Species-specific interaction of Streptococcus pneumoniae with human complement factor H.
Species-specific interaction of Streptococcus pneumoniae with human complement factor H.
复制标题
肺炎链球菌与人类补体因子H的物种特异性相互作用。
DOI：
10.4049/jimmunol.181.10.7138
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发表时间：
2008-11-15
影响因子：
4.4
通讯作者：
Zhang, Jing-Ren
中科院分区：
文献类型：
--
作者：
Lu, Ling;Ma, Zhuo;Jokiranta, T. Sakari;Whitney, Adeline R.;DeLeo, Frank R.;Zhang, Jing-Ren
肺炎链球菌作为共生生物自然定植于鼻咽部，有时会引起远处组织部位的感染。这种细菌在鼻咽定植和传播感染过程中具有很强的抵抗宿主先天免疫的能力。肺炎链球菌募集补体因子 H (FH) 的能力被认为是针对补体介导的细菌清除的细菌免疫逃避机制，因为 FH 是补体替代途径抑制剂。肺炎链球菌通过先前定义的胆碱结合蛋白 A (CbpA)（肺炎链球菌的主要表面蛋白）的 FH 结合域招募 FH。在这项研究中，我们表明 CbpA 与人类 FH 结合，但不与迄今为止测试的小鼠和其他动物物种的 FH 蛋白结合。因此，删除菌株 D39 中 CbpA 的 FH 结合结构域并不会导致菌血症小鼠模型中肺炎球菌菌血症或毒力水平的明显变化。此外，这种物种特异性肺炎球菌与 FH 的相互作用发生在血液和脑脊液 (CSF) 的多种肺炎球菌分离株中。最后，我们对人和小鼠吞噬细胞和补体系统的吞噬实验提供了额外的证据来支持我们的假设，即 CbpA 作为人类肺炎球菌对补体介导的宿主防御的抵抗力的细菌决定因素。
Streptococcus pneumoniae naturally colonizes the nasopharynx as a commensal organism and sometimes causes infections in remote tissue sites. This bacterium is highly capable of resisting host innate immunity during nasopharyngeal colonization and disseminating infections. The ability to recruit complement factor H (FH) by S. pneumoniae has been implicated as a bacterial immune evasion mechanism against complement-mediated bacterial clearance because FH is a complement alternative pathway inhibitor. S. pneumoniae recruits FH through a previously defined FH-binding domain of choline-binding protein A (CbpA), a major surface protein of S. pneumoniae. In this study, we show that CbpA binds to human FH but not to the FH proteins of mouse and other animal species tested thus far. Accordingly, deleting the FH-binding domain of CbpA in strain D39 did not result in obvious change in the levels of pneumococcal bacteremia or virulence in a bacteremia mouse model. Furthermore, this species-specific pneumococcal interaction with FH was shown to occur in multiple pneumococcal isolates from the blood and cerebrospinal fluid (CSF). Finally, our phagocytosis experiments with human- and mouse phagocytes and complement systems provide additional evidence to support our hypothesis that CbpA acts as a bacterial determinant for pneumococcal resistance to complement-mediated host defense in humans.
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影响因子：
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作者：
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通讯作者：
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