The aim of review

gastro-j

Российский журнал гастроэнтерологии, гепатологии, колопроктологии

Russian Journal of Gastroenterology, Hepatology, Coloproctology

1382-43762658-6673

«Gastro» LLC

gastro-j-1017

Research Article

НАЦИОНАЛЬНАЯ ШКОЛА ГАСТРОЭНТЕРОЛОГОВ, ГЕПАТОЛОГОВ

NATIONAL COLLEGE OF GASTROENTEROLOGISTS, HEPATOLOGISTS

Роль дефектов аутофагии и значение адгезивно-инвазивных Escherichia coli в генезе болезни Крона

Role of autophagy defects and significance of adherent-invasive Escherichia coli in Crohn's disease development

Маев

И. В.

Mayev

I. V.

Маев Игорь Вениаминович — доктор медицинских наук, профессор, заслуженный врач РФ, заслуженный деятель науки РФ, член-корреспондент РАН, проректор по учебной работе, заведующий кафедрой пропедевтики внутренних болезней и гастроэнтерологии

Mayev Igor V — MD, PhD, professor, honored doctor of the Russian Federation, honored scientist of the Russian Federation, corresponding member of the Russian Academy of Science, vice-rector for academic activity, head of the chair of internal diseases propedeutics and gastroenterology

Андреев

Д. Н.

Andreev

D. N.

Андреев Дмитрий Николаевич — ассистент кафедры пропедевтики внутренних болезней и гастроэнтерологии

Andreev Dmitry N – assistant-professor, Chair of internal diseases propedeutics and gastroenterology

dna-mit8@mail.ru

Ракитина

Д. В.

Rakitina

D. V.

Ракитина Дарья Викторовна — кандидат биологических наук, старший научный сотрудник лаборатории протеомного анализа

Rakitina Darya V. — Cand. Biol. Sci., senior research associate, Laboratory of proteomic analysis

Байкова

Ю. П.

Baykova

Yu. P.

Байкова Юлия Павловна — кандидат биологических наук, научный сотрудник лаборатории протеомного анализа

Baykova Yuliya P — Cand. Biol. Sci., research associate, Laboratory of proteomic analysis

ГБОУ ВПО «Московский государственный медико-стоматологический университет им. А.И. Евдокимова» Минздрава РоссииРоссияState educational government-financed institution of higher professional education «Yevdokimov Moscow State University of Medicine and Dentistry», Ministry of Healthcare of the Russian FederationRussian Federation

ФГБУН «Научно-исследовательский институт физико-химической медицины» Федерального медико-биологического агентстваРоссияState educational government-financed institution of continuing professional education «Scientific research institute of physical and chemical medicine», Federal Medical-Biological AgencyRussian Federation

2015

18072015

2536169

2015

Маев И.В., Андреев Д.Н., Ракитина Д.В., Байкова Ю.П.

Mayev I.V., Andreev D.N., Rakitina D.V., Baykova Y.P.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://www.gastro-j.ru/jour/article/view/1017

Цель обзора. Представить новые данные о роли молекулярно-генетических нарушений врожденного иммунитета при болезни Крона (БК), а также осветить значение адгезивно-инвазивных Escherichia coli (АИEC) как микроорганизмов, потенциально участвующих в генезе БК.Основные положения. С современных позиций этиология БК носит комплексный характер и определяется такими компонентами, как генетическая предрасположенность, инфекционный агент и средовые факторы. Одним из базовых для БК генетически-детерминированных нарушений врожденного иммунитета является альтерация процесса аутофагии (дефекты генов NOD2/CARD15, ATG16L1, IRGM). Помимо этого для БК характерны дисбиотические нарушения кишечника, ассоциированные с повышением количества микроорганизмов, обладающих патогенным потенциалом, в частности АИEC. Данный фенотип микроорганизмов обладает способностями к адгезии к эпителиоцитам слизистой оболочки, внедрению в них, а также к активной репликации внутри макрофагов. У лиц с генетической предрасположенностью репликация АИEC в макрофагах в условиях сниженного клиренса микроорганизмов за счет альтерации процесса аутофагии может индуцировать иррациональный иммунный ответ с развитием характерных для БК воспалительных изменений.Заключение. В основе современной модели развития БК лежат дисбиотические нарушения кишечника, ассоциированные с повышением количества микроорганизмов, обладающих патогенным потенциалом (АИEC), а также генетически-детерминированные дефекты механизмов врожденного иммунитета (альтерация аутофагии). Безусловно, такая модель скорее всего правомочна только для определенной части популяции пациентов с БК, тем не менее на настоящий момент она является базисом для дальнейшего изучения этиопатогенеза рассматриваемой патологии.

The aim of review

The aim of review. To present new data on a role of molecular genetic disorders of innate immunity at Crohn's disease (CD), and to demonstrate the role of adherent-invasive Escherichia coli (AIEC) as the microorganisms potentially involved in CD development.

Summary

Summary. According to modern concept, etiology of CD has complex nature and is determined by genetic predisposition, infectious agents and environmental factors. Alteration of autophagy process (defects of NOD2/ CARD15, ATG16L1, IRGM genes) is one of genetically determined disorders of innate immunity typical for CD. Besides that intestinal dysbiotic disorders associated with elevation of quantity of microorganisms, possessing pathogenic potential, in particular AIEC is characteristic for CD. This phenotype of microorganisms has capacity of adhesion to mucosal epithelial cells, invasion, and active replication inside macrophages. In patients with genetic predisposition AIEC replication in macrophages at reduced clearance of microorganisms due to alteration of autophagy process can induce the unsound immune response with development inflammatory changes characteristic for CD.

Conclusion

Conclusion. Intestinal dysbiosis associated with elevation of quantity of microorganisms, possessing pathogenic potential (AIEC), as well as genetically — determined defects of innate immunity (autophagy alteration) lay in a basis of up-to-date model of CD development. Undoubtedly, such model is most likely relevant only for selected part of CD patients, nevertheless for the present moment it is the basic for the further studying of CD etiopathogenesis.

болезнь Кронаврожденный иммунитетаутофагияксенофагиямикробиотаNOD2/CARD15ATG16L1IRGMEscherichia coliAIEC

Crohn's diseaseinnate immunityautophagyxenophagymicrobiotaNOD2/CARD15ATG16L1IRGMEscherichia coliAIEC

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The authors declare that there are no conflicts of interest present.