Background Syphilis, a sexually transmitted disease caused by spirochetal bacterium Treponema pallidum, can progress to affect central nervous system, causing neurosyphilis. While many neurosyphilis patients may be asymptomatic, some patients can develop severe neurological and psychiatric symptoms. Accumulating evidence suggest that skin lesions and clinical symptoms of early syphilis patients result from host immune and inflammatory responses. However, very little is known about the immune components in neurosyphilis.

Methodology/Principal Findings In the present study, we perform a comprehensive and comparative analysis of regulatory T cells (Tregs) between 102 neurosyphilis patients and 431 syphilis patients without neurological involvement. We found secondary and serofast patients had increased Treg percentage, suppressive function and TGF-β levels in peripheral blood compared to healthy donors and serum Rapid Plasma Reagin (RPR) titers were positively correlated with Treg numbers in these patients. Neurosyphilis patients had higher Treg frequency in peripheral blood than those of syphilis patients without neurological involvement. Importantly, CD4+ T cells were increased and predominated in cerebrospinal fluid (CSF) of both asymptomatic and symptomatic neurosyphilis patients. Interestingly, a significant decrease in CSF CD4+ CD25 high Treg percentage was observed in symptomatic neurosyphilis patients compared to those of asymptomatic neurosyphilis patients, which may be associated with low CSF TGF-β levels.

Conclusions Our findings suggest that neurological progression in syphilis patients may be associated with an enhanced systemic Treg response and an increased local CD4+ T cell infiltration. A decrease in Treg frequency in CSF of symptomatic neurosyphilis patients indicates that immune-mediate tissue damage might be involved in the development of neurological symptoms.