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

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.

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