Department of Health Science and Technology, Aalborg University, Fredrik Bajers Vej 3b, 9220, Aalborg Ø, Denmark.
Department of Biomedicine, Aarhus University, Wilhelms Meyers Allé 4, 8000, Aarhus, Denmark.
Med Microbiol Immunol. 2021 Feb;210(1):13-32. doi: 10.1007/s00430-020-00695-x. Epub 2020 Nov 18.
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）是全球导致性传播细菌感染的主要原因，每年有超过 1.2 亿例病例。C. trachomatis 感染与女性严重的生殖并发症有关，如宫外孕和输卵管不孕。感染通常持续时间长，与免疫病理学有关，并且无法引起保护性免疫，这使得反复感染很常见。C. trachomatis 感染涉及的免疫机制仅部分被理解。鼠类感染模型表明，补体系统在初次衣原体感染期间的保护性免疫和免疫病理学中发挥重要作用。然而，关于补体介导的针对 C. trachomatis 的免疫作用，仅存在有限的结构和机制证据。为了扩展我们在这一主题上的现有知识，我们使用全面深入的基于质谱的蛋白质组学分析了 C. trachomatis 上的全球补体沉积。我们表明，因子 B、备解素和 C4b 与 C. trachomatis 结合，表明 C. trachomatis 诱导的补体激活至少通过两条激活途径进行。补体激活导致 C3 和 C5 激活产物的切割和沉积，导致末端补体途径的启动以及 C5b、C6、C7、C8、C9 在 C. trachomatis 上的沉积。有趣的是，使用免疫电子显微镜，我们显示 C5b-9 沉积是散在发生的，仅在极少数情况下形成完整的溶解末端复合物，可能是由于存在负调节剂 vitronectin 和 clusterin。最后，C3 的切割分析表明，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 C. trachomatis 与人 B 细胞的结合。
