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Chlamydia trachomatis-infected macrophages induce apoptosis of activated T cells by secretion of tumor necrosis factor-α in vitro

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Abstract

Chlamydia trachomatis-infected macrophages induce T cell apoptosis. This ability might promote intracellular survival of Chlamydia and perpetuate chronic chlamydial infection. The purpose of this study was to examine the molecular mechanisms by which C. trachomatis-infected macrophages induce T cell apoptosis. Monocytes and T cells were isolated from the peripheral blood of healthy donors. Macrophages were infected with C. trachomatis, and autologous T cells were stimulated by mitogen. After 6 days, both populations were cultured together using a two-chamber transwell membrane system to differentiate between mechanisms involving either cell-to-cell contact or secretion of apoptotic factors. Apoptotic T cells were identified by propidium iodide through-flow cytometry, and tumor necrosis factor-α (TNF-α) concentrations were measured by enzyme-linked immunosorbent assay. Antagonists of TNF-α, the Fas (CD95) molecule, TNF-related apoptosis-inducing ligand (TRAIL), and catalase were added to differentiate between the pathways of apoptosis. C. trachomatis-infected macrophages significantly induced T cell apoptosis by cell-to-cell contact (mean ± standard deviation, 30±4%; P<0.001) and by humoral mechanisms (mean ± standard deviation, 22±3%, P<0.001). Humoral apoptosis was mediated by secretion of TNF-α from infected macrophages. Inhibition of secretory TNF-α by the monoclonal anti-TNF-α antibody adalimumab (D2E7) blocked T cell death in vitro. In contrast, T cell apoptosis mediated by cell-to-cell contact was not inhibited by the different anti-apoptotic reagents. In summary, TNF-α derived from infected macrophages is an important apoptosis factor for T cell apoptosis induced by C. trachomatis-infected cells.

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Acknowledgements

Our work was supported by grants from the Bundesministerium für Bildung und Forschung 01 G/9950, the European Community BIOMED BMH4-CT-98-3605 and the Medical School Hannover HILF 19311022. We appreciate the laboratory work of Mrs. Schmidt and thank Dr. H. Kupper, Abbott GmbH (Ludwigshafen, Germany), for kindly providing us with adalimumab; Dr. C. Fiehn (Medizinische Poliklinik, Heidelberg) for rIL-2 and Prof. R. Schwinzer (Medizinische Hochschule Hannover) for the Fas ligand-transfected cell line 293h and Dr. Kessels and Prof. Linde from the bloodbank of the Annastift (Hannover, Germany) for the buffy coats from healthy donors.

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  1. Michael C. Jendro

    Present address: Department of Medicine, Saarland University Medical School, 66421, Homburg/Saar, Germany

Authors and Affiliations

  1. Department of Rheumatology, Medical School Hannover, 30623, Hannover, Germany

    Michael C. Jendro, Frederik Fingerle, Tobias Deutsch, Andrea Liese, Lars Köhler, Jens G. Kuipers & Henning Zeidler

  2. Department of Epidemiology, Social Medicine and Health System Research, Medical School Hannover, 30623, Hannover, Germany

    Elke Raum

  3. Department of Molecular Pharmacology, Medical School Hannover, 30623, Hannover, Germany

    Michael Martin

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  1. Michael C. Jendro
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Correspondence to Michael C. Jendro.

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Jendro, M.C., Fingerle, F., Deutsch, T. et al. Chlamydia trachomatis-infected macrophages induce apoptosis of activated T cells by secretion of tumor necrosis factor-α in vitro. Med Microbiol Immunol 193, 45–52 (2004). https://doi.org/10.1007/s00430-003-0182-1

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