ВНУТРИКЛЕТОЧНЫЕ СИСТЕМЫ ОБНАРУЖЕНИЯ ЭКЗОГЕННЫХ НУКЛЕИНОВЫХ КИСЛОТ И МЕХАНИЗМЫ ЗАПУСКА ИММУННЫХ РЕАКЦИЙ В ОТВЕТ НА ИНТЕРНАЛИЗАЦИЮ ЭКЗОГЕННОЙ ДНК

Резюме. В защитной системе клетки существуют специфические механизмы, детектирующие проникновение чужеродных молекул, так называемых патоген-ассоциированных молекулярных паттернов (ПАМП), в ее внутреннее пространство. Распознавание ПАМП происходит или с участием Tolllike рецепторов, или сопряжено с активностью цитозольных сенсоров. В последнее время большое внимание уделяется изучению процесса детекции нуклеиновых кислот, доставленных в цитозоль эукариотической клетки. К настоящему времени идентифицированы такие внутриклеточные сенсоры двуцепочечной ДНК, как STING, DAI, семейство NOD-like белков, RLH-геликазы, белки семейства HIN-200. Одни из этих факторов непосредственно взаимодействуют с двуцепочечной ДНК, другие являются охарактеризованными посредниками в передаче сигнала с неизвестного ДНК-сенсора. Результатом активации каскада событий, запускаемых цитозольной двуцепочечной ДНК, является индукция ядерных транскрипционных факторов NF-κB и IRF3/IRF7 и усиление продукции интерферона-бета, а также процессинг предшественников провоспалительных цитокинов IL-1β и IL-18 путем формирования инфламмасом. В настоящем обзоре обобщена информация, характеризующая пути реализации сигнала от момента определения внутриклеточной двуцепочечной ДНК до формирования клеточного иммунного ответа.

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