Human fibrinogen bound to Streptococcus pyogenes M protein inhibits complement deposition via the classical pathway
Human fibrinogen bound to Streptococcus pyogenes M protein inhibits complement deposition via the classical pathway
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DOI：
10.1111/j.1365-2958.2005.04527.x
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发表时间：
2005-04-01
影响因子：
3.6
通讯作者：
Lindahl, G
中科院分区：
文献类型：
--
作者：
Carlsson, F;Sandin, C;Lindahl, G
人纤维蛋白原（Fg）与许多病原菌表达的表面蛋白结合，并参与不同的宿主-病原体相互作用，但结合Fg的作用仍不清楚。在这里，我们分析了结合化脓性链球菌M蛋白，一个主要的毒力因子，赋予抵抗吞噬的Fg的作用。对M5系统的研究表明，缺乏Fg结合区的染色体突变体完全不能抵抗吞噬作用，表明结合的Fg在毒力中起关键作用。补体在S.即使在非免疫条件下，化脓性链球菌也通过经典途径发生，但被M5结合的Fg阻断，这减少了细菌表面上经典途径C3转化酶的量。M蛋白结合的Fg的这种性质可以解释其在吞噬抗性中的作用。以前的研究表明，许多M蛋白不结合Fg，但通过招募经典途径的抑制剂人C4 b结合蛋白（C4 BP）来干扰补体沉积和吞噬作用。因此，所有的M蛋白可以共享募集人血浆蛋白Fg或C4 BP的能力，其通过经典途径抑制补体沉积。我们的数据确定了一个新的功能，表面结合的纤维蛋白原，使我们能够提出一个统一的机制，M蛋白干扰先天免疫。
Human fibrinogen (Fg) binds to surface proteins expressed by many pathogenic bacteria and has been implicated in different host-pathogen interactions, but the role of bound Fg remains unclear. Here, we analyse the role of Fg bound to Streptococcus pyogenes M protein, a major virulence factor that confers resistance to phagocytosis. Studies of the M5 system showed that a chromosomal mutant lacking the Fg-binding region was completely unable to resist phagocytosis, indicating that bound Fg plays a key role in virulence. Deposition of complement on S. pyogenes occurred via the classical pathway even under non-immune conditions, but was blocked by M5-bound Fg, which reduced the amount of classical pathway C3 convertase on the bacterial surface. This property of M protein-bound Fg may explain its role in phagocytosis resistance. Previous studies have shown that many M proteins do not bind Fg, but interfere with complement deposition and phagocytosis by recruiting human C4b-binding protein (C4BP), an inhibitor of the classical pathway. Thus, all M proteins may share ability to recruit a human plasma protein, Fg or C4BP, which inhibits complement deposition via the classical pathway. Our data identify a novel function for surface-bound Fg and allow us to propose a unifying mechanism by which M proteins interfere with innate immunity.