Infiltrate of syphilitic lesions before and after treatment.

Tosca, Androniki; Lehou, J; Hatjivasiliou, M; Varelzidis, A.; Stratigos, J.

doi:10.1136/sti.64.5.289

Cited by 22 publications

(25 citation statements)

References 15 publications

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“…Lesional macrophages appear a few days later, which is paralleled by a sharp decline of lesional spirochetes. 4,19,20 Similarly, T-cells and macrophages are found in human primary chancres 21,22 and secondary lesions. 11,6 In functional studies phagocytosis of opsonized T. pallidum by macrophages, 9,10 activated by IFN-␥, 10 has been demonstrated, and degraded T. pallidum organisms were found in phagocytic vacuoles of macrophages.…”

Section: Discussionmentioning

confidence: 99%

Host Defense Mechanisms in Secondary Syphilitic Lesions

Stary

Klein

Brüggen

et al. 2010

The American Journal of Pathology

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Cell-mediated immunity is thought to be of critical importance in antisyphilitic host defense, but the exact mechanisms are still unknown. This fact is particularly true for HIV-infected persons with a deficit in CD4 ؉ T-cell number. We therefore obtained lesional skin samples from HIV ؉ and HIV ؊ patients with secondary syphilis at different time points of lesional age to search both for causative microorganisms and to characterize the inflammatory infiltrate. By doing so, we detected Treponema pallidum spirochetes with a much greater abundance in late lesions of HIV

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Section: Discussionmentioning

confidence: 99%

Host Defense Mechanisms in Secondary Syphilitic Lesions

Stary

Klein

Brüggen

et al. 2010

The American Journal of Pathology

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“…In human disease, both CD4 ϩ T cells and CD8 ϩ T cells are observed in primary and secondary lesions, although reports indicate that their relative proportions vary (8,18,28,31). Importantly, very little is known about the kinetics of these important T-cell subsets during lesion progression and resolution.…”

Section: Discussionmentioning

confidence: 99%

“…The cell phenotypes and cytokines present in early syphilitic lesions during human infection and experimental infection in the rabbit models suggest that the early immune response to T. pallidum is characteristic of a delayedtype hypersensitivity or Th1 response. A large number of mononuclear cells, consisting mostly of T cells and macrophages, infiltrate early lesions prior to bacterial clearance and lesion healing (15,23,24,28). CD4 ϩ helper T cells are believed to mediate bacterial clearance primarily through the production of cytokines, such as gamma interferon (IFN-␥), which activate macrophages (14, 30).…”

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confidence: 99%

CD4⁺Lymphocytes and Gamma Interferon Predominate in Local Immune Responses in Early Experimental Syphilis

Leader¹,

Godornes

VanVoorhis

et al. 2007

Infect Immun

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The clearance of Treponema pallidum subsp. pallidum from early syphilis lesions involves infiltration of a large number of mononuclear cells and is characteristic of a cell-mediated immune response. In the present study, we sought to determine the relative abundance of different T-lymphocyte populations and Th1/Th2-associated cytokines present in testicular lesions following experimental infection with the Chicago strain of T. pallidum. Using flow cytometry, we examined the proportion of CD4 ؉ and CD8 ؉ T cells present throughout the progression and resolution of primary syphilis in the rabbit model. We related these findings to the results of real-time reverse transcription-PCR quantification of treponemal and cytokine mRNA levels. Treponemal mRNA levels reached peak values on day 18 postinfection, coincident with an initial peak in the level of T cells, which were primarily CD4 ؉ T cells. T-cell levels increased again during resolution of orchitis, and there was an increased proportion of CD8 ؉ T cells. The maximum gamma interferon (IFN-␥) and interleukin-10 (IL-10) mRNA levels were observed on days 11 and 18, respectively, while only negligible amounts of IL-4 and IL-2 were detected throughout the infection. In addition to showing the temporal relationship between treponemal burden and T-cell responses during lesion progression, our results also demonstrate that the composition of the T-cell population changes during lesion resolution. The presence of the mRNA for IFN-␥, but not IL-4, is consistent with cytokine expression in human syphilis and provides further support for the hypothesis that there is a Th1 predominance during the early immune response to T. pallidum.Natural infection with Treponema pallidum subsp. pallidum, the causative agent of syphilis, results in the formation of a primary lesion, or chancre, at the site of infection. A vigorous immune response develops early during infection and results in local clearance of the majority of treponemes and resolution of the primary lesions. The cell phenotypes and cytokines present in early syphilitic lesions during human infection and experimental infection in the rabbit models suggest that the early immune response to T. pallidum is characteristic of a delayedtype hypersensitivity or Th1 response. A large number of mononuclear cells, consisting mostly of T cells and macrophages, infiltrate early lesions prior to bacterial clearance and lesion healing (15,23,24,28). CD4 ϩ helper T cells are believed to mediate bacterial clearance primarily through the production of cytokines, such as gamma interferon (IFN-␥), which activate macrophages (14, 30). Macrophages then engulf and kill opsonized treponemes (2, 17). There is also evidence that activated cytolytic (CD8 ϩ ) T lymphocytes participate in the local immune response within lesions, although their role in clearance remains unclear (18, 31). An important role for antibody in bacterial clearance has also been demonstrated (3, 4, 16); however, reports vary on the relative abundance of B cells within the le...

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“…Similarly, T cells and macrophages are found in rabbit dermal lesions (276), as well as in human primary chancres (90,314,325) and secondary lesions (90,198,325,333 (198). mRNA for the cytokines gamma interferon (IFN-␥) and IL-2, which function to activate macrophages and stimulate proliferation of T cells, respectively, is also found in primary and secondary lesions (323).…”

Section: Immune Clearancementioning

confidence: 99%

Biological Basis for Syphilis

2006

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SUMMARY Syphilis is a chronic sexually transmitted disease caused by Treponema pallidum subsp. pallidum. Clinical manifestations separate the disease into stages; late stages of disease are now uncommon compared to the preantibiotic era. T. pallidum has an unusually small genome and lacks genes that encode many metabolic functions and classical virulence factors. The organism is extremely sensitive to environmental conditions and has not been continuously cultivated in vitro. Nonetheless, T. pallidum is highly infectious and survives for decades in the untreated host. Early syphilis lesions result from the host's immune response to the treponemes. Bacterial clearance and resolution of early lesions results from a delayed hypersensitivity response, although some organisms escape to cause persistent infection. One factor contributing to T. pallidum's chronicity is the paucity of integral outer membrane proteins, rendering intact organisms virtually invisible to the immune system. Antigenic variation of TprK, a putative surface-exposed protein, is likely to contribute to immune evasion. T. pallidum remains exquisitely sensitive to penicillin, but macrolide resistance has recently been identified in a number of geographic regions. The development of a syphilis vaccine, thus far elusive, would have a significant positive impact on global health.

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Infiltrate of syphilitic lesions before and after treatment.

Cited by 22 publications

References 15 publications

Host Defense Mechanisms in Secondary Syphilitic Lesions

Host Defense Mechanisms in Secondary Syphilitic Lesions

CD4⁺Lymphocytes and Gamma Interferon Predominate in Local Immune Responses in Early Experimental Syphilis

Biological Basis for Syphilis

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Infiltrate of syphilitic lesions before and after treatment.

Cited by 22 publications

References 15 publications

Host Defense Mechanisms in Secondary Syphilitic Lesions

Host Defense Mechanisms in Secondary Syphilitic Lesions

CD4+Lymphocytes and Gamma Interferon Predominate in Local Immune Responses in Early Experimental Syphilis

Biological Basis for Syphilis

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CD4⁺Lymphocytes and Gamma Interferon Predominate in Local Immune Responses in Early Experimental Syphilis