Properdin is critical for antibody-dependent bactericidal activity against Neisseria gonorrhoeae that recruit C4b-binding protein.
Properdin is critical for antibody-dependent bactericidal activity against Neisseria gonorrhoeae that recruit C4b-binding protein.
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DOI：
10.4049/jimmunol.1102746
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发表时间：
2012-04-01
期刊：
影响因子：
--
通讯作者：
Ram S
中科院分区：
文献类型：
--
作者：
Gulati S;Agarwal S;Vasudhev S;Rice PA;Ram S
淋病是由淋球菌引起的一种性传播疾病，是世界范围内发病的重要原因。由于淋球菌对几乎所有种类的抗生素都出现了耐药性，因此需要一种安全有效的淋病疫苗。由单抗2C7定义的淋球菌脂低聚糖(LOS)表位正在被评估为基于抗体的疫苗的候选开发。针对淋球菌的免疫抗体需要克服淋球菌逃避补体的几种颠覆性机制，包括与C4b结合蛋白(C4BP；经典途径抑制物)和因子H(替代途径[AP]抑制物)的结合。AP募集，特别是备解素在协助特定抗体杀灭淋球菌方面的作用是本研究的主题。我们发现，只有那些与C4BP结合的淋球菌菌株才需要备解素才能被2C7杀死，而不结合C4BP的菌株即使在AP功能被阻断的情况下也能有效地被2C7杀死。C3在细菌上的沉积反映了杀菌效果。通过B因子结合测定，mAb2C7对AP的募集是以一种依赖于备解素的方式发生的。使用与C4BP结合能力不同的同基因突变菌株证实了这些发现。含有针对2C7 LOS表位的杀菌抗体的免疫人血清以及小鼠抗淋球菌抗血清，需要功能性备解素来杀死C4BP结合菌株，而不是C4BP非结合菌株。总而言之，这些数据表明，备解素在促进免疫抗体介导的补体依赖的淋球菌株的杀伤中发挥重要作用，淋球菌株通过招募C4BP抑制经典途径。
Gonorrhea, a sexually transmitted disease caused by Neisseria gonorrhoeae, is an important cause of morbidity worldwide. A safe and effective vaccine against gonorrhea is needed because of emerging resistance of gonococci to almost every class of antibiotic. A gonococcal lipooligosaccharide (LOS) epitope defined by the monoclonal antibody (mAb), 2C7, is being evaluated as a candidate for development of an antibody-based vaccine. Immune antibodies against N. gonorrhoeae need to overcome several subversive mechanisms whereby gonococcus evades complement, including binding to C4b-binding protein (C4BP; classical pathway inhibitor) and factor H (alternative pathway [AP] inhibitor). The role of AP recruitment and in particular properdin in assisting killing of gonococci by specific antibodies is the subject of this study. We show that only those gonococcal strains that bind C4BP require properdin for killing by 2C7, whereas strains that do not bind C4BP are efficiently killed by 2C7 even when AP function is blocked. C3 deposition on bacteria mirrored killing. Recruitment of the AP by mAb 2C7, as measured by factor B binding, occurred in a properdin-dependent manner. These findings were confirmed using isogenic mutant strains that differed in their ability to bind to C4BP. Immune human serum that contained bactericidal antibodies directed against the 2C7 LOS epitope as well as murine anti-gonococcal antiserum, required functional properdin to kill C4BP binding strains, but not C4BP non-binding strains. Collectively, these data point to an important role for properdin in facilitating immune antibody-mediated complement-dependent killing of gonococcal strains that inhibit the classical pathway by recruiting C4BP.
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影响因子：
36.8
作者：
FIGUEROA, JE;DENSEN, P
通讯作者：
DENSEN, P
DOI：
10.1073/pnas.95.18.10872
发表时间：
1998-09-01
影响因子：
11.1
作者：
Banerjee, A;Wang, R;Stein, DC
通讯作者：
Stein, DC
影响因子：
6.4
作者：
Gulati, S;McQuillen, DP;Rice, PA
通讯作者：
Rice, PA
影响因子：
20.3
作者：
Camous, Laurent;Roumenina, Lubka;Halbwachs-Mecarelli, Lise
通讯作者：
Halbwachs-Mecarelli, Lise
影响因子：
3.1
作者：
CANNON, JG;BLACK, WJ;STEWART, PW
通讯作者：
STEWART, PW