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. 2021 Feb;210(1):13-32.
doi: 10.1007/s00430-020-00695-x. Epub 2020 Nov 18.

Analysis of complement deposition and processing on Chlamydia trachomatis

Mads Lausen  1 , Mikkel Eggert Thomsen  2 , Gunna Christiansen  2   3 , Nichlas Karred  2 , Allan Stensballe  2 , Tue Bjerg Bennike  2 , Svend Birkelund  2
Affiliations

Analysis of complement deposition and processing on Chlamydia trachomatis

Mads Lausen et al. Med Microbiol Immunol. 2021 Feb.

Abstract

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.

Keywords: B-cells; C3; Chlamydia trachomatis; Complement; Mass spectrometry; Opsonization.

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References

    1. Rowley J, Vander Hoorn S, Korenromp E et al (2019) Chlamydia, gonorrhoea, trichomoniasis and syphilis: global prevalence and incidence estimates, 2016. Bull World Health Org 97:548–562. https://doi.org/10.2471/BLT.18.228486 - DOI - PubMed
    1. Davies B, Turner KME, Frølund M et al (2016) Risk of reproductive complications following chlamydia testing: a population-based retrospective cohort study in Denmark. Lancet Infect Dis 16:1057–1064. https://doi.org/10.1016/S1473-3099(16)30092-5 - DOI - PubMed
    1. Elwell C, Mirrashidi K, Engel J (2016) Chlamydia cell biology and pathogenesis. Nat Rev Microbiol 14:385–400. https://doi.org/10.1038/nrmicro.2016.30 - DOI - PubMed - PMC
    1. Zuck M, Sherrid A, Suchland R et al (2016) Conservation of extrusion as an exit mechanism for Chlamydia. Pathog Dis 74:ftw093. https://doi.org/10.1093/femspd/ftw093
    1. Hvid M, Baczynska A, Deleuran B et al (2007) Interleukin-1 is the initiator of Fallopian tube destruction during Chlamydia trachomatis infection. Cell Microbiol 9:2795–2803. https://doi.org/10.1111/j.1462-5822.2007.00996.x - DOI - PubMed