CD66 carcinoembryonic antigens mediate interactions between Opa-expressing Neisseria gonorrhoeae and human polymorphonuclear phagocytes
CD66 carcinoembryonic antigens mediate interactions between Opa-expressing Neisseria gonorrhoeae and human polymorphonuclear phagocytes
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DOI：
10.1093/emboj/16.12.3435
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发表时间：
1997-06-16
期刊：
影响因子：
11.4
通讯作者：
Meyer, TF
中科院分区：
文献类型：
--
作者：
GrayOwen, SD;Dehio, C;Meyer, TF
人类淋病奈瑟菌在泌尿生殖组织中的定植，其特征是与含有明显活菌的多形核吞噬细胞（pmn）的化脓性渗出物有关。相位可变不透明性相关（Opa）外膜蛋白的不同变体形式介导淋病奈瑟菌通过人pmn的非调理结合和内化。利用覆盖试验和亲和分离技术，我们证明了表达Opa（52）的淋球菌与表达CD66表位的人癌胚抗原（CEA）家族成员之间的直接相互作用。合成Opa（52）的淋球菌和重组大肠杆菌菌株被转染表达CD66家族成员BGP （CD66a）、NCA （CD66c）、CGM1 （CD66d）和CEA （CD66e）的HeLa细胞株特异性结合和内化，而不表达CGM6 （CD66b）的HeLa细胞株特异性结合和内化。不表达不透明蛋白或上皮细胞侵袭相关的Opa的菌株（50）不能结合这些CEA家族成员。与它们不同的受体特异性一致，Opa（52）介导的相互作用可以被多克隆抗cea血清抑制，而Opa（50）的结合则被肝素抑制。使用激光共聚焦扫描显微镜，我们观察到表达Opa（52）的淋球菌在转染细胞系和感染PMNs上明显募集CD66抗原。这些数据表明CEA家族的成员构成了与淋病奈瑟菌相互作用和内化的细胞受体。
Colonization of urogenital tissues by the human pathogen Neisseria gonorrhoeae is characteristically associated with purulent exudates of polymorphonuclear phagocytes (PMNs) containing apparently viable bacteria. Distinct variant forms of the phase-variable opacity-associated (Opa) outer membrane proteins mediate the non-opsonized binding and internalization of N. gonorrhoeae by human PMNs. Using overlay assays and an affinity isolation technique, we demonstrate the direct interaction between Opa(52)-expressing gonococci and members of the human carcinoembryonic antigen (CEA) family which express the CD66 epitope. Gonococci and recombinant Escherichia coli strains synthesizing Opa(52) showed specific binding and internalization by transfected HeLa cell lines expressing the CD66 family members BGP (CD66a), NCA (CD66c), CGM1 (CD66d) and CEA (CD66e), but not that expressing CGM6 (CD66b). Bacterial strains expressing either no opacity protein or the epithelial cell invasion-associated Opa(50) do not bind these CEA family members. Consistent with their different receptor specificities, Opa(52)-mediated interactions could be inhibited by polyclonal anti-CEA sera, while Opa(50) binding was instead inhibited by heparin. Using confocal laser scanning microscopy, we observed a marked recruitment of CD66 antigen by Opa(52)-expressing gonococci on both the transfected cell lines and infected PMNs. These data indicate that members of the CEA family constitute the cellular receptors for the interaction with, and internalization of, N. gonorrhoeae.