SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Partial protection against cutaneous syphilis and dissemination of treponemes to the regional lymph nodes was achievable in Treponema pallidum-infected neonatal strain 2 guinea pigs having syphilis-immune mothers. This evidence for enhanced resistance was associated with the natural transfer of antitreponemal, maternally derived immunoglobulins before parturition.
Explore the source record for details and available documents.
Immunofluorescent examination of formalin-fixed tissue for Treponema pallidum has generally been unsatisfactory because of nonspecific background fluorescence and poor contrast. We examined the process of treating deparaffinized formalin-fixed tissue sections with 1% ammonium hydroxide (NH4OH) to improve fluorescent staining. Treponema pallidum- and Treponema pertenue-infected rabbit testes or human tissue biopsy specimens fixed in 10% buffered formalin and embedded in paraffin were examined. Sections were cut one week to five years after embedment. Tissues were then stained with fluorescein- or rhodamine-labeled human anti- T pallidum globulin for 30 minutes at 37 degrees C. Treponemes were consistently stained and background staining was generally reduced after NH4OH treatment in both fresh and stored tissue. Cutting sections at a thickness of approximately 2 micron was critical to achieve optimal fluorescence.
The role of complement in humoral-mediated resistance to frambesial infection (yaws) needs to be defined. The level of serum C3 was reduced shortly after infection of hamsters with Treponema pallidum subspecies pertenue. Five weeks after frambesial infection, the serum C3 level began to increase and by week 7 no difference was detected between infected and uninfected hamsters. When C3 was depleted in hamsters by injection of 20 units of cobra venom factor (CoVF), two alterations in host resistance to frambesial infection occurred. Depletion of C3 abrogated the ability of immune serum to confer complete protection on normal hamsters against infection with the yaws spirochete. In all hamsters receiving immune serum but not CoVF, lesions failed to develop and lymph nodes weighed significantly less (P less than or equal to 0.1) than those of controls. Furthermore, no treponemes were detected in the lymph nodes of passively immunized animals. Second, depletion of C3 increased the susceptibility of hamsters to frambesial infection. The onset and progression of frambesial lesions were enhanced as compared with frambesial-infected hamsters not treated with CoVF. Finally, CoVF treatment did not reduce the ability of frambesia-immune hamsters cured of disease with penicillin to resist reinfection. These results demonstrate that complement influences the pathogenesis of yaws.
Explore the source record for details and available documents.
Treponema pallidum, its membrane lipoproteins, and synthetic lipoprotein analogues (lipopeptides) were each examined to determine whether they induced CCR5 expression on human peripheral blood mononuclear cells (PBMC). Reverse transcription-polymerase chain reaction for CCR5 gene transcripts, macrophage inflammatory protein (MIP)-1beta binding assays, and flow cytometry revealed that either T. pallidum, a representative treponemal lipoprotein, or a corresponding synthetic lipopeptide induced CCR5 on CD14 monocytes but not on CD3 lymphocytes. CXCR4, the coreceptor for T cell-tropic strains of human immunodeficiency virus type 1 (HIV-1), was not induced on PBMC by treponemes or by lipoproteins or lipopeptides. Consistent with these findings, T. pallidum, lipoprotein, and synthetic lipopeptide all promoted the entry of a macrophage-tropic, but not a T cell-tropic, strain of HIV-1 into monocytes. These combined results imply that T. pallidum and its constituent lipoproteins likely induce the expression of CCR5 on macrophages in syphilitic lesions, thereby enhancing transmission of macrophage-tropic HIV-1.
Immunoblotting techniques were used to examine the proteins of Treponema pallidum recognized by IgM and IgG antibodies in sera from infants with congenital syphilis and their mothers. Infected infants' serum IgM reactivity to treponemal antigens differed from that of control infants born to normal, serofast, and biologic false-positive mothers. Each of the infected infants' sera exhibited IgM reactions to the 47- and 37-kilodalton (kDa) proteins of T. pallidum. Although rheumatoid factor was detected in the sera of half of the infected infants, removing this factor did not alter the pattern of IgM blots. IgG reactions in infants were almost exclusively of the IgG1 and IgG3 subclasses and mirrored those of the mother, except for IgG1 and IgG3 reactions to the 83-kDa treponemal protein, which were unique to infants' sera. Our results suggest that the findings of IgM antibody directed against the 47- or 37-kDa antigens of T. pallidum may help to diagnose congenital syphilis at birth.
An in vivo animal model was used to assess the enteropathogenicity of the etiological agent (Treponema hyodysenteriae) of swine dysentery. Multiple ligated ileal loops, prepared in New Zealand white rabbits, were challenged with either pathogenic (B78 and B204) or nonpathogenic (Pu) isolates of the organism. The pathogenic isolates induced the onset of intestinal fluid accumulation as early as 4 h, with maximal fluid induction at 18 h postchallenge. Gross lesions of the intestinal mucosa, observed in ileal loops of rabbits sacrificed 24 h postchallenge, were characteristic of swine dysentery. Both pathogenic isolates colonized the epithelial surface and eroded the mucosal barrier, as determined by histological and scanning electron microscopic observations. Intestinal fluid accumulation and erosion of the mucosal barrier were not observed in ileal loops exposed to the nonpathogenic isolate (Pu) or to either of the nonviable pathogenic (B78 and B204) isolates. The ability of pathogenic isolates to initiate and produce infection in rabbit ligated ileal loops, which closely resembles the disease in swine, provides a system with which to study experimental swine dysentery.
Hamsters infected intradermally with Treponema pallidum Bosnia A develop extensive chronic skin lesions, usually accompanied by metastatic lesions involving the paws, lips, and anal region and by lymph nodes teeming with treponemes. Throughout the course of syphilitic infection, cells from the inguinal lymph nodes responded poorly to stimulation with suboptimal, optimal, or supraoptimal concentrations of concanavalin A, phytohemagglutinin P, or lipopolysaccharide. The response of syphilitic spleen cells was variable. Depression of lymphocyte reactivity to mitogens preceded clinical signs of infection and correlated well with the chronicity of syphilitic infection. When syphilitic hamsters were treated with a curative dose of penicillin, their mitogenic responses returned to normal or were slightly elevated. No correlation existed between mitogenic activity and the ability of lymphoid cells to induce an effective immune response when transferred to normal recipients. No significant differences in protection were detected among recipients of immune cells with or without activity to mitogens. These results demonstrate that lymphocyte transformation by mitogens in vitro is not a measure of effective treponemicidal activity and so may not be a valid indicator of the protective immune status of syphilitic animals.
Superinfection of human immunodeficiency virus (HIV)-1-infected rabbits with Treponema pallidum, Mycobacterium avium, herpes simplex, Candida albicans, Mycoplama incognitus, and malignant catarrhal fever virus, as well as irradiation or cortisone treatment, fails to activate production of infectious virus. For up to 6 months after infection of rabbits with HIV-infected cells or free virus, there are neither clinical symptoms nor positive laboratory tests for detection of HIV. However, after superinfection with other agents, HIV sequences may be transiently found in peripheral blood mononuclear cells by polymerase chain reaction (PCR), and multiple antibodies to HIV antigens may be detected by Western blotting. Both the PCR positivity and Western blot reactivity become negative with time after superinfection. Other than delayed healing of the skin lesions produced by T. pallidum and vaccinia in HIV-infected rabbits, there is no evidence of any immune abnormality. After death, gag sequences are detectable in the splenocytes of essentially every HIV-infected rabbit, and the splenocytes of eight of 25 infected rabbits responded by proliferation to HIV peptides. In addition, gag sequences are detectable in rabbits that are injected with lymphoid cells from HIV-infected rabbits. However, after multiple testing of both peripheral blood of living rabbits and organs of rabbits that died or were killed (spleen, brain, lymph nodes, liver, and gastrointestinal tract), no viable virus has ever been convincingly detected by in vitro cultivation with indicator cells. In contrast to some other published reports, these data indicate that HIV-1 infection of rabbits does not provide a model for AIDS pathogenesis therapy or prevention, but it may be useful as a model to study the relative resistance of a small fraction of the human population to development of AIDS after HIV infection.
One hundred years after the discovery of the infectious agent of syphilis and implementation of the first serological test for the diagnosis of syphilis, important progress in the evaluation of host immune response against Treponema (T.) pallidum infection has been made. The paper focuses on the new modifications of non-treponemal tests (the use of synthetic cardiolipin and lecithin in Venereal Disease Research Laboratory--VDRL test and the application of the VDRL antigen to immunoenzymatic assays) as well as of treponemal tests. Original treponemal antigens are replaced by recombinant and synthetic antigens (TpN44,5- TmpA, TpN15, TpN17 and TpN47) and by antigens obtained after sequencing of the complete T. pallidum genome (Tp0453, Tp0257 and Tp92) in modifications of immunoenzymatic assays. The new diagnostic strategy, namely the examination of the number of cells producing T. pallidum specific antibodies is also presented. Despite the progress achieved in studies on humoral response in syphilis during last years, the practical application of new tests in diagnosis of the infection requires further studies.
The antitreponemal activity of trospectomycin (a novel 6'-propyl analog of spectinomycin) was correlated with concentrations in serum and tissue chamber fluid in a cutaneously-infected rabbit model of syphilis. After single-dose intramuscular (im) injections of trospectomycin, spectinomycin hydrochloride, and aqueous procaine penicillin G(APPG), concentrations of the drugs in paired specimens of serum and tissue fluid were determined and correlated with response of Treponema pallidum-infected lesions. Lesions responded most rapidly in APPG-treated animals. Rapid response correlated with more prolonged levels of APPG in both serum and tissue fluid. Trospectomycin, when given in single doses exceeding 40 mg/kg, surpassed penicillin in peak serum levels (greater than 60 micrograms/ml at 1 hr) but not in duration of activity. Higher and prolonged concentrations of trospectomycin in tissue fluid correlated with more effective clearance of treponemes from cutaneous lesions. Animals treated with less than 40 mg of trospectomycin/kg or with 20-80 mg/kg of the parent compound (spectinomycin hydrochloride) had cutaneous lesions that were persistently darkfield-positive, as confirmed by three or more consecutive smears.
Due to uncharacteristic symptoms of central nervous system (CNS) alterations during Treponema pallidum (TP) infection, the exact diagnosis of neurosyphilis has become more and more difficult. Particularly, there is a lack of sufficiently specific and sensitive assays for the demonstration of intrathecal synthesis of TP-specific immunoglobulins. TP-specific IgG or IgM class antibodies were estimated quantitatively in serum and cerebrospinal fluid (CSF) of 302 syphilitic patients by a modified enzyme immunoassay (ELISA), and antibody concentrations were quantitated as ELISA units per mg total IgG or IgM. In 197 of 237 patients with neurosyphilis an intrathecal synthesis of TP-specific IgG or IgM could be demonstrated by a 3- to 450-fold higher antibody concentration in the CSF than in the corresponding serum. In contrast, 65 patients without CNS involvement on the infection did not show any difference in the antibody concentration of CSF and serum. Thus, the diagnosis of neurosyphilis respectively the exclusion of CNS participation on the TP infection on an immunological base has become possible.
Normal piglets kept at 16 degrees C. and gnotobiotic piglets kept at 32 degrees C. rapidly destroyed Treponema pallidum, while gnotobiotic piglets kept at 26 degrees C. showed slightly slower clearance. No infections were established. The high body temperature of the piglets has an important influence on the survival of T. pallidum.
Syphilis is a chronic sexually transmitted infection caused by Treponema pallidum subspecies pallidum. Its protean clinical presentations earned it the name of the 'Great Mimicker'. Understanding of disease pathogenesis and how host-pathogen interactions influence the course of disease have been compromised by the facts that the organism cannot be grown in vitro and, as an exclusively human pathogen, inferences made from animal models are of limited applicability. Many questions remain about how T. pallidum biology contributes to distinctive features of syphilis, such as its ability to persist in the presence of a brisk host response or its propensity for neuro-invasion and congenital transmission. In 1998, the genome of T. pallidum was sequenced. The organism has a relatively small genome, suggesting that it utilizes host biosynthesis to fulfil some of its metabolic needs. While biological functions are suggested for only about 55% of T. pallidum's 1041 open reading frames, even these relatively early studies offer important insights into syphilis pathogenesis. A family of repeat genes, the Tp genes, encode proteins homologous to the major sheath proteins of T. denticola. Antibodies to the TprK variable regions are protective in a rabbit model. With successive passage, increasing diversity is observed in the TprK V region genes. Antigenic variation through gene conversion has been hypothesized to be one mechanism of escaping immune surveillance, allowing for prolonged infection and persistence in the presence of a robust host response. Human and animal studies suggest that a Th1 response is elicited in primary syphilis. Progression to the secondary stage is accompanied by a shift to a Th2 response, allowing for incomplete clearance of the pathogen. In pregnancy, intense inflammatory responses and prostaglandins induced by fetal infection may be responsible for fetal death or pre-term delivery and severe growth retardation or other manifestations of congenital syphilis. Understanding of the molecular targets of these immune responses may facilitate the development of vaccines for syphilis.
Ticks were screened for spirochetes and serum samples from white-tailed deer (Odocoileus virginianus) were assayed for antibodies to Borrelia burgdorferi during 1983-1984. Using fluorescein isothiocyanate-labeled rabbit antibodies produced to B. burgdorferi, the etiologic agent of Lyme disease, spirochetes were detected in Ixodes dammini (10.5% of 1,193) and Dermacentor albipictus (0.6% of 157) adults from Connecticut, I. dammini nymphs (49.1% of 108) and adults (64.7% of 99) from Armonk, New York, and in I. scapularis (0.4% of 531) and Amblyomma americanum (3.5% of 173) adults from North Carolina. Infected ticks were either seeking hosts or feeding on deer during the summer and fall. Direct fluorescent antibody staining also revealed spirochetes in two larvae of I. scapularis that emerged from eggs deposited by separate females in the laboratory. Using indirect immunofluorescence tests, antibodies to B. burgdorferi were identified in white-tailed deer living in tick-infested areas of all three states. Aside from minor cross-reactivity, there was no serologic evidence of Treponema or Leptospira infections. Ixodes dammini is a primary vector of B. burgdorferi in northeastern United States, but in North Carolina, other ixodid ticks may transmit this spirochete to humans and wildlife.
BACKGROUND AND OBJECTIVES: The authors have previously shown that complement-dependent treponemicidal antibody measured by the "washed-killing" assay is directed exclusively against surface-exposed targets on Treponema pallidum, presumably the Treponema pallidum rare outer membrane proteins detected by freeze-fracture electron microscopy. GOAL OF THIS STUDY: Because immune mechanisms against Treponema pallidum rare outer membrane proteins are likely to be central to a protective host response, it was examined whether a relationship could be established between treponemicidal levels as measured by the "washed-killing" assay and host immunity in experimental syphilis. STUDY DESIGN: Three groups of Treponema pallidum-infected rabbits were treated curatively with penicillin at 9 days, 30 days, and 6 months post-infection to generate animals with varying degrees of immunity to challenge re-infection. The level of complement-dependent treponemicidal activity in sera obtained before infection (basal) and before intradermal challenge was determined by the "washed-killing" assay and compared with that detected using conventional in vitro immobilization. RESULTS: Using the "washed-killing" assay, a close quantitative correlation as measured by a treponemal immobilizing endpoint titer was demonstrable between prechallenge treponemicidal antibody and the status of immunity to re-infection. Sera from rabbits completely susceptible to symptomatic and disseminated asymptomatic re-infection lacked treponemicidal antibody. Sera from challenged rabbits with a relatively low degree of immunity to symptomatic disease showed endpoints of < or = 4. Rabbits with a relatively high degree of immunity to symptomatic reinfection and resistant to disseminated disease had endpoints that ranged from 6 to 96. Rabbits completely resistant to challenge exhibited endpoints ranging from 96 to 128. CONCLUSION: Treponemicidal antibody measured by the "washed-killing" assay correlated closely with the status of immunity in experimental rabbit syphilis. Thus, antibody measured by this assay may be directed against key protective Treponema pallidum surface immunogens.
Immune regulation during syphilitic infection is extremely complex. This paper presents findings on the early events of T-cell activation following testicular infection in rabbits. Treponema pallidum was preincubated for 24 h with nonadherent spleen cells. After being washed to remove the organisms, these spleen cells were either stimulated with concanavalin A (ConA) to induce interleukin-2 (IL-2), or added to adherent cells that were then stimulated with lipopolysaccharide to induce IL-1. Preincubation with the treponemes up-regulated nonadherent cell functions. These sensitized cells increased their IL-2 production and augmented macrophage IL-1 synthesis. In sharp contrast, if this preincubation step was omitted, down-regulation was apparent. When T. pallidum was directly incubated with nonadherent cells in the presence of ConA, reduced levels of IL-2 were detected. Nonadherent cells from infected rabbits secreted soluble suppressive factors after 48 h of in vitro incubation; these factors inhibited ConA-induced IL-2 generation as well as ConA-induced lymphocyte proliferation. At least some of this suppressive activity was attributed to transforming growth factor. In addition, when T lymphocytes were depleted, less suppression was detected. Treponemes also inhibited ConA-induced T-cell proliferation, and monophosphoryl lipid A reversed this inhibitory effect. Since monophosphoryl lipid A neutralizes T-suppressor activity, these findings further suggest a role for T-suppressor activity during syphilitic infection. Finally, T. pallidum directly stimulated IL-2 synthesis when coincubated with phorbol myristate acetate. This agent reverses the prostaglandin E2 blockage of T-helper cell protein kinase C, a necessary second messenger signal for IL-2 synthesis. In summary, T-cell functions are extremely complex and represent a composite of both stimulation and down-regulation, which occur concurrently but to different degrees.