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.

沙眼衣原体( C. trachomatis ) 是全球性传播细菌感染的主要原因，每年有超过 1.2 亿例病例。沙眼衣原体感染与女性严重的生殖并发症有关，例如宫外孕和输卵管不孕。感染通常持续很长时间，与免疫病理学有关，并且不能引起保护性免疫，这使得反复感染很常见。沙眼衣原体感染所涉及的免疫机制仅被部分了解。小鼠感染模型表明，补体系统在原发性衣原体感染过程中在保护性免疫和免疫病理学中都发挥着重要作用感染。然而，补体介导的针对沙眼衣原体的免疫仅存在有限的结构和机制证据。为了扩展我们目前在该主题上的知识，我们使用基于全面深入质谱的蛋白质组学分析了沙眼衣原体上的全局补体沉积。我们显示因子 B、备解素和 C4b 与沙眼衣原体结合，证明沙眼衣原体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，导致终末补体途径的启动和 C5b、C6、C7、C8、C9 在沙眼衣原体上的沉积. 有趣的是，使用免疫电子显微镜，我们发现 C5b-9 沉积偶尔发生，并且仅在极少数情况下形成完整的裂解终端复合物，这可能是由负调节剂玻连蛋白和凝聚素的存在引起的。最后，C3 的裂解分析表明，沉积的 C3b 被降解为调理素 iC3b 和 C3dg，并且这种补体调理作用促进了沙眼衣原体与人类 B 细胞的结合。