Cronobacter sakazakii ATCC 29544 Translocated Human Brain Microvascular Endothelial Cells via Endocytosis, Apoptosis Induction, and Disruption of Tight Junction.
Cronobacter sakazakii ATCC 29544 Translocated Human Brain Microvascular Endothelial Cells via Endocytosis, Apoptosis Induction, and Disruption of Tight Junction.
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阪崎克罗诺杆菌 ATCC 29544 通过内吞作用、诱导凋亡和破坏紧密连接使人脑微血管内皮细胞易位。
DOI：
10.3389/fmicb.2021.675020
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发表时间：
2021
影响因子：
5.2
通讯作者：
Xia X
中科院分区：
文献类型：
--
作者：
Jin T;Guan N;Du Y;Zhang X;Li J;Xia X
阪崎克罗诺杆菌（C. sakazakii）是一种新兴的机会性食源性病原体，可引起新生儿坏死性小肠结肠炎、脑膜炎、新生儿和婴儿败血症，死亡率较高。细菌跨人脑微血管内皮细胞 (HBMEC) 的转胞吞作用对于坂崎梭菌诱发新生儿脑膜炎至关重要。然而，很少有研究关注坂崎梭菌转运 HBMEC 的机制。本研究探讨了 C. sakazakii 在 HBMEC 上的易位过程。 C. sakazakii菌株能够有效地粘附、侵入HBMEC并在细胞内存活。在四个测试菌株中，菌株 ATCC 29544 在 HBMEC 单层上表现出最高的转位效率。通过透射电子显微镜在坂崎梭菌感染的 HBMEC 中检测到含有细菌的细胞内内体。感染后内吞相关蛋白CD44、Rab5、Rab7和LAMP2增加，而组织蛋白酶L的水平没有变化。坂崎棒杆菌诱导 HBMEC 中 TLR4/NF-κB 炎症信号通路激活，导致 NO 产生增加，IL-8、IL-6、TNF-α、IL-1β、iNOS 和 COX-2 mRNA 水平升高。阪崎梭菌感染还引起 LDH 释放、caspase-3 激活和 HBMEC 凋亡。同时，Dextran-FITC 通透性增加和跨上皮电阻降低表明坂崎梭菌破坏了 HBMEC 单层的紧密连接，紧密连接相关蛋白 ZO-1 和 Occludin 水平的降低证实了这一点。这些发现表明，坂崎梭菌诱导细胞内细菌内吞作用、刺激炎症和细胞凋亡、破坏 HBMEC 中的单层紧密连接，这些因素共同导致细菌易位。
Cronobacter sakazakii (C. sakazakii) is an emerging opportunistic foodborne pathogen that can cause neonatal necrotizing enterocolitis, meningitis, sepsis in neonates and infants with a relatively high mortality rate. Bacterial transcytosis across the human brain microvascular endothelial cells (HBMEC) is vital for C. sakazakii to induce neonatal meningitis. However, few studies focus on the mechanisms by which C. sakazakii translocates HBMEC. In this study, the translocation processes of C. sakazakii on HBMEC were explored. C. sakazakii strains could effectively adhere to, invade and intracellularly survive in HBMEC. The strain ATCC 29544 exhibited the highest translocation efficiency across HBMEC monolayer among four tested strains. Bacteria-contained intracellular endosomes were detected in C. sakazakii-infected HBMEC by a transmission electron microscope. Endocytosis-related proteins CD44, Rab5, Rab7, and LAMP2 were increased after infection, while the level of Cathepsin L did not change. C. sakazakii induced TLR4/NF-κB inflammatory signal pathway activation in HBMEC, with increased NO production and elevated mRNA levels of IL-8, IL-6, TNF-α, IL-1β, iNOS, and COX-2. C. sakazakii infection also caused LDH release, caspase-3 activation, and HBMEC apoptosis. Meanwhile, increased Dextran-FITC permeability and decreased trans epithelial electric resistance indicated that C. sakazakii disrupted tight junction of HBMEC monolayers, which was confirmed by the decreased levels of tight junction-related proteins ZO-1 and Occludin. These findings suggest that C. sakazakii induced intracellular bacterial endocytosis, stimulated inflammation and apoptosis, disrupted monolayer tight junction in HBMEC, which all together contribute to bacterial translocation.
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影响因子：
3.4
作者：
Kim, KJ;Elliott, SJ;Kim, KS
通讯作者：
Kim, KS
影响因子：
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Pizarro-Cerda, Javier
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2.8
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Quinn, Frederick D.