Abstract
BackgroundSyphilis, a sexually transmitted disease caused by spirochetal bacterium Treponema pallidum, can progress to affect the central nervous system, causing neurosyphilis. Accumulating evidence suggest that regulatory T cells (Tregs) may play an important role in the pathogenesis of syphilis. However, little is known about Treg response in neurosyphilis.Methodology/Principal FindingsWe analyzed Treg frequencies and Transforming Growth Factor-β (TGF-β) levels in the blood and CSF of 431 syphilis patients without neurological involvement, 100 neurosyphilis patients and 100 healthy donors. Suppressive function of Tregs in peripheral blood was also assessed. Among syphilis patients without neurological involvement, we found that secondary and serofast patients had increased Treg percentages, suppressive function and TGF-β levels in peripheral blood compared to healthy donors. Serum Rapid Plasma Reagin (RPR) titers were positively correlated with Treg numbers in these patients. Compared to these syphilis patients without neurological involvement, neurosyphilis patients had higher Treg frequency in peripheral blood. In the central nervous system, neurosyphilis patients had higher numbers of leukocytes in CSF compared to syphilis patients without neurological involvement. CD4+ T cells were the predominant cell type in the inflammatory infiltrates in CSF of neurosyphilis patients. Interestingly, among these neurosyphilis patients, a significant decrease in CSF CD4+ CD25high Treg percentage and number was observed in symptomatic neurosyphilis patients compared to those of asymptomatic neurosyphilis patients, which may be associated with low CSF TGF-β levels.ConclusionsOur findings suggest that Tregs might play an important role in both bacterial persistence and neurologic compromise in the pathogenesis of syphilis.
Highlights
China has experienced an expanding epidemic of syphilis infection in the last 10 years [1,2]
Our findings suggest that Tregs might play an important role in both bacterial persistence and neurologic compromise in the pathogenesis of syphilis
Treg Percentages Are Elevated in the Peripheral Blood of Primary, Secondary, Latent and Serofast Syphilis Patients Human Tregs were identified as CD4+CD25high or
Summary
China has experienced an expanding epidemic of syphilis infection in the last 10 years [1,2]. In 2011, the national incidence rate was 32.04 per 100,000 population and 429,677 new cases were reported [3] This sexually transmitted disease has reemerged as a significant public health issue in China due to its serious, irreversible sequelae [4] and its strong association with HIV infection [5]. Several studies have demonstrated that T. pallidum may actively harness host immune suppression mechanisms to facilitate persistence and dissemination [18,19]. A recent study has demonstrated that T. pallidum antigen TpF1 could promote development of regulatory T cells (Tregs) in the patients with secondary syphilis [18]. Tregs represent a unique population of CD4+ T cells with potent immune suppressive activity [20,21].
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