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CD46-Independent Binding of Neisserial Type IV Pili and the Major Pilus Adhesin, PilC, to Human Epithelial Cells

机译:奈瑟氏球菌IV型菌毛和主要毛状细胞粘附素PilC对人上皮细胞的CD46依赖性结合

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Neisseria gonorrhoeae is a gram-negative bacterial pathogen which infects the human mucosal epithelium. An early critical event in neisserial infection is the type IV pilus-mediated adherence to the host cell. The PilC protein, located on the pilus tip, has earlier been identified as the major pilus adhesin. Previous studies suggested that the cell surface protein CD46 is a pilus receptor for Neisseria. We investigated the role of CD46 in pilus-mediated gonococcal infection of epithelial cells. Differences in binding efficiencies of piliated gonococci as well as purified pilus adhesin PilC2 on human epithelial cell lines did not correlate to the level of surface-expressed CD46. Additionally, no binding of piliated gonococci or PilC2 protein was observed on CD46-transfected CHO and MDCK cells. Furthermore, specific down-regulation of CD46 expression in human epithelial cell lines by RNA interference did not alter the binding efficiency of piliated gonococci or purified PilC2 protein, although other CD46-dependent processes, such as measles virus infection and C3b cleavage, were significantly reduced. These data support the notion that pilus-mediated gonococcal infection of epithelial cells can occur in a CD46-independent manner, thus questioning the function of CD46 as an essential pilus receptor for pathogenic neisseriae.
机译:淋病奈瑟菌是一种革兰氏阴性细菌病原体,可感染人类粘膜上皮。奈瑟菌感染的早期关键事件是IV型菌毛介导的对宿主细胞的粘附。位于菌毛尖端的PilC蛋白较早被鉴定为主要菌毛粘附素。先前的研究表明,细胞表面蛋白CD46是奈瑟菌的菌毛受体。我们调查了CD46在菌毛介导的淋球菌感染上皮细胞中的作用。人上皮细胞系上毛状球菌和纯化的菌毛粘附素PilC2的结合效率差异与表面表达的CD46水平无关。此外,在CD46转染的CHO和MDCK细胞上未观察到纤毛性淋球菌或PilC2蛋白的结合。此外,尽管显着降低了其他依赖CD46的过程,例如麻疹病毒感染和C3b裂解,但通过RNA干扰,人上皮细胞系中CD46表达的特异性下调并没有改变毛状球菌或纯化的PilC2蛋白的结合效率。 。这些数据支持以下观念:菌毛介导的淋球菌感染上皮细胞可以以CD46无关的方式发生,因此质疑CD46作为致病性奈瑟氏菌必不可少的菌毛受体的功能。

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