Infection of human monocyte-derived macrophages with Chlamydia trachomatis induces apoptosis of T cells: a potential mechanism for persistent infection.
Viruses can escape T-cell surveillance by infecting macrophages and thereby induce apoptosis of noninfected T cells. This ability had not been demonstrated for bacteria. We investigated whether infection of macrophages with the important human pathogen Chlamydia trachomatis can induce T-cell apoptosis. Because Chlamydia-Mycoplasma coinfection is a frequent event, the ability of Mycoplasma fermentans-infected macrophages to induce T-cell apoptosis was also studied. Infected macrophages were cocultivated with autologous T cells in different activation states. Propidium iodide-based fluorescence-activated cell sorter analysis demonstrated that macrophages infected with viable chlamydiae induced T-cell death. Apoptosis was identified as the mode of death induction by using a terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling assay. Induction of T-cell death was macrophage dependent. Incubation of T cells with infectious chlamydiae in the absence of macrophages did not lead to T-cell apoptosis. UV irradiation of chlamydiae diminished the ability to induce death. T-cell death was induced by a cell-free supernatant of infected macrophages. Not only phytohemagglutinin-preactivated T cells but also non-mitogen-preactivated T cells were susceptible to C. trachomatis-induced apoptosis. In contrast, M. fermentans infection of macrophages did not induce T-cell death. Coinfection had no additional effect. In summary, intracellular chlamydial infection of macrophages can induce T-cell apoptosis. Apoptosis induction by chlamydiae possibly explains how persistently infected macrophages escape T-cell surveillance and why the Chlamydia-specific T-cell response is diminished during persistent chlamydial infection.
Jendro
M C
MC
Department of Rheumatology, Social Medicine, and Health System Research, Medical School Hannover, Hannover, Germany. Jendro.Michael@Mh-Hannover.de
Deutsch
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Körber
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Köhler
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Kuipers
J G
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Krausse-Opatz
B
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Westermann
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Raum
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Zeidler
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D017209:Apoptosis; D002692:Chlamydia trachomatis / Q000472:pathogenicity* / Q000528:radiation effects; D006801:Humans; D008213:Lymphocyte Activation; D008264:Macrophages / Q000382:microbiology* / Q000502:physiology; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000502:physiology*; D014466:Ultraviolet Rays
D010835:Phytohemagglutinins