Infection of human monocyte-derived macrophages with Chlamydia trachomatisinduces 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 demonst rated for bacteria. We investigated whether infection of macrophages with t he important human pathogen Chlamydia trachomatis can induce T-cell apoptos is. Because Chlamydia-Mycoplasma coinfection is a frequent event, the abili ty 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 mod e of death induction by using a terminal deoxynucleotidyltransferase-mediat ed dUTP-biotin nick end labeling assay. Induction of T-cell death was macro phage dependent. Incubation of T cells with infectious chlamydiae in the ab sence of macrophages did not lead to T-cell apoptosis. UV irradiation of ch lamydiae diminished the ability to induce death. T-cell death was induced b y a cell-free supernatant of infected macrophages. Not only phytohemaggluti nin-preactivated T cells but also non-mitogen-preactivated T cells were sus ceptible to C. trachomatis-induced apoptosis. In contrast, M. fermentans in fection of macrophages did not induce T-cell death. Coinfection had no addi tional effect. In summary, intracellular chlamydial infection of macrophage s can induce T-cell apoptosis. Apoptosis induction by chlamydiae possibly e xplains how persistently infected macrophages escape T-cell surveillance an d why the Chlamydia-specific T-cell response is diminished during persisten t chlamydial infection.