Host Defense Mechanisms in Secondary Syphilitic Lesions

Stary, Georg; Klein, Irene; Brüggen, Marie‐Charlotte; Kohlhofer, Sabine; Brunner, Patrick M.; Spazierer, Daniel; Müllauer, Leonhard; Petzelbauer, Peter; Stingl, Georg

doi:10.2353/ajpath.2010.100277

Cited by 45 publications

(35 citation statements)

References 44 publications

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“…Previous studies reported an increase of IL-17 in secondary syphilitic lesion and peripheral blood [13], [14]. Recently, Pastuszczak et al also showed elevated CSF IL-17 levels in early asymptomatic neurosyphilis [15], suggesting that IL-17 may be involved in local immune response to T. pallidum infection.…”

Section: Introductionmentioning

confidence: 93%

Increased Interleukin-17 in Peripheral Blood and Cerebrospinal Fluid of Neurosyphilis Patients

et al. 2014

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Background Treponema pallidum infection evokes vigorous immune responses, resulting in tissue damage. Several studies have demonstrated that IL-17 may be involved in the pathogenesis of syphilis. However, the role of Th17 response in neurosyphilis remains unclear.Methodology/Principal FindingsIn this study, Th17 in peripheral blood from 103 neurosyphilis patients, 69 syphilis patients without neurological involvement, and 70 healthy donors were analyzed by flow cytometry. The level of IL-17 in cerebrospinal fluid (CSF) was quantified by ELISA. One-year follow up for 44 neurosyphilis patients was further monitored to investigate the role of Th17/IL-17 in neurosyphilis. We found that the frequency of Th17 cells was significantly increased in peripheral blood of patients with neurosyphilis, in comparison to healthy donors. IL-17 in CSF were detected from 55.3% neurosyphilis patients (in average of 2.29 (0–59.83) pg/ml), especially in those with symptomatic neurosyphilis (61.9%). CSF IL-17 was predominantly derived from Th17 cells in neurosyphilis patients. Levels of IL-17 in CSF of neurosyphilis patients were positively associated with total CSF protein levels and CSF VDRL (Venereal Disease Research Laboratory) titers. Notably, neurosyphilis patients with undetectable CSF IL-17 were more likely to confer to CSF VDRL negative after treatment.ConclusionsThese findings indicate that Th17 response may be involved in central nervous system damage and associated with clinical symptoms in neurosyphilis patients. Th17/IL-17 may be used as an alternative surrogate marker for assessing the efficacy of clinical treatment of neurosyphilis patients.

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Section: Introductionmentioning

confidence: 93%

Increased Interleukin-17 in Peripheral Blood and Cerebrospinal Fluid of Neurosyphilis Patients

et al. 2014

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“…4C,D), liberating lipopeptides and other PAMPs for binding to Toll-like receptors lining the interior of the phagosome and antigenic peptides for presentation to locally recruited T cells 62,104,105 . Activated lesional T cells secrete IFN-γ, promoting clearance by macrophages, but also bolstering the production of tissue-damaging cytokines, such as tumor necrosis factor (TNF) and IL-6 10,106,107 . Immunohistochemical analysis has identified CD4+ and CD8+ T cells 10,106,108,109 , natural killer cells 10 and activated macrophages in early syphilis lesions 10,109 .…”

Section: Mechanisms/pathophysiologymentioning

confidence: 99%

“…Activated lesional T cells secrete IFN-γ, promoting clearance by macrophages, but also bolstering the production of tissue-damaging cytokines, such as tumor necrosis factor (TNF) and IL-6 10,106,107 . Immunohistochemical analysis has identified CD4+ and CD8+ T cells 10,106,108,109 , natural killer cells 10 and activated macrophages in early syphilis lesions 10,109 . Perivascular infiltration of lymphocytes, histiocytes (phagocytic cells in connective tissues) and plasma cells with endothelial cell swelling and proliferation are characteristic histopathological findings in all stages of syphilis and can progress to frank endarteritis obliterans (leading to occlusion of arteries and severe clinical manifestations, such as the stroke syndromes of meningovascular syphilis) 9,110 .…”

Section: Mechanisms/pathophysiologymentioning

confidence: 99%

Syphilis

Peeling

Mabey

Kamb

et al. 2017

Nat Rev Dis Primers

493

387

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Treponema pallidum subspecies pallidum (T. pallidum) causes syphilis via sexual exposure or vertical transmission during pregnancy. T. pallidum is renowned for its invasiveness and immune-evasiveness; its clinical manifestations result from local inflammatory responses to replicating spirochetes and often imitate those of other diseases. The spirochete has a long latent period during which patients have no signs or symptoms, but can remain infectious. Despite the availability of simple diagnostic tests and the effectiveness of treatment with a single dose of long-acting penicillin, syphilis is re-emerging as a global public health problem, particularly among men who have sex with men (MSM) in high-income and middle-income countries. Syphilis also causes several hundred thousand stillbirths and neonatal deaths every year in developing nations. Although several low-income countries have achieved WHO targets for the elimination of congenital syphilis, an alarming increase of syphilis in HIV-infected MSM serves as a strong reminder of the tenacity of T. pallidum as a pathogen. Strong advocacy and community involvement is needed to ensure that syphilis is given high priority on the global health agenda. More investment in research is needed on the interaction between HIV and syphilis in MSM, as well as into improved diagnostics, a better test of cure, intensified public health measures and, ultimately, a vaccine.

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“…This phenomenon could be due to a combination of the role of pathogenic virulence factors, such as tprK gene conversion [11] and/or strong, broadly-reactive oposonophagocytic antibodies in concert with effective CD8 + Th1-mediated adaptive immune responses that may hold the pathogen at bay [12]. Rabbit models of syphilis showed 20% of the animals never developed secondary syphilis in the presence of strong treponemal antibody levels to recombinant p47 antigen as well as VDRL titres similar to those seen in secondary syphilis [11].…”

Section: Discussionmentioning

confidence: 99%