Journal of microbiology, epidemiology and immunobiologyJournal of microbiology, epidemiology and immunobiologyЖурнал микробиологии, эпидемиологии и иммунобиологии0372-93112686-7613Central Research Institute for Epidemiology127210.36233/0372-9311-323REVIEWSОБЗОРЫReview ArticleMechanisms of Toll-like receptor tolerance induced by microbial ligandsМеханизмы формирования толерантности Toll-подобных рецепторов под действием микробных лигандовhttps://orcid.org/0000-0002-2629-9616BulgakovaIrina D.БулгаковаИрина Дмитриевна
Russian Federation

junior researcher, Laboratory of molecular immunology, postgraduate and assistant of the Microbiology, virology and immunology department

м.н.с. лаб. молекулярной иммунологии, аспирант и ассистент каф. микробиологии, вирусологии и иммунологии

bulgakova_i_d@staff.sechenov.ruhttps://orcid.org/0000-0003-1757-8389SvitichOxana A.СвитичОксана Анатольевна
Russian Federation

D. Sci. (Med.), Corresponding member of RAS, Head, Professor of Microbiology, virology and immunology department

д.м.н., член-корр. РАН, зав. лаб. молекулярной иммунологии, директор, проф. каф. микробиологии, вирусологии и иммунологии

svitich_o_a@staff.sechenov.ruhttps://orcid.org/0000-0002-0017-1892ZverevVitaly V.ЗверевВиталий Васильевич
Russian Federation

D. Sci. (Med.), Academician of RAS, Scientific head, Professor, Head, Microbiology, virology and immunology department

д.б.н., акад. РАН, науч. рук., проф., зав. каф. микробиологии, вирусологии и иммунологии

zverev_v_v@staff.sechenov.ruI. Mechnikov Research Institute for Vaccines and SeraНаучно-исследовательский институт вакцин и сывороток им. И.И. МечниковаI.M. Sechenov First Moscow State Medical UniversityПервый Московский государственный медицинский университет им. И.М. Сеченова1512202299670872109082022Copyright ©; 2022, Bulgakova I.D., Svitich O.A., Zverev V.V.Copyright ©; 2022, Булгакова И.Д., Свитич О.А., Зверев В.В.2022Bulgakova I.D., Svitich O.A., Zverev V.V.Булгакова И.Д., Свитич О.А., Зверев В.В.https://creativecommons.org/licenses/by/4.0https://microbiol.crie.ru/jour/article/view/1272

Some microorganisms can develop tolerance. On the one hand, it allows pathogenic microbes to escape immune surveillance, on the other hand, it provides the possibility to microbiota representatives to colonize different biotopes and build a symbiotic relationship with the host. Complex regulatory interactions between innate and adaptive immune systems as well as stimulation by antigens help microbes control and maintain immunological tolerance. An important role in this process belongs to innate immune cells, which recognize microbial components through pattern-recognition receptors. Toll-like receptors (TLRs) represent the main class of these receptors. Despite the universality of the activated signaling pathways, different cellular responses are induced by interaction of TLRs with microbiota representatives and pathogenic microbes, and they vary during acute and chronic infection. The research on mechanisms underlying the development of TLR tolerance is significant, as the above receptors are involved in a wide range of infectious and noninfectious diseases; they also play an important role in development of allergic diseases, autoimmune diseases, and cancers. The knowledge of TLR tolerance mechanisms can be critically important for development of TLR ligand-based therapeutic agents for treatment and prevention of multiple diseases.

Некоторые микроорганизмы способны формировать толерантность. С одной стороны, это позволяет патогенным микробам ускользать от иммунного надзора, с другой стороны — даёт возможность представителям микробиоты колонизировать различные биотопы и выстраивать симбиотические отношения с макроорганизмом. Сложные регуляторные взаимодействия врождённого и адаптивного иммунитета, а также стимуляция антигенами позволяют микробам управлять состоянием иммунологической толерантности. Важную роль в этом процессе играют клетки врождённого иммунитета, которые распознают компоненты микробов при помощи паттерн-распознающих рецепторов. Основным классом этих рецепторов являются Toll-подобные рецепторы (TLRs). При этом, несмотря на универсальность активируемых сигнальных путей, можно наблюдать различные клеточные ответы при взаимодействии TLRs с представителями микробиоты и патогенными микробами, они также будут различаться при острой и хронической инфекции. Изучение механизмов формирования толерантности TLRs имеет большую ценность, поскольку эти рецепторы вовлечены в широкий спектр инфекционных и неинфекционных заболеваний, а также играют важную роль в развитии аллергических, аутоиммунных патологий и онкологических заболеваний. Понимание механизмов формирования толерантности TLRs может также внести существенный вклад в разработку препаратов на основе лигандов этих рецепторов для лечения и профилактики многих заболеваний.

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