mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-2013-5-413-430mimmun-658Research ArticleОБЗОРЫREVIEWSВНУТРИКЛЕТОЧНЫЕ СИСТЕМЫ ОБНАРУЖЕНИЯ ЭКЗОГЕННЫХ НУКЛЕИНОВЫХ КИСЛОТ И МЕХАНИЗМЫ ЗАПУСКА ИММУННЫХ РЕАКЦИЙ В ОТВЕТ НА ИНТЕРНАЛИЗАЦИЮ ЭКЗОГЕННОЙ ДНКINTRACELLULAR SYSTEMS FOR DETECTION OF EXOGENOUS NUCLEIC ACIDS AND TRIGGERING MECHANISMS OF IMMUNE RESPONSE TO DNA INTERNALIZATIONАлямкинаЕ. А.AlyamkinaE. A.

к.б.н., научный сотрудник лаборатории индуцированных клеточных процессов

PhD (Biology), Laboratory of Induced Cellular Processes

labmolbiol@mail.ruДолговаЕ. В.DolgovaE. V.

к.б.н., научный сотрудник лаборатории индуцированных клеточных процессов

PhD (Biology), Research Associate, Laboratory of Induced Cellular Processes

labmolbiol@mail.ruПроскуринаА. С.ProskurinaA. S.

к.б.н., научный сотрудник лаборатории индуцированных клеточных процессов

PhD (Biology), Laboratory of Induced Cellular Processes

labmolbiol@mail.ruРогачевВ. А.RogachevV. A.

к.б.н., научный сотрудник лаборатории индуцированных клеточных процессов

PhD (Biology), Research Associate, Laboratory of Induced Cellular Processes

labmolbiol@mail.ruОстанинА. А.OstaninA. A.

д.м.н., профессор, главный научный сотрудник лаборатории клеточной иммунотерапии

PhD, MD (Medicine), Professor, Chief Research Associate, Laboratory of Cellular Immunotherapy

labmolbiol@mail.ruЧерныхЕ. Р.ChernykhE. R.

д.м.н., профессор, заместитель директора по науке

PhD, MD (Medicine), Professor, Deputy Director for Research

labmolbiol@mail.ruБогачевС. С.BogachevS. S.

д.б.н., заведующий лабораторией индуцированных клеточных процессов

630090, Россия, г. Новосибирск, пр. акад. Лаврентьева, 10. Тел.: 8 (383) 363-49-18, доб. 1017

PhD, MD (Biology), Chief, Laboratory of Induced Cellular Processes

labmolbiol@mail.ruШурдовМ. А.ShurdovM. A.

к.б.н., директор

PhD (Biology), Director

labmolbiol@mail.ruФГБУН «Институт цитологии и генетики» СО РАН, г. НовосибирскРоссияInstitute of Cytology and Genetics, Russian Academy of Sciences, Siberian Branch, NovosibirsRussian FederationФГБУ «Научно-исследовательский институт клинической иммунологии» СО РАМН, г. НовосибирскРоссияResearch Institute of Clinical Immunology, Russian Academy of Medical Sciences, Siberian Branch, NovosibirskRussian FederationФГБУН «Институт цитологии и генетики» СО РАН, г. Новосибирск; ООО «Панаген», г. Горно-АлтайскРоссияInstitute of Cytology and Genetics, Russian Academy of Sciences, Siberian Branch, Novosibirs; LLC “PANAGEN”, Gorno-AltaiskRussian FederationООО «Панаген», г. Горно-АлтайскРоссияLLC “PANAGEN”, Gorno-AltaiskRussian Federation201325072014155413430Copyright © Алямкина Е.А., Долгова Е.В., Проскурина А.С., Рогачев В.А., Останин А.А., Черных Е.Р., Богачев С.С., Шурдов М.А., 20142014Алямкина Е.А., Долгова Е.В., Проскурина А.С., Рогачев В.А., Останин А.А., Черных Е.Р., Богачев С.С., Шурдов М.А.Alyamkina E.A., Dolgova E.V., Proskurina A.S., Rogachev V.A., Ostanin A.A., Chernykh E.R., Bogachev S.S., Shurdov M.A.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/658

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.

Abstract. There are some specific mechanisms in cell that detect the invasion into the cell of any foreign molecules, so-called pathogen-associated molecular patterns (PAMPs). The recognition of these PAMPs is realized by Toll-like receptors or is due to the cytosolic sensors action. In recent years much attention is directed to the investigation of foreign nucleic acids sensing and detection in cell. Nowadays some sensors of doublestranded DNA, such as STING, DAI, members of NOD-like protein family, RIG-like helicases, proteins of HIN-200 family are identified. Some of sensors interact with double-stranded DNA directly. The others are characterized as mediators of signal transduction from unknown DNA-sensor in the series of following molecular events. Induction of nuclear transcription factors NF-κB and IRF3/IRF7 to produce IFNβ or processing of proinflammatory cytokines IL-1β and IL-18 by means of inflammasome formation is a result of activation of cascade events induced by cytosolic DNA. In the review we combine information concerning signaling pathways characterized sensing of intracellular double-stranded DNA that results in the development of the cellular immune response.

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