Russian Journal of Infection and ImmunityRussian Journal of Infection and ImmunityИнфекция и иммунитет2220-76192313-7398SPb RAACI1788010.15789/2220-7619-EPO-17880REVIEWSОБЗОРЫReview ArticleEarly phases of tuberculosis infection: immune response and host genetic controlРанние фазы туберкулезной инфекции: иммунный ответ и генетический контроль хозяинаKondratievaTatiana K.КондратьеваТатьяна Константиновна
Russian Federation

DSc (Biology), Leading Researcher, Laboratory of Immunogenetics, Immunology Department

д.б.н., ведущий научный сотрудник лаборатории иммуногенетики отдела иммунологии

tanya.kondratieva.47@mail.ruKondratievaElena V.КондратьеваЕлена Валерьевна
Russian Federation

PhD (Biology), Senior Researcher, Laboratory of Immunogenetics, Immunology Department

к.б.н., старший научный сотрудник лаборатории иммуногенетики отдела иммунологии

alyonakondratyeva74@gmail.comAptAlexander S.АптАлександр Соломонович
Russian Federation

DSc (Biology), Professor, Head of the Laboratory of Immunogenetics, Immunology Department

д.б.н., профессор, зав. лабораторией иммуногенетики отдела иммунологии

alexapt0151@gmail.comCentral TB Research InstituteФГБНУ Центральный научно-исследовательский институт туберкулеза07042025150920251534314450303202525032025Copyright ©; 2025, Kondratieva T.K., Kondratieva E.V., Apt A.S.Copyright ©; 2025, Кондратьева Т.К., Кондратьева Е.В., Апт А.С.2025Kondratieva T.K., Kondratieva E.V., Apt A.S.Кондратьева Т.К., Кондратьева Е.В., Апт А.С.https://creativecommons.org/licenses/by/4.0https://iimmun.ru/iimm/article/view/17880

Tuberculosis (TB), primarily pulmonary TB, continues to pose a serious threat to public health, despite intensive studies investigating related pathogenesis, as well as development and testing of novel anti-TB drugs and vaccines. One of the reasons for such a slow progress in establishing effective TB spreading control as well as improving TB prophylaxis and treatment is recognized to be due to substantial shortage of our understanding mechanisms on immune response to and genetic control of the infection, as well as key defects interfering with ability of the host to combat progressive disease. Primarily, it is accounted for by the gaps in our knowledge on early phases of infection, because clinicians virtually never experience them in real-world practice, whilst the majority of existing animal models fail to adequately mimic the events occurring in human TB-infected lung. In this review, we briefly outline some unresolved issues related to TB immunity and genetics, specifically focusing at the first month of infection. Herein, we describe interactions between mycobacteria and diverse phagocyte types in the lung tissue as well as the consequences of mycobacterial phagocytosis by alveolar and interstitial macrophages, neutrophils, eosinophils and dendritic cells. Next, the issues concerning tuberculous granuloma classification and relevant functional diversity as well as difference in immunologist and pathologist viewpoint on nature of primary tuberculous lesion are discussed. Finally, the sequence of innate and adaptive immune reactions against mycobacteria, as well as T-cell — neutrophil interplay during TB course gains special attention. Based on personal studies assessing immune response dynamics and expression of immune activation/exhaustion markers on CD4+ T-cells in MHC II allele-specific TB-infected mice we discuss key phenotypes between genetically susceptible and relatively resistant animals.

Туберкулез (ТБ), прежде всего легочный, продолжает оставаться серьезной проблемой для здравоохранения, несмотря на интенсивные исследования патогенеза болезни, разработку и проверку новых лекарств и попытки создать новые вакцины против ТБ. Одной из причин столь медленного прогресса в решении задачи эффективного контроля за распространением этой инфекции и повышения эффективности ее профилактики и лечения признается недостаток фундаментальных знаний о механизмах иммунного ответа на инфекцию, генетического контроля этого ответа и ключевых дефектах, не позволяющих зараженному хозяину справится с прогрессированием болезни. В первую очередь, недостаток наших знаний касается ранних фаз инфекции, поскольку в обычной клинической практике врачи практически с ними не встречаются, а многие существующие экспериментальные модели ТБ на животных не вполне адекватно отражают события, происходящие в зараженных M. tuberculosis легких у человека. В этом обзоре мы кратко рассматриваем некоторые нерешенные проблемы иммунологии и генетики туберкулезной инфекции со специфическим акцентом на первый месяц развития инфекции. Описывается взаимодействие микобактерий с разными типами фагоцитов в легочной ткани и последствия захвата микобактерий альвеолярными и интерстициальными макрофагами, нейтрофилами, эозинофилами и дендритными клетками. Обсуждаются вопросы классификации туберкулезных гранулем, их функциональное разнообразие различия во взглядах на природу первичных очагов туберкулезной инфекции иммунологов и патологов. В заключительном разделе обзора особое внимание уделено последовательности включения в иммунный ответ против микобактерий реакций врожденного и адаптивного иммунитета, а также регуляции взаимодействия между нейтрофилами и Т-лимфоцитами при туберкулезе. На основании собственных данных о динамике развития иммунного ответа и экспрессии на Т-клетках CD4+ маркеров активации и ингибирования ответа при экспериментальном туберкулезе у мышей, отличающихся по аллелям MHC II, обсуждаются ключевые различия между генетически чувствительными и резистентными к инфекции животными.

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