Immunoregulatory properties of serum from patients with different stages of syphilis

Thompson, J J; Mangi, Richard J.; Lee, R; Dwyer, John M.

doi:10.1136/sti.56.4.210

Cited by 7 publications

(5 citation statements)

References 11 publications

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“…The host's immune system actively participates in the relentless pursuit and elimination of T. pallidum, while T. pallidum skillfully employs various mechanisms to evade immune recognition, such as suppression of host cellular immune responses. 34,35 Macrophages are the frontline cells of innate defence and play a crucial role in the process of T. pallidum infection. A previous study has demonstrated that Tp92, the outer membrane protein of T. pallidum, induces the death of human monocytes in the early stages of T. pallidum infection, which helps T. pallidum to escape recognition and elimination by the host innate immune system.…”

Section: Discussionmentioning

confidence: 99%

“…During T. pallidum infection, the interplay between the evasion strategies of T. pallidum and the host's innate and adaptive immune responses is a complex and dynamic battle. The host's immune system actively participates in the relentless pursuit and elimination of T. pallidum , while T. pallidum skillfully employs various mechanisms to evade immune recognition, such as suppression of host cellular immune responses 34,35 . Macrophages are the frontline cells of innate defence and play a crucial role in the process of T. pallidum infection.…”

Section: Discussionmentioning

confidence: 99%

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Treponema pallidum protein Tp47 induced prostaglandin E2 to inhibit the phagocytosis in human macrophages

Yi,

Xu,

et al. 2024

Acad Dermatol Venereol

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BackgroundDuring Treponema pallidum (T. pallidum) infection, the host's immune system actively engages in pursuit and elimination of T. pallidum, while T. pallidum skillfully employs various mechanisms to evade immune recognition. Macrophages exhibit incomplete clearance of T. pallidum in vitro and the underlying mechanism of how T. pallidum resists the attack of macrophage remains unclear.ObjectivesTo investigate the effect of T. pallidum membrane protein Tp47 on the phagocytosis of macrophages.MethodsTHP‐1‐derived macrophages were used to investigate the role of Tp47 in the secretion of Prostaglandin E2 (PGE2) in macrophages and the mechanism by which Tp47 induced the production of PGE2, as well as the impact of PGE2 on the macrophage's phagocytosis.ResultsTp47 (1–10 μg/mL) significantly inhibited the phagocytosis of latex beads and T. pallidum in macrophages (p ≤ 0.05). PGE2 production by macrophages could be induced by Tp47, and the phagocytic function of macrophages could be restored using PGE2 antibody. Tp47 produced PGE2 by activating the PERK/NF‐κB/COX‐2 pathway in macrophages. Inhibitors targeting PERK, NF‐κB and COX‐2, respectively, reduced the level of PGE2 and restored the phagocytic function of macrophages.ConclusionTp47‐induced PGE2 production via the PERK/NF‐κB/COX‐2 pathway contributed to macrophage phagocytosis inhibition, which potentially contributes to immune evasion during the T. pallidum infection.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Treponema pallidum protein Tp47 induced prostaglandin E2 to inhibit the phagocytosis in human macrophages

Yi,

Xu,

et al. 2024

Acad Dermatol Venereol

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“…In conclusion, it is important to stress the pitfalls inherent in interpreting in vitro data and determining the relevance it has, if any, to in vivo biological and clinical events. The presence of serum inhibitors has been used by some investigators (5,22,41,42,51,55) to promote a role for immunosuppression in early syphilis. This hypothesis purportedly explains the persistence of the infecting organisms during latency and the subsequent progression to tertiary disease.…”

Section: Discussionmentioning

confidence: 99%

Serum Regulation of In Vitro Lymphocyte Responses in Early Experimental Syphilis

1982

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Sera from rabbits with early experimental syphilis were tested for their effect on in vitro lymphocyte transformation responses to related specific antigens (sonicated T. pallidum), unrelated specific antigens (sheep erythrocytes), and the T cell mitogen, concanavalin A. Results were compared with responses in preinfection sera and in sera from sham-infected rabbits. Titration experiments in which normal serum was used indicated that optimal lymphocyte responsiveness is obtained with a final serum concentration of 1%. Under these conditions, no differences in concanavalin A stimulation were observed in cultures with syphilitic sera. Responses to sonicated T. pallidum were inhibited, but only by 17 to 25% when compared with the response in preinfection sera. In cultures containing 10% serum, inhibition of lymphocyte proliferation to sonicated T. pallidum antigens was evident with sera from all syphilitic animals from day 10 (55% inhibition) through day 31 (80% inhibition) of infection. Responses to concanavalin A and sheep erythrocytes were significantly inhibited by day 10 sera; only 20% of the sera tested demonstrated substantial nonspecific inhibitory capacity. No differences were evident among sera from any of the sham-infected animals or among the preinfection sera from either group. Pooled serum with high inhibitory activity was fractionated by ammonium sulfate precipitation, DEAE ion exchange chromatography, and Sephadex G-200 gel filtration. Two separate inhibitors were identified: (i) a low-molecular-weight, ammonium sulfate-soluble, nonspecific inhibitory fraction containing albumin and alpha-globulins with the capacity to inhibit both antigen and mitogen responses and (ii) a high-molecular-weight, ammonium sulfate-precipitable, inhibitory fraction containing alpha-globulin and FTA-ABS-reactive immunoglobulin M which affected only the antigen-specific response to sonicated T. pallidum. Immunodiffusion failed to detect immunoglobulin or T. pallidum antigens in either fraction. DEAE-purified immunoglobulin G from immune serum was not inhibitory.

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“…The evidence favoring suppression stems from the diminished in vitro mitogenic stimulation of peripheral blood lymphocytes from patients. This suppression is maximal during the secondary stage and is attributed to one or more serum factors (16,27). Since we found that the limitations of the initial IgG response were overcome just before the secondary stage, it seems unlikely that IgG production is connected to this postulated immune suppression.…”

Section: Si+mentioning

confidence: 99%

“…The slow development of host defense mechanisms on the one hand and the absence of positive results in certain in vivo and in vitro immunological tests (14,16,26,27) on the other could complement each other and led to the hypothesis that the immune system is suppressed during early syphilis. However, it is not clear whether some of these findings are * Corresponding author.…”

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confidence: 99%

Immunoglobulin G subclasses of fluorescent anti-Treponema pallidum antibodies: evidence for sequential development of specific anti-T. pallidum immunoglobulin G responses in patients with early syphilis

Sluis¹,

Reede²,

Boer³

1986

J Clin Microbiol

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The development of immunoglobulin G (IgG) subclass-specific anti-Treponema pallidum antibodies during the course of syphilis in humans was studied with sera from 50 untreated male patients. The patients were divided into five diagnosis groups. In the fluorescent treponemal antibody test, which delineates the presence of cross-reacting antibodies, as well as specific antitreponema antibodies, IgGl, IgG2, and IgG3 subclass antibodies were already present during the seronegative primary stage. Specific antibodies, which were detected by the fluorescent treponemal antibody absorption test, were first present during the serotype-variable primary stage. These antibodies were almost exclusively of the IgGl and IgG3 subclasses. In later stages, antibodies of other subclasses were detectable. Titration of IgGl antitreponema antibodies in three electrophoretically different IgG fractions revealed an asymmetric distribution in these fractions during primary syphilis. The antibodies were largely confined to the most basic fraction during primary syphilis. A sudden change in the distribution was noted between the end of the primary stage and the secondary stage; an even distribution of IgGl antitreponema antibodies existed in the late latent stage. These findings confirm and extend previous results from our laboratory. The development of antibodies detected by both tests is discussed in terms of a sequential stimulation of the immune system due to the presence of an extracellular layer covering the treponemas or, alternatively, in terms of a suppression of the immune response during early syphilis.

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Immunoregulatory properties of serum from patients with different stages of syphilis

Cited by 7 publications

References 11 publications

Treponema pallidum protein Tp47 induced prostaglandin E2 to inhibit the phagocytosis in human macrophages

Treponema pallidum protein Tp47 induced prostaglandin E2 to inhibit the phagocytosis in human macrophages

Serum Regulation of In Vitro Lymphocyte Responses in Early Experimental Syphilis

Immunoglobulin G subclasses of fluorescent anti-Treponema pallidum antibodies: evidence for sequential development of specific anti-T. pallidum immunoglobulin G responses in patients with early syphilis

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