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Toxic effect of human polymorphonuclear leukocytes on Chlamydia trachomatis
Abstract:
The effect of human polymorphonuclear leukocytes (PMNs) on Chlamydia trachomatis was studied. Both trachoma (B/TW-5/OT) and lymphogranuloma venereum (L2/434/Bu) biotypes were rapidly inactivated by exposure to human PMNs. A decrease of 3 to 3.5 logs in viable count was observed after 60 min of incubation at a chlamydia-to-PMN ratio of 1:10. Both chlamydial biotypes were also rapidly inactivated by the cell-free myeloperoxidase-H2O2-halide system. A decrease in infectivity titer of 4 to 5 logs for TW-5 and complete inactivation of 434 were seen after 30 min of incubation. The microbicidal effect was prevented by the deletion of each component of the system or by the addition of the peroxidase inhibitors cyanide or azide. PMNs from myeloperoxidase-deficient patients inactivated chlamydiae normally, whereas PMNs from patients with chronic granulomatous disease, although strongly chlamydicidal, were less effective than normal PMNs in the activation of TW-5 (2-log drop in viable organisms versus a 3 to 3.5-log drop). The chlamydicidal activity of PMNs from patients with chronic granulomatous disease and normal PMNs were comparable against the 434 biotype. These studies suggest that the myeloperoxidase system, or indeed oxygen-dependent antimicrobial systems, are not essential for the chlamydicidal activity of PMNs.
Insights
Human polymorphonuclear leukocytes (PMNs) effectively inactivate Chlamydia trachomatis. The myeloperoxidase system is not essential for this potent chlamydicidal activity, indicating other oxygen-dependent antimicrobial systems are involved.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Chlamydia trachomatis is a significant human pathogen.
- Polymorphonuclear leukocytes (PMNs) are key immune cells involved in combating bacterial infections.
- The specific mechanisms by which PMNs exert their antimicrobial effects against Chlamydia are not fully elucidated.
Purpose of the Study:
- To investigate the in vitro effect of human PMNs on Chlamydia trachomatis.
- To determine the role of the myeloperoxidase (MPO) system in PMN-mediated inactivation of Chlamydia.
- To compare the activity of PMNs from patients with specific immune deficiencies against Chlamydia.
Main Methods:
- Incubation of Chlamydia trachomatis (trachoma and lymphogranuloma venereum biotypes) with human PMNs at various ratios.
- Exposure of Chlamydia to cell-free myeloperoxidase-H2O2-halide system.
- Assessment of chlamydial viability and infectivity titers.
- Utilizing PMNs from myeloperoxidase-deficient patients and patients with chronic granulomatous disease (CGD).
Main Results:
- Human PMNs rapidly inactivated both trachoma and lymphogranuloma venereum biotypes of Chlamydia trachomatis.
- A cell-free myeloperoxidase-H2O2-halide system also demonstrated rapid microbicidal effects.
- PMNs from myeloperoxidase-deficient patients showed normal chlamydicidal activity.
- PMNs from CGD patients were less effective against the trachoma biotype but comparable against the lymphogranuloma venereum biotype compared to normal PMNs.
Conclusions:
- The myeloperoxidase system is not essential for the chlamydicidal activity of human PMNs.
- Oxygen-dependent antimicrobial systems may not be critical for PMN-mediated inactivation of Chlamydia trachomatis.
- PMNs possess potent mechanisms for controlling Chlamydia infections, independent of MPO activity.