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首页> 外文期刊>Infection and immunity >Klebsiella pneumoniae Induces an Inflammatory Response in an In Vitro Model of Blood-Retinal Barrier
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Klebsiella pneumoniae Induces an Inflammatory Response in an In Vitro Model of Blood-Retinal Barrier

机译：肺炎克雷伯菌在血液-视网膜屏障的体外模型中诱导炎症反应。

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Klebsiella pneumoniae has become an important pathogen in recent years. Although most cases of K. pneumoniae endogenous endophthalmitis occur via hematogenous spread, it is not yet clear which microbial and host factors are responsible for the ability of K. pneumoniae to cross the blood-retinal barrier (BRB). In the present study, we show that in an in vitro model of BRB based on coculturing primary bovine retinal endothelial cells (BREC) and primary bovine retinal pericytes (BRPC), K. pneumoniae infection determines changes of transendothelial electrical resistance (TEER) and permeability to sodium fluorescein. In the coculture model, bacteria are able to stimulate the enzyme activities of endothelial cytosolic and Ca2+-independent phospholipase A2s (cPLA2 and iPLA2). These results were confirmed by the incremental expression of cPLA2, iPLA2, cyclo-oxygenase-1 (COX1), and COX2 in BREC, as well as by cPLA2 phosphorylation. In supernatants of K. pneumoniae-stimulated cocultures, increases in prostaglandin E2 (PGE2), interleukin-6 (IL-6), IL-8, and vascular endothelial growth factor (VEGF) production were found. Incubation with K. pneumoniae in the presence of arachidonoyl trifluoromethyl ketone (AACOCF3) or bromoenol lactone (BEL) caused decreased PGE2 and VEGF release. Scanning electron microscopy and transmission electron microscopy images of BREC and BRPC showed adhesion of K. pneumoniae to the cells, but no invasion occurred. K. pneumoniae infection also produced reductions in pericyte numbers; transfection of BREC cocultured with BRPC and of human retinal endothelial cells (HREC) cocultured with human retinal pericytes (HRPC) with small interfering RNAs (siRNAs) targeted to cPLA2 and iPLA2 restored the pericyte numbers and the TEER and permeability values. Our results show the proinflammatory effect of K. pneumoniae on BREC, suggest a possible mechanism by which BREC and BRPC react to the K. pneumoniae infection, and may provide physicians and patients with new ways of fighting blinding diseases.
机译：近年来，肺炎克雷伯菌已成为重要的病原体。尽管大多数肺炎克雷伯菌内源性眼内炎病例是通过血源性扩散发生的，但尚不清楚哪些微生物和宿主因素是导致肺炎克雷伯菌穿过血视网膜屏障（BRB）的能力。在本研究中，我们显示，在基于共培养原代牛视网膜内皮细胞（BREC）和原代牛视网膜周细胞（BRPC）的BRB体外模型中，肺炎克雷伯菌感染决定了跨内皮电阻（TEER）和通透性的变化荧光素钠。在共培养模型中，细菌能够刺激内皮细胞溶质和不依赖Ca2 +的磷脂酶A2（cPLA2和iPLA2）的酶活性。这些结果通过BREC中cPLA2，iPLA2，环加氧酶-1（COX1）和COX2的增量表达以及cPLA2磷酸化得到了证实。在肺炎克雷伯菌刺激的共培养物的上清液中，发现前列腺素E2（PGE2），白介素6（IL-6），IL-8和血管内皮生长因子（VEGF）的产生增加。在存在花生四烯酰基三氟甲基酮（AACOCF3）或溴烯醇内酯（BEL）的情况下与肺炎克雷伯菌一起孵育，会降低PGE2和VEGF的释放。 BREC和BRPC的扫描电子显微镜和透射电子显微镜图像显示肺炎克雷伯菌粘附于细胞，但未发生侵袭。肺炎克雷伯菌感染也导致周细胞数量减少。与BRPC共培养的BREC和与人视网膜周细胞（HRPC）共培养的人视网膜内皮细胞（HREC）的转染，同时靶向cPLA2和iPLA2的小干扰RNA（siRNA）可以恢复周细胞数以及TEER和通透性值。我们的结果表明肺炎克雷伯菌对BREC的促炎作用，表明BREC和BRPC对肺炎克雷伯菌感染起反应的可能机制，并可能为医师和患者提供对抗致盲性疾病的新方法。

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