Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
General Clinical Research Center, Medical Research Department, Taipei Veterans General Hospital, Taipei, Taiwan.
Sci Rep. 2018 Sep 11;8(1):13632. doi: 10.1038/s41598-018-31778-8.
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 (10 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.
神经型类鼻疽病发生在人和动物中;然而，病原菌伯克霍尔德氏菌（Burkholderia pseudomallei）入侵中枢神经系统（CNS）的机制仍不清楚。已提出载有伯克霍尔德氏菌的 Ly6C 细胞作为可能的门户；然而，在类鼻疽病中，脂多糖（LPS）可导致血脑屏障（BBB）破坏。本研究旨在测试内毒素血症期间是否发生类似特洛伊木马的机制。使用伯克霍尔德氏菌、泰国伯克霍尔德氏菌、洋葱伯克霍尔德氏菌和鲍曼不动杆菌 LPS 诱导的大脑评估大脑细胞因子、趋化因子和细胞黏附分子的表达水平；星形胶质细胞、小胶质细胞和内皮细胞的激活；以及血管通透性增加和脑浸润白细胞。因此，在这些具有内毒素血症的大脑中建立了不同程度的 BBB 损伤。根据上述介质/指标，鲍曼不动杆菌 LPS 诱导的大脑显示出最高程度的破坏性 BBB。将载有伯克霍尔德氏菌的 Ly6C 细胞或游离伯克霍尔德氏菌以相同的细菌浓度（10 CFU）被动转移到这些不同组的内毒素血症小鼠中。在任何内毒素血症组中，用载有伯克霍尔德氏菌的 Ly6C 细胞处理的动物的大脑中的细菌负荷和脑膜中性粒细胞浸润的病例数均高于用游离伯克霍尔德氏菌诱导的大脑。特别是，这些结果在鲍曼不动杆菌 LPS 诱导的大脑中是可重复的。我们建议，载有伯克霍尔德氏菌的细胞可以作为特洛伊木马，并且在脓毒症或内毒素血症条件下，即使 BBB 破坏程度很高，也比游离的伯克霍尔德氏菌更有效地入侵 CNS。
