Immunopathogenesis of neurosyphilis: clinical management perspectives

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Abstract

This review provides a comprehensive analysis on the immunopathogenesis of neurosyphilis and discusses the related clinical perspectives. Neurosyphilis remains one of the most complex and variable forms of syphilitic infection, driven by the interaction between T. pallidum and host innate and adaptive immune cells leading to chronic inflammation and damage to the nervous system. The article highlights three major relevant areas. 1) Cellular and molecular mechanisms. The role of different T-lymphocyte subsets, cytokine cascades, macrophages, and microglia in shaping persistent inflammation, disrupting immune control, and contributing to neurodegenerative processes is examined. In particular, it emphasizes the imbalance between pro- and anti-inflammatory cytokines, as well as the strategies by which the pathogen evades immune surveillance. 2) Clinical manifestations and diagnostic approaches. Current knowledge of the wide clinical spectrum of neurosyphilis is summarized, ranging from asymptomatic forms to severe progressive neurological involvement. Special attention is given to biomarkers, including cerebrospinal fluid indices and immunological tests, as well as instrumental methods such as MRI, serological, and molecular assays, which help refine disease staging and assess activity. 3) Therapeutic opportunities and prospective targets. Existing antibiotic regimens are discussed, along with the challenges of limited efficacy and potential antibiotic resistance. The review further explores the potential of immunotherapy and combined strategies aimed at restoring immune control and reducing central nervous system inflammation. Overall, the review integrates fundamental aspects of immunopathogenesis with practical clinical considerations. By linking cellular and molecular insights with diagnostic and therapeutic perspectives, it provides a relevant resource for both clinicians and researchers primarily engaged in the search for innovative therapeutic strategies against neurosyphilis.

About the authors

Vladimir A. Bekhalo

N.F. Gamaleya Federal Research Center for Epidemiology and Microbiology

Author for correspondence.
Email: nearmedic_uc@mail.ru

PhD (Biology), Leading Researcher, Laboratory of Immunity Regulation and Immunological Tolerance

Russian Federation, Moscow

O. K. Loseva

Russian Biotechnological University (ROSBIOTECH)

Email: nearmedic_uc@mail.ru

DSc (Medicine), Professor, Professor of the Department of Skin and Venereal Diseases with a Course in Cosmetology of the Medical Institute of Continuing Education

Russian Federation, Moscow

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