Russian Journal of Infection and ImmunityRussian Journal of Infection and ImmunityИнфекция и иммунитет2220-76192313-7398SPb RAACI1803010.15789/2220-7619-ION-18030REVIEWSОБЗОРЫReview ArticleImmunopathogenesis of neurosyphilis: clinical management perspectivesИммунопатогенез нейросифилиса: возможности для клинического веденияBekhaloVladimir A.БехалоВладимир Андреевич
Russian Federation

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

к.б.н., ведущий научный сотрудник лаборатории регуляции иммунитета и иммунологической толерантности

nearmedic_uc@mail.ruLosevaO. K.ЛосеваО. К.
Russian Federation

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

д.м.н., профессор, профессор кафедры кожных и венерических болезней с курсом косметологии Медицинского института непрерывного образования

nearmedic_uc@mail.ruN.F. Gamaleya Federal Research Center for Epidemiology and MicrobiologyФГБУ Национальный исследовательский центр эпидемиологии и микробиологии им. Н.Ф. Гамалеи Минздрава РоссииRussian Biotechnological University (ROSBIOTECH)ФГБОУ ВО Российский биотехнологический университет (РОСБИОТЕХ)2710202524122025156103510483009202522102025Copyright ©; 2025, Bekhalo V.A., Loseva O.K.Copyright ©; 2025, Бехало В.А., Лосева О.К.2025Bekhalo V.A., Loseva O.K.Бехало В.А., Лосева О.К.https://creativecommons.org/licenses/by/4.0https://iimmun.ru/iimm/article/view/18030

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.

Обзор посвящен всестороннему анализу иммунопатогенеза нейросифилиса и рассмотрению клинических перспектив, связанных с данной проблемой. Нейросифилис остается одной из наиболее сложных и вариабельных форм сифилитической инфекции, в основе которой лежит взаимодействие T. pallidum с клетками врожденного и адаптивного иммунитета, приводящее к хроническому воспалению и повреждению нервной системы. В работе выделены три ключевых направления анализа. 1) Клеточные и молекулярные механизмы: рассматривается роль Т-лимфоцитов различных субпопуляций, цитокиновых каскадов, макрофагов и микроглии в формировании персистирующего воспаления, нарушении иммунного контроля и развитии нейродегенеративных процессов; подчеркивается значимость дисбаланса про- и противовоспалительных цитокинов, а также феномена уклонения возбудителя от иммунного ответа. 2) Клинические проявления и диагностические подходы: обобщены современные представления о спектре симптоматики нейросифилиса — от асимптомных форм до тяжелых прогрессирующих поражений нервной системы; особое внимание уделено использованию биомаркеров, включая ликворные показатели и иммунологические тесты, а также инструментальным методам (МРТ, серологическим и молекулярным исследованиям), которые позволяют уточнять стадию и активность процесса. 3) Терапевтические возможности и перспективные мишени: обсуждаются существующие схемы антибиотикотерапии, проблемы недостаточной эффективности и возможной антибиотикорезистентности; анализируется потенциал иммунотерапии и комбинированных подходов, направленных на восстановление иммунного контроля и ограничение воспаления в центральной нервной системе. Таким образом, обзор сочетает фундаментальные аспекты иммунопатогенеза с практическими клиническими задачами. Он позволяет интегрировать новые данные о клеточных и молекулярных механизмах инфекции в контекст диагностики и лечения, что делает материал актуальным как для клиницистов, так и для исследователей, занимающихся поиском новых терапевтических стратегий.

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