Russian Journal of Infection and ImmunityRussian Journal of Infection and ImmunityИнфекция и иммунитет2220-76192313-7398SPb RAACI116910.15789/2220-7619-ROI-1169REVIEWSОБЗОРЫInnate immune receptors in development of Mycobacterium tuberculosis infectionРоль рецепторов врожденного иммунитета в развитии инфекционного процесса, обусловленного Mycobacterium tuberculosisLapshtaevaA. V.ЛапштаеваА. В.
Russian Federation

Associate Professor, Department of Immunology, Microbiology and Virology.

430005, Saransk, Bol’shevistskaya str., 68, Phone: +7 (927) 177-35-55

Лапштаева Анна Васильевна - доцент кафедры иммунологии, микробиологии и вирусологии.

430005, Саранск, ул. Большевистская, 68, Тел.: 8 (927) 177-35-55

av_lapshtaeva@mail.ruZhivechkovaE. A.ЖивечковаЕ. А.
Russian Federation

Resident of the Department of Hospital Therapy No. 2, Faculty of Medicine.

Moscow

Ординатор кафедры госпитальной терапии № 2 лечебного факультета.

Москва

e.zhivechkova@yandex.ruSychevI. V.СычевИ. В.
Russian Federation

PhD Student.

Saransk

Аспирант Медицинского института.

Саранскgodsgiftof@gmail.comEvsegneevaI. V.ЕвсегнееваИ. В.
Russian Federation

PhD, MD (Medicine), Professor, Professor of the Department of Clinical Immunology and Allergology.

Moscow

Доктор медицинских наук, профессор, профессор кафедры клинической иммунологии и аллергологии.

Москва

evsegneeva@mail.ruNovikovV. V.НовиковВ. В.

PhD, MD (Medicine), Professor, Head of the Department of Molecular Biology and Immunology, N.I. Lobachevskii NRNNSU; Head of the Department of Immunochemisrty, I.N. Blokhina Nizhny Novgorod RIEM.

Nizhny Novgorod

Доктор медицинских наук, профессор, заведующий кафедрой молекулярной биологии и иммунологии НИНГУ им. Н.И. Лобачевского; зав. лабораторией иммунохимии НГИИЭМ им. академика И.Н. Блохиной.

Нижний Новгород

mbre@mail.ruNational Research Ogarev Mordovia State University, Medical InstituteФГБОУВО Мордовский государственный университет им. Н.П. Огарева, медицинский институтPirogov Russian National Research Medical University (RNRMU)ФГАОУВО Российский национальный исследовательский медицинский университет им. Н.И. Пирогова Минздрава РоссииI.M. Sechenov First Moscow State Medical UniversityФГАОУ ВО Первый Московский государственный медицинский университет им. И.М. Сеченова Минздрава РоссииN.I. Lobachevskii National Research Nizhny Novgorod State UniversityФГАОУ ВО Национальный исследовательский Нижегородский государственный университет им. Н.И. ЛобачевскогоI.N. Blokhina Nizhny Novgorod Research Institute of Epidemiology and MicrobiologyФБУН Нижегородский НИИ эпидемиологии и микробиологии им. академика И.Н. Блохиной0704202010135482203201910092019Copyright ©; 2020, Lapshtaeva A.V., Zhivechkova E.A., Sychev I.V., Evsegneeva I.V., Novikov V.V.Copyright ©; 2020, Лапштаева А.В., Живечкова Е.А., Сычев И.В., Евсегнеева И.В., Новиков В.В.2020Lapshtaeva A.V., Zhivechkova E.A., Sychev I.V., Evsegneeva I.V., Novikov V.V.Лапштаева А.В., Живечкова Е.А., Сычев И.В., Евсегнеева И.В., Новиков В.В.https://creativecommons.org/licenses/by/4.0https://iimmun.ru/iimm/article/view/1169

According to the World Health Organization, over 10 million new tuberculosis cases are reported annually worldwide. According to the 2017 Federal State Statistics Service Report, incidence rate for active TB infection in the Russian Federation was 109.8 cases per 100,000 population, of which 41.3% accounted for chronic disease form. Regardless of climatic conditions, high prevalence of TB infection, is not only due to high Mycobacterium tuberculosis viability, but also its ability for long persistence in human body and reactivation after an unlimited period of dormancy. The outcome of infection is largely determined by host immunoreactivity and its ability to develop protective immune response. In addition, status of immune system also underlies tuberculosis course after the onset: either as a localized form, or as a form with extensive damage to the lungs and even other organs observed in generalized infection. In recent decades, a great attention was paid to examining mechanisms of adaptive cell immunity played in pathogenesis of TB infection. No doubt, adaptive immunity is a powerful defense system providing a targeted specific immune response, but now it is becoming clear that it represents solely an effector arm of innate immunity. Innate immunity is a phylogenetically more ancient, inherited system largely aimed at ensuring rapid pathogen elimination and preventing development of infection at early stages when adaptive immunity ongoing antigen-specific maturation. Mechanisms of innate immunity mediated by cells, diverse receptors, molecules and their complexes, found on various cells. Activation of innate immunity begins with recognition of conserved molecular groups present in various pathogens called pathogen-associated molecular patterns (PAMPs), which are sensed by pathogen recognition receptors (PRRs). Here, we review current data on the role of innate receptors in recognizing M. tuberculosis-derived PAMPs, production of immunoregulatory cytokines and activation of signaling pathways playing a crucial role in the regulation of necroptosis, apoptosis and autophagy of infected macrophages. Significance of innate mucosal factors in implementing immune response to M. tuberculosis is discussed. In particular, Toll-like receptors, scavenger-receptors, mannose receptor, DC-SIGN etc. were described to participate in development of M. tuberculosis immunity. The data on single nucleotide polymorphic variants for innate genes are shown, which predispose to developing tuberculosis and affecting its course.

Согласно данным Всемирной организации здравоохранения, ежегодно во всем мире регистрируется свыше 10 млн новых случаев туберкулеза. В Российской Федерации, по данным Федеральной службы государственной статистики, в 2017 г. на 100 тыс. населения зарегистрировано 109,8 случаев активного туберкулеза, из которых 41,3% имели запущенную форму заболевания. Повсеместная распространенность заболевания независимо от климатических условий обусловлена не только высокой выживаемостью Mycobacterium tuberculosis, но и способностью возбудителя длительно персистировать в организме человека и реактивироваться через неограниченный период времени. Итог инфицирования в значительной степени определяется иммунореактивностью самого организма-хозяина и его готовностью к развитию протективного иммунного ответа. Кроме того, уже после развития болезни состояние иммунной системы определяет и течение туберкулеза: либо в виде ограниченной формы, либо с обширным поражением легких и даже других органов, что наблюдается при генерализованной инфекции. В последние десятилетия большое внимание исследователей было направлено на изучение механизмов клеточного адаптивного иммунитета в патогенезе туберкулезной инфекции. Безусловно, адаптивный иммунитет является мощной защитой, обеспечивающей целенаправленный специфический иммунный ответ, однако в настоящее время становится понятным, что он является лишь эффекторным звеном врожденного иммунитета. Врожденный иммунитет — филогенетически более древняя, наследственно закрепленная система, основной задачей которой является обеспечение быстрой элиминации патогена и предотвращение развития инфекции на ранних стадиях, когда механизмы адаптивного иммунитета отсутствуют. Механизмы врожденного иммунитета представлены клетками, разнообразными рецепторами, молекулами и их комплексами, присутствующими на разных клетках и имеющими одинаковое предназначение. Активация врожденного иммунитета начинается с распознавания одинаковых групп молекул, присутствующих у различных патогенов, — патоген-ассоциированных молекулярных паттернов (pathogen-accociated molecular patterns — PAMPs), осуществляемого с помощью паттерн-распознающих рецепторов (pathogen recognition receptops — PRRs). В обзоре приводятся данные о роли рецепторов врожденного иммунитета в распознавании PAMPs, присущих Mycobacterium tuberculosis, в продукции иммунорегуляторных цитокинов и в активации сигнальных путей, играющих критическую роль в регуляции некроптоза, апоптоза и аутофагии инфицированных макрофагов. Рассматривается значение факторов врожденного мукозального иммунитета в реализации иммунного ответа на M. tuberculosis. Описано участие Toll-подобных и скавенджер-рецепторов, манноз-ного рецептора, DC-SIGN и других в развитии иммунитета против M. tuberculosis. Представлены данные о полиморфных вариантах генов врожденного иммунитета, формирующих предрасположенность к туберкулезу и оказывающих влияние на характер его течения.

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