Interaction of Pneumococcal Histidine Triad Proteins with Human Complement
Interaction of Pneumococcal Histidine Triad Proteins with Human Complement
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DOI：
10.1128/iai.00811-09
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发表时间：
2010-05-01
影响因子：
3.1
通讯作者：
Vakevainen, Merja
中科院分区：
文献类型：
--
作者：
Melin, Merit;Di Paolo, Emmanuel;Vakevainen, Merja
肺炎球菌组氨酸三联体（Pht）蛋白PhtA、PhtB、PhtD和PhtE形成一组保守的肺炎球菌表面蛋白。人类暴露于肺炎球菌后产生Pht蛋白抗体，小鼠免疫接种提供了针对脓毒症和肺炎的保护性免疫，并减少了鼻咽定植。Pht蛋白是包含在多组分肺炎球菌蛋白疫苗中的候选者。它们在肺炎球菌感染中的生物学功能尚不清楚，但已提出在补体抑制中的作用。我们测量了四种遗传背景下野生型和Pht突变菌株的补体沉积：肺炎链球菌D39（血清型2）和R36 A（D39的未包封衍生物）以及血清型3、4和19 F菌株。将PspA和PspC单突变体和双突变体与野生型和Pht缺陷型D39菌株进行比较。测量因子H与细菌细胞、裂解物和蛋白质抗原的结合。所有四种Pht蛋白的缺失（Pht（-））导致血清型4菌株上的C3沉积增加，但在其他菌株上不增加。Pht抗原不结合因子H，并且Pht蛋白的缺失不影响细菌裂解物与因子H的结合。当通过流式细胞术测量结合时，Pht（-）突变血清型4菌株与野生型菌株结合的因子H略少。Pht蛋白可能在免疫逃避中发挥作用，但其功能机制不太可能由H因子结合介导。Pht蛋白对补体沉积抑制的相对贡献可能受到其他肺炎球菌蛋白的存在的影响，并取决于遗传背景。
The pneumococcal histidine triad (Pht) proteins PhtA, PhtB, PhtD, and PhtE form a group of conserved pneumococcal surface proteins. Humans produce antibodies to Pht proteins upon exposure to pneumococcus, and immunization of mice has provided protective immunity against sepsis and pneumonia and reduced nasopharyngeal colonization. Pht proteins are candidates for inclusion in multicomponent pneumococcal protein vaccines. Their biological function in pneumococcal infections is not clear, but a role in complement inhibition has been suggested. We measured complement deposition on wild-type and Pht mutant strains in four genetic backgrounds: Streptococcus pneumoniae D39 (serotype 2) and R36A (unencapsulated derivative of D39) and strains of serotypes 3, 4, and 19F. PspA and PspC single and double mutants were compared to the wild-type and Pht-deficient D39 strains. Factor H binding was measured to bacterial cells, lysates, and protein antigens. Deletion of all four Pht proteins (Pht(-)) resulted in increased C3 deposition on the serotype 4 strain but not on the other strains. Pht antigens did not bind factor H, and deletion of Pht proteins did not affect factor H binding by bacterial lysates. The Pht(-) mutant serotype 4 strain bound slightly less factor H than the wild-type strain when binding was measured by flow cytometry. Pht proteins may play a role in immune evasion, but the mechanism of function is unlikely to be mediated by factor H binding. The relative contribution of Pht proteins to the inhibition of complement deposition is likely to be affected by the presence of other pneumococcal proteins and to depend on the genetic background.