Serial ultrathin sectioning demonstrating the intracellularity of T. Pallidum. An electron microscopic study.

Lauderdale, V; Goldman, John N.

doi:10.1136/sti.48.2.87

Cited by 32 publications

(26 citation statements)

References 8 publications

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“…2. These organisms appear identical in appearance and dimensions to organisms of the pathogenic Nichols strain of T. pallidum seen in the rabbit testes as described by Sykes andMiller (1971, 1973) and Lauderdale and Goldman (1972).…”

Section: Resultssupporting

confidence: 71%

Treponema pallidum within cells of a primary chancre from a human female.

Sykes¹,

Miller²,

Kalan³

1974

Sexually Transmitted Infections

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Section: Resultssupporting

confidence: 71%

Treponema pallidum within cells of a primary chancre from a human female.

Sykes¹,

Miller²,

Kalan³

1974

Sexually Transmitted Infections

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“…Another possibility is that later during infection a greater number of treponemes reside intracellularly and enter the class I pathway through this route. While T. pallidum is generally considered to be an extracellular pathogen, evidence obtained from microscopic evaluations has suggested that some T. pallidum cells are present inside cells in early lesions (13,25,26). Activated CD8 ϩ T cells within a lesion could contribute to the pool of IFN-␥ available for macrophage activation or could lyse cells containing intracellular treponemes.…”

Section: Discussionmentioning

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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“…From our studies it could not be determined whether the cystic structures seen after 96 h of incubation with antibiotics were able to survive. Gemmae of Treponema pallidum can, for example, be seen intracellularly in the macrophages of rabbits with experimental syphilis half a year after penicillin therapy as well as in human chancre tissue (19,25). Spirochetal gemmae are known to occur in tick midguts, arising on solid culture medium (4,18), and also develop under stress conditions like penicillin treatment (2,3,6,7,25).…”

Section: Discussionmentioning

confidence: 99%

Effects of penicillin, ceftriaxone, and doxycycline on morphology of Borrelia burgdorferi

Kersten

Poitschek

Rauch

et al. 1995

Antimicrob Agents Chemother

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Antibiotic therapy with penicillin, doxycycline, and ceftriaxone has proven to be effective for the treatment of Lyme borreliosis. In some patients, however, it was noticed that borreliae can survive in the tissues in spite of seemingly adequate therapy. For a better understanding of this phenomenon, we investigated the different modes of degeneration of Borrelia burgdorferi suspensions during a 96-h exposure to various antibiotics. By dark-field microscopy and ultrastructural investigations, increasing blebbing and the gradual formation of granular and cystic structures could be followed during the exposure time. Although antibiotic concentrations at the MIC at which 90% of organisms are inhibited after 72 h were 80% or even greater, motile organisms were still present after incubation with penicillin and doxycycline but not after incubation with ceftriaxone. By transmission electron microscopy, intact spirochetal parts, mostly situated in cysts, were seen up to 96 h after exposure with all three antibiotics tested. According to experiences from studies with other spirochetes it is suggested that encysted borreliae, granules, and the remaining blebs might be responsible for the ongoing antigenic stimulus leading to complaints of chronic Lyme borreliosis.Borrelia burgdorferi, the pathogenic agent of Lyme borreliosis, has been recognized as a bacterium that is susceptible to antibiotics. The long-term persistence of these bacteria in tissues, despite adequate treatment of infected patients, has been indicated to be responsible for late complications and a chronic course of disease (17,26,28). The withdrawal of borreliae, or parts of them, into privileged or secluded sites, where they are further inaccessible to antibiotics, raises the question of whether antibiotics themselves can be made responsible for transforming the organism into a persistent, viable, or nonviable but antigenically potent form.Immobilization of bacteria has been seen as a result of incubation with antibiotics in vitro (21). By light microscopy, Preac-Mursic et al. (29) observed blebs, spherical structures, and granules in B. burgdorferi cultures during incubation with antibiotics. In ultrastrucutral studies the action of penicillin on cultures of Borrelia hermsii has been investigated (3).Penicillin, doxycycline, and ceftriaxone are the most preferred antibiotics for treating Lyme borreliosis. Although certain differences in the actions of these antimicrobial agents have been evaluated, they seem to be equally effective (34).Culture experiments were carried out to investigate the actions of these antibiotics on the motility, morphology, and survival of B. burgdorferi during exposure to antibiotic solutions. The course and mode of degeneration of these spirochetes were recorded on a videomicroscope and were photographed with an electron microscope. MATERIALS AND METHODSCulture experiments. Three strains of B. burgdorferi sensu lato, B31 (ATCC 35219) and two isolates from erythema migrans lesions on the skin of patients in Vienna, isolates hig...

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Serial ultrathin sectioning demonstrating the intracellularity of T. Pallidum. An electron microscopic study.

Cited by 32 publications

References 8 publications

Treponema pallidum within cells of a primary chancre from a human female.

Treponema pallidum within cells of a primary chancre from a human female.

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

Effects of penicillin, ceftriaxone, and doxycycline on morphology of Borrelia burgdorferi

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Serial ultrathin sectioning demonstrating the intracellularity of T. Pallidum. An electron microscopic study.

Cited by 32 publications

References 8 publications

Treponema pallidum within cells of a primary chancre from a human female.

Treponema pallidum within cells of a primary chancre from a human female.

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

Effects of penicillin, ceftriaxone, and doxycycline on morphology of Borrelia burgdorferi

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