Down-regulation of CD46 by piliated Neisseria gonorrhoeae.

Down-regulation of CD46 by piliated Neisseria gonorrhoeae.
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DOI:
10.1084/jem.20031159
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发表时间:
2003-11-03
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Atkinson JP
Atkinson JP
中科院分区:
其他
文献类型:
--
作者:
Gill DB;Koomey M;Cannon JG;Atkinson JP

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人膜辅因子蛋白(CD 46)保护宿主细胞免受补体攻击,并可能作为致病性奈瑟氏球菌的受体发挥作用。我们评估了暴露于淋病奈瑟菌后人宫颈细胞系ME-180中CD 46的表达。有毛淋球菌而非无毛淋球菌粘附于细胞,6 h时CD 46表面表达减少80%,并持续至少24 h。这种反应需要最低感染复数为10,并且不能被CD 46抗体阻止。CD 46下调不归因于细胞内滞留或mRNA或蛋白质合成的整体或特异性关闭。在上清液中发现大量的CD 46,表明该蛋白质的特异性脱落。缺乏菌毛收缩蛋白PilT的粘附性淋球菌没有下调CD 46,但PilT表达的去抑制恢复了CD 46的下调。在用不能诱导CD 46下调的淋球菌变体实验性感染人类志愿者后,重新分离出表现出CD 46下调的该菌株的变体。菌毛介导的淋球菌与人上皮细胞的相互作用导致病原体诱导的宿主细胞环境的操纵,其中膜蛋白通过释放到周围环境中而从上皮细胞中去除。
Human membrane cofactor protein (CD46) protects host cells against complement attack and may function as a receptor for pathogenic Neisseriae. We assessed CD46 expression in the human cervical cell line ME-180 after exposure to Neisseria gonorrhoeae. Piliated but not nonpiliated gonococci adhered to cells and produced up to an 80% reduction in CD46 surface expression by 6 h that persisted for at least 24 h. This response required a minimum multiplicity of infection of 10 and was not prevented by antibodies to CD46. CD46 down-regulation was not attributable to intracellular retention or a global or specific shutdown of mRNA or protein synthesis. Substantial quantities of CD46 were found in the supernatants, indicating a specific shedding of this protein. Adherent gonococci lacking the pilus retraction protein PilT did not down-regulate CD46 but de-repression of pilT expression restored CD46 down-regulation. After experimental infection of human volunteers with a gonococcal variant incapable of inducing CD46 down-regulation, variants of this strain were reisolated that exhibited CD46 down-regulation. Pilus-mediated interactions of gonococci with human epithelial cells results in a pathogen-induced manipulation of the host cell environment in which a membrane protein is removed from epithelial cells by liberation into the surrounding milieu.
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