胞。因此，内毒素血症患者的大脑存在不同程度的血脑屏障损伤。根据上述介质/指标，B. multivorans LPS 诱导的大脑表现出最高水平的破坏性 BBB。将装载类鼻疽伯克氏菌的 Ly6C 细胞或游离类鼻疽伯克氏菌以相同的细菌浓度 (103 CFU) 过继转移到这些不同的内毒素血症小鼠组中。在任何内毒素血症组中，用装载假鼻疽伯克氏菌的 Ly6C 细胞处理的动物大脑中的细菌载量和脑膜中性粒细胞浸润病例数均高于用游离假鼻疽伯克氏菌诱导的大脑中的细菌载量和中性粒细胞浸润病例数。特别是，这些结果在 B. multivorans LPS 诱导的大脑中是可重复的。我们认为，在脓毒症或内毒素血症条件下，即使存在高度的 BBB 破坏，装载类鼻疽伯克氏菌的细胞也可以充当特洛伊木马，并且比游离的类鼻疽伯克氏菌更有效地入侵中枢神经系统。
Neurologic melioidosis occurs in both human and animals; however, the mechanism by which the pathogen Burkholderia pseudomallei invades the central nervous system (CNS) remains unclear. B. pseudomallei-loaded Ly6C cells have been suggested as a putative portal; however, during melioidosis, lipopolysaccharide (LPS) can drive disruption of the blood-brain barrier (BBB). This study aims to test whether the Trojan horse-like mechanism occurs during endotoxemia. The expression levels of cerebral cytokines, chemokines and cell adhesion molecules; the activation of astrocytes, microglia and endothelial cells; and the increased vascular permeability and brain-infiltrating leukocytes were evaluated using B. pseudomallei, B. thailandensis, B. cenocepacia and B. multivorans LPS-induced brains. Accordingly, different degrees of BBB damage in those brains with endotoxemia were established. The B. multivorans LPS-induced brain exhibited the highest levels of disruptive BBB according to the above mediators/indicators. Into these distinct groups of endotoxemic mice, B. pseudomallei-loaded Ly6C cells or free B. pseudomallei were adoptively transferred at equal bacterial concentrations (103 CFU). The bacterial load and number of cases of meningeal neutrophil infiltration in the brains of animals treated with B. pseudomallei-loaded Ly6C cells were higher than those in brains induced by free B. pseudomallei in any of the endotoxemic groups. In particular, these results were reproducible in B. multivorans LPS-induced brains. We suggest that B. pseudomallei-loaded cells can act as a Trojan horse and are more effective than free B. pseudomallei in invading the CNS under septic or endotoxemic conditions even when there is a high degree of BBB disruption.
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