Chlamydia trachomatis-infected macrophages induce apoptosis of activated T cells by secretion of tumor necrosis factor-alpha in vitro.
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-alpha (TNF-alpha) concentrations were measured by enzyme-linked immunosorbent assay. Antagonists of TNF-alpha, 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-alpha from infected macrophages. Inhibition of secretory TNF-alpha by the monoclonal anti-TNF-alpha 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-alpha derived from infected macrophages is an important apoptosis factor for T cell apoptosis induced by C. trachomatis-infected cells.
Department of Rheumatology, Medical School Hannover, 30623 Hannover, Germany. michael.jendro@uniklinik-saarland.de
Michael C
MC
Jendro
Frederik
F
Fingerle
Tobias
T
Deutsch
Andrea
A
Liese
Lars
L
Köhler
Jens G
JG
Kuipers
Elke
E
Raum
Michael
M
Martin
Henning
H
Zeidler
D000068879:Adalimumab; D000906:Antibodies; D000911:Antibodies, Monoclonal / Q000276:immunology; D061067:Antibodies, Monoclonal, Humanized; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D002374:Catalase / Q000378:metabolism; D002450:Cell Communication; D018929:Cell Culture Techniques; D002692:Chlamydia trachomatis / Q000472:pathogenicity*; D018920:Coculture Techniques; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology*; D008562:Membrane Glycoproteins / Q000276:immunology; D010835:Phytohemagglutinins / Q000378:metabolism; D011419:Propidium; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D019014:fas Receptor / Q000494:pharmacology
D000906:Antibodies; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D010835:Phytohemagglutinins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D011419:Propidium; D002374:Catalase; D000068879:Adalimumab