Analysis of complement deposition and processing on Chlamydia trachomatis
Analysis of complement deposition and processing on Chlamydia trachomatis
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DOI：
10.1007/s00430-020-00695-x
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发表时间：
2020-11-18
影响因子：
5.4
通讯作者：
Birkelund, Svend
中科院分区：
文献类型：
--
作者：
Lausen, Mads;Thomsen, Mikkel Eggert;Birkelund, Svend
沙眼衣原体（C.沙眼）是全世界性传播细菌感染的主要原因，每年有超过1.2亿例。C.沙眼感染与妇女的严重生殖并发症有关，如宫外孕和输卵管不孕症。感染通常是持久的，与免疫病理学相关，并且不能引起保护性免疫，这使得复发性感染很常见。对C.对沙眼感染的了解还很有限。小鼠感染模型表明，在原发性衣原体感染期间，补体系统在保护性免疫和免疫病理学中起重要作用。然而，只有有限的结构和机制的证据存在补体介导的免疫对C。沙眼为了扩展我们目前对这一主题的了解，我们分析了C.沙眼使用全面深入的质谱为基础的蛋白质组学。我们发现因子B、备解素和C4 B b与C结合。trachomatis表明C.沙眼诱导的补体激活通过至少两种激活途径进行。补体激活导致C3和C5激活产物的裂解和沉积，引起末端补体途径的启动和C5 b、C6、C7、C8、C9在C上的沉积。沙眼有趣的是，使用免疫电子显微镜，我们发现，C5 b-9沉积零星发生，只有在罕见的情况下形成完整的裂解终端复合物，可能是由负调节玻连蛋白和丛生蛋白的存在下引起的。最后，C3的裂解分析表明，沉积的C3 b被降解为调理素iC 3b和C3 dg，并且这种补体调理作用促进C。沙眼衣原体与人类B细胞的结合。
Chlamydia trachomatis (C. trachomatis) is the leading cause of sexually transmitted bacterial infections worldwide, with over 120 million annual cases. C. trachomatis infections are associated with severe reproductive complications in women such as extrauterine pregnancy and tubal infertility. The infections are often long lasting, associated with immunopathology, and fail to elicit protective immunity which makes recurrent infections common. The immunological mechanisms involved in C. trachomatis infections are only partially understood. Murine infection models suggest that the complement system plays a significant role in both protective immunity and immunopathology during primary Chlamydia infections. However, only limited structural and mechanistic evidence exists on complement-mediated immunity against C. trachomatis. To expand our current knowledge on this topic, we analyzed global complement deposition on C. trachomatis using comprehensive in-depth mass spectrometry-based proteomics. We show that factor B, properdin, and C4b bind to C. trachomatis demonstrating that C. trachomatis-induced complement activation proceeds through at least two activation pathways. Complement activation leads to cleavage and deposition of C3 and C5 activation products, causing initiation of the terminal complement pathway and deposition of C5b, C6, C7, C8, C9 on C. trachomatis. Interestingly, using immunoelectron microscopy, we show that C5b-9 deposition occurred sporadically and only in rare cases formed complete lytic terminal complexes, possibly caused by the presence of the negative regulators vitronectin and clusterin. Finally, cleavage analysis of C3 demonstrated that deposited C3b is degraded to the opsonins iC3b and C3dg and that this complement opsonization facilitates C. trachomatis binding to human B-cells.