Neisseria gonorrhoeae elicits membrane ruffling and cytoskeletal rearrangements upon infection of primary human endocervical and ectocervical cells
Neisseria gonorrhoeae elicits membrane ruffling and cytoskeletal rearrangements upon infection of primary human endocervical and ectocervical cells
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DOI：
10.1128/iai.68.9.5354-5363.2000
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发表时间：
2000-09-01
影响因子：
3.1
通讯作者：
Apicella, MA
中科院分区：
文献类型：
--
作者：
Edwards, JL;Shao, JQ;Apicella, MA
淋病奈瑟菌是一种严格的人类病原体，主要通过与受感染个体的密切性接触传播。男性泌尿生殖道淋球菌感染已在实验性人类模型和尿道细胞培养系统中得到充分研究。最近的研究，使用组织培养细胞系统，提出了宫颈上皮淋球菌感染的女性的作用，然而，淋球菌感染的正常子宫颈的性质仍然存在争议，为了解决这个谜，我们已经开发了两个主要的人类宫颈上皮细胞系统从手术活检。淋球菌感染研究和电子显微镜显示，N。淋病能够感染和侵入子宫颈内膜和外宫颈。发现入侵主要以肌动蛋白依赖的方式发生，但似乎不需要细菌或宿主宫颈细胞从头合成蛋白质。膜皱褶似乎是由淋球菌引起的。与膜皱褶一致，淋球菌被发现居住在巨胞饮体内，并观察到肌动蛋白相关蛋白的集中积累发生在淋球菌感染。临床来源的宫颈活检的电子显微镜显示，层状伪足的形成和细胞骨架的变化，提示膜皱褶，也发生在自然获得性淋球菌性宫颈炎的妇女的宫颈上皮。这些研究证明了N.淋病感染并侵入正常子宫颈的子宫内膜和外宫颈。淋球菌引起的皱褶是一个新的发现，可能是唯一的宫颈上皮。
Neisseria gonorrhoeae is a strict human pathogen that is, primarily, transmitted by close sexual contact with an infected individual. Gonococcal infection of the male urogenital tract has been well studied in experimental human models and in urethral cell culture systems. Recent studies, using tissue culture cell systems, have suggested a role for the cervical epithelium in gonococcal infection of females; however, the nature of gonococcal infection of the normal uterine cervix remains controversial, To address this enigma, we have developed two primary human cervical epithelial cell systems from surgical biopsies. Gonococcal infection studies and electron microscopy show that N. gonorrhoeae is capable of infecting and invading both the endo- and the ectocervix. Invasion was found to occur primarily in an actin-dependent manner, but it does not appear to require de novo protein synthesis by either the bacterium or the host cervical cell. Membrane ruffles appear to be induced in response to gonococci. Consistent with membrane ruffling, gonococci were found residing within macropinosomes, and a concentrated accumulation of actin-associated proteins was observed to occur in response to gonococcal infection. Electron microscopy of clinically derived cervical biopsies show that lamellipodia formation and cytoskeletal changes, suggestive of membrane ruffles, also occur in the cervical epithelium of women with naturally acquired gonococcal cervicitis. These studies demonstrate the ability of N. gonorrhoeae to infect and invade both the endo- and the ectocervix of the normal uterine cervix. Gonococcal induced ruffling is a novel finding and may be unique to the cervical epithelium.