Transcellular Passage of Neisseria meningitidis across a Polarized Respiratory Epithelium

Thomas C. Sutherland; Paola Quattroni; Rachel M. Exley; Christoph M. Tang

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Transcellular Passage of Neisseria meningitidis across a Polarized Respiratory Epithelium

机译：脑膜炎奈瑟氏球菌跨极化呼吸道上皮细胞的跨细胞通道

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Neisseria meningitidis is a major cause of sepsis and meningitis but is also a common commensal, present in the nasopharynx of between 8 and 20% of healthy individuals. During carriage, the bacterium is found on the surface of the nasopharyngeal epithelium and in deeper tissues, while to develop disease the meningococcus must spread across the respiratory epithelium and enter the systemic circulation. Therefore, investigating the pathways by which N. meningitidis crosses the epithelial barrier is relevant for understanding carriage and disease but has been hindered by the lack of appropriate models. Here, we have established a physiologically relevant model of the upper respiratory epithelial cell barrier to investigate the mechanisms responsible for traversal of N. meningitidis. Calu-3 human respiratory epithelial cells were grown on permeable cell culture membranes to form polarized monolayers of cells joined by tight junctions. We show that the meningococcus crosses the epithelial cell barrier by a transcellular route; traversal of the layer did not disrupt its integrity, and bacteria were detected within the cells of the monolayer. We demonstrate that successful traversal of the epithelial cell barrier by N. meningitidis requires expression of its type 4 pili (Tfp) and capsule and is dependent on the host cell microtubule network. The Calu-3 model should be suitable for dissecting the pathogenesis of infections caused by other respiratory pathogens, as well as the meningococcus.

机译：脑膜炎奈瑟氏球菌是败血症和脑膜炎的主要原因，但也是常见的症状，存在于8-20％的健康个体的鼻咽中。在运输过程中，细菌被发现在鼻咽上皮的表面和更深的组织中，而为了发展疾病，脑膜炎球菌必须在呼吸道上皮中扩散并进入全身循环。因此，调查 N的途径。脑膜炎越过上皮屏障与理解运输和疾病有关，但由于缺乏合适的模型而受到阻碍。在这里，我们已经建立了上呼吸道上皮细胞屏障的生理相关模型，以研究负责遍历 N的机制。 Calu-3人呼吸道上皮细胞生长在可渗透的细胞培养膜上，形成紧密连接的极化细胞单层。我们显示脑膜炎球菌通过跨细胞途径穿过上皮细胞屏障。遍历该层不会破坏其完整性，并且在单层细胞内检测到细菌。我们证明了 N成功穿越了上皮细胞屏障。脑膜炎需要表达其4型菌毛（Tfp）和荚膜，并且依赖于宿主细胞微管网络。 Calu-3模型应适合剖析其他呼吸道病原体以及脑膜炎球菌引起的感染的发病机理。 展开▼

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《Infection and immunity》 |2010年第9期|共16页

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Thomas C. Sutherland; Paola Quattroni; Rachel M. Exley; Christoph M. Tang;
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中图分类医学免疫学;

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专利

1. Transcellular Passage of Neisseria gonorrhoeae Involves Pilus Phase Variation [J] . Dag Ilver, Helena K?llstr?m, Staffan Normark, Infection and immunity . 1998,第2期

机译：淋病奈瑟氏球菌的跨细胞通道涉及Pilus相变。

2. Absence of mucosal immunity in the human upper respiratory tract to the commensal bacteria Neisseria lactamica but not pathogenic Neisseria meningitidis during the peak age of nasopharyngeal carriage. [J] . Vaughan AT, Gorringe A, Davenport V, The Journal of Immunology: Official Journal of the American Association of Immunologists . 2009,第4期

机译：在鼻咽运输高峰期，人上呼吸道对共生细菌乳酸奈瑟氏菌缺乏黏膜免疫，但对病原性脑膜炎奈瑟氏菌没有。

3. Absence of Mucosal Immunity in the Human Upper Respiratory Tract to the Commensal Bacteria Neisseria lactamica but Not Pathogenic Neisseria meningitidis during the Peak Age of Nasopharyngeal Carriage [J] . Andrew T. Vaughan, Andrew Gorringe, Victoria Davenport, The journal of immunology . 2009,第4期

机译：在鼻咽支架高峰时期，人类上呼吸道对普通细菌乳酸奈瑟菌的黏膜免疫缺乏，但对致病性脑膜炎奈瑟氏菌的缺乏

4. Fatal meningococcal meningitidis in a baby caused by serogroup C Neisseria meningitidis belonging to ST-4821 complex [C] . Hui Han, Haishan Li, Yu Yang, International Conference on Human Health and Medical Engineering. . 2014

机译：致命的脑膜炎球菌脑膜脑膜脑膜脑膜脑膜炎症患者由Serogroup C Neisseria Meningitidis属于ST-4821复合物

5. Biochemical Assays of the Neisseria meningitidis Serogroup W Capsule Polymerase [D] . Sharyan, Abeer. 2018

机译：Neisseria Meningitidis血清群的生化测定胶囊聚合酶

6. Transcellular Passage of Neisseria meningitidis across a Polarized Respiratory Epithelium [O] . Thomas C. Sutherland, Paola Quattroni, Rachel M. Exley, 2010

机译：脑膜炎奈瑟氏球菌跨极化呼吸道上皮的跨细胞通道

7. Transcellular passage of Neisseria meningitidis across a polarized respiratory epithelium. [O] . Sutherland, TC, Quattroni, P, Exley, RM, 2010

机译：脑膜炎奈瑟氏球菌跨极化呼吸道上皮的跨细胞通道。

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4. A群奈瑟氏脑膜炎球菌荚膜多糖-破伤风类毒素结合疫苗的制备及其免疫原性研究 [J] . 刘方蕾 ,吴兵 ,杜琳 . 微生物学免疫学进展 . 2005,第002期

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1. 含重组菌毛蛋白的抗淋病奈瑟氏球茵或脑膜炎奈瑟氏球菌的疫苗 [P] . 中国专利： CN1245512C . 2006.03.15

2. 含重组菌毛蛋白的抗淋病奈瑟氏球茵或脑膜炎奈瑟氏球菌的疫苗 [P] . 中国专利： CN1298446A . 2001-06-06

3. Vaccine composition, processes for immunization against neisseria gonorrhoeae and to prepare a vaccine composition, isolated and purified DNA sequence, plasmid, host cell, process for producing a chimeric recombinant pilin protein from neisseria gonorrhoeae and neisseria meningitidis, chimeric recombinant protein isolated and purified from neisseria gonorhoeae and neisseria meningitidis, and, process for immunization against neisseria muningitidis [P] . 外国专利： BR9910005A . 2001-01-16

机译：疫苗组合物，针对淋病奈瑟氏球菌的免疫方法以及制备疫苗组合物，分离和纯化的DNA序列，质粒，宿主细胞，从淋病奈瑟氏球菌和脑膜炎奈瑟氏球菌生产嵌合重组菌毛蛋白的方法，从奈瑟氏球菌分离和纯化的嵌合重组蛋白淋病奈瑟菌和脑膜炎奈瑟氏球菌，以及针对慕尼黑菌的免疫接种方法

4. pencicillin-binding protein, nucleic acid, antibody or antibody fragment, medicament, pharmaceutical composition, uses of at least one penicillin-binding protein or fragment or variant or fragment thereof, of at least one nucleic acid and of at least one antibody or antibody fragment, in vitro antibody detection methods directed against neisseria meningitidis infection from a penicillin-binding protein, nucleic acid, antibody or an antibody fragment, pharmaceutical composition of at least one penicillin-binding protein or fragment or variant or variant thereof, of at least one nucleic acid and at least one antibody directed against neisseria meningitidis infection from a biological sample of a mammal and in vitro diagnosis of neisseria miningitidis infection from a biological sample from a mammal and monoclonal antibody [P] . 外国专利： BRPI0610802A2 . 2016-11-16

机译：青霉素结合蛋白，核酸，抗体或抗体片段，药物，药物组合物，至少一种青霉素结合蛋白或其片段或变异体或片段，至少一种核酸和至少一种抗体或抗体片段的用途，针对脑膜炎奈瑟菌的青霉素结合蛋白，核酸，抗体或抗体片段感染的体外抗体检测方法，至少一种青霉素结合蛋白或其片段或变异体或变异体，至少一种核酸的药物组合物酸和至少一种针对哺乳动物生物样品中脑膜炎奈瑟氏菌感染的抗体以及来自哺乳动物生物样品中的矿业性奈瑟氏球菌感染的体外诊断和单克隆抗体

5. DNA FRAGMENT ENCODING NEISSERIA MEMINGITIDIS STRAIN B:4:P1:15 EXTERNAL MEMBRANE PROTEIN, EXTERNAL MEMBRANE PROTEIN OF NEISSERIA MENINGITIDIS, RECOMBINANT PLASMID DNA PM-6, STRAIN OF BACTERIUM ESCHERICHIA COLI HBM64, METHOD OF PRODUCING PROTEIN OF NEISSERIA MENINGITIDIS EXTERNAL MEMBRANE, VACCINE COMPOSITION [P] . 外国专利： RU2132383C1 . 1999-06-27

机译：膜状奈瑟球菌菌株B：4：P1：15的DNA片段膜外蛋白，脑膜炎奈瑟氏菌的外部膜蛋白，重组质粒DNA PM-6，大肠杆菌蓝细菌HBM64菌株，产肠溶酶的方法

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Transcellular Passage of Neisseria meningitidis across a Polarized Respiratory Epithelium

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