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Suppression of human lymphocyte responses by oral spirochetes: a monocyte-dependent phenomenon
Abstract:
Spirochetes have been implicated in the pathogenesis of several human infections including syphilis, yaws, Lyme disease, and periodontal diseases. We examined soluble sonic extracts of oral spirochetes (Treponema denticola and T. vincentii) for their ability to alter human lymphocyte function. These organisms were isolated from subgingival plaque of patients with periodontitis. We found that sonicates of several but not all strains of T. denticola caused a dose-dependent inhibition of human lymphocyte responsiveness to Con A, PHA, PWM, and the recall antigen SKSD. Suppression involved alterations in DNA, RNA, and protein synthesis; there was no effect on cell viability. In contrast, sonicates of T. vincentii (medium-sized spirochetes) had no demonstrable effects on lymphocyte activation. The suppressive factor derived from T. denticola is heat-labile with a m.w. of approximately 100,000. To achieve maximal suppression, sonicates had to be added during the first 24 hr of incubation; there was no inhibition observed when added at 48 or 72 hr (along with 3H-TdR). Suppression was dependent on the presence of adherent monocytes; removal of these cells prevented spirochete-induced suppression of lymphocyte proliferation. Furthermore, the combination of indomethacin and catalase were able to reverse (or prevent) the inhibitory effects of the spirochete extracts, demonstrating a requirement for both prostaglandins and hydrogen peroxide. The potential role of such suppressive factors in periodontal disease is discussed.
Insights
Oral spirochetes, specifically Treponema denticola, can suppress human lymphocyte function by affecting DNA, RNA, and protein synthesis. This immune suppression, crucial in periodontal disease, requires monocytes, prostaglandins, and hydrogen peroxide.
Area of Science:
- Oral microbiology
- Immunology
- Periodontal disease pathogenesis
Background:
- Spirochetes are linked to various human diseases, including periodontal infections.
- Oral spirochetes like Treponema denticola and T. vincentii reside in subgingival plaque of periodontitis patients.
Purpose of the Study:
- To investigate the impact of oral spirochete extracts on human lymphocyte function.
- To identify the mechanisms and factors involved in spirochete-induced immune modulation.
Main Methods:
- Soluble sonic extracts of T. denticola and T. vincentii were prepared from oral isolates.
- Lymphocyte responsiveness to mitogens (Con A, PHA, PWM) and recall antigens (SKSD) was assessed.
- Effects on DNA, RNA, and protein synthesis, cell viability, and the role of monocytes, prostaglandins, and hydrogen peroxide were examined.
Main Results:
- T. denticola extracts, but not T. vincentii, caused dose-dependent inhibition of lymphocyte responsiveness.
- Suppression involved altered nucleic acid and protein synthesis without affecting cell viability.
- The suppressive factor from T. denticola is heat-labile, approximately 100,000 m.w., and requires early incubation (24 hr).
- Monocytes are essential for spirochete-induced suppression, which can be reversed by indomethacin and catalase, indicating roles for prostaglandins and hydrogen peroxide.
Conclusions:
- Treponema denticola possesses factors that suppress human lymphocyte function, potentially contributing to periodontal disease pathogenesis.
- The immune suppressive mechanism involves prostaglandins and hydrogen peroxide and is dependent on the presence of monocytes.