Russian Journal of Infection and ImmunityRussian Journal of Infection and ImmunityИнфекция и иммунитет2220-76192313-7398SPb RAACI63510.15789/2220-7619-2019-2-253-261REVIEWSОБЗОРЫUnknownMechanisms of interacting Helicobacter pylori with gastric mucosal epithelium. II. A reaction of gastric epithelium on Helicobacter pylori colonization and persistenceМеханизмы взаимодействия Helicobacter pylori c эпителием слизистой оболочки желудка. II. Реакция эпителия слизистой оболочки желудка в ответ на колонизацию и персистирование H. pyloriPozdeevO. K.ПоздеевО. К.
Russian Federation

PhD, MD (Medicine), Professor, Head of the Department of Microbiology

Contacts: Oskar K. Pozdeev, 420012, Russian Federation, Kazan, Butlerova str., 36, Kazan State Medical Academy

Поздеев Оскар Кимович, доктор мендицинских наук, профессор, зав. кафедрой микробиологии 

Адрес для переписки: Поздеев Оскар Кимович 420012, Россия, г. Казань, ул. Бутлерова, 36,

pozdeevoskar@rambler.ruPozdeevaA. O.ПоздееваА О
Russian Federation

Assistant of the Department of Therapy and Family Medicine

Поздеева Адель Оскаровна, ассистент кафедры терапии и семейной медицины

pozdeevoskar@rambler.ruValeevaYu. V.ВалееваЮ. В.
Russian Federation

PhD (Medicine), Associate Professor, Department of Emergency Medical Care and Simulatory Medicine

Валеева Юлия Владимировна, кандидат медицинских наук, доцент кафедры неотложной медицинской помощи и симуляционной медицины

val_iulia@mail.ruGulyaevP. E.ГуляевП. Е.
Russian Federation

Assistant of the Department of Microbiology

Гуляев Павел Евгеньевич, ассистент кафедры микробиологии �гии

just-esteto@mail.ruSavinovaA. N.СавиноваА. Н.
Russian Federation

PhD (Biology), Associate Professor, Department of Microbiology

Савинова Альфия Николаевна, кандидат биологических наук, доцент кафедры микробиологии

kazan-55@mail.ruKazan State Medical Academy — Branch Campus of the Russian Medical Academy of Continuous Professional EducationКазанская государственная медицинская академия — филиал ФГБОУ ДПО Российская медицинская академия непрерывного профессионального образования МЗ РФKazan (Volga region) Federal UniversityФГАОУ ВО Казанский (Приволжский) федеральный университетKazan State Medical UniversityФГБОУ ВО Казанский государственный медицинский университет МЗ РТ12072019922532610304201805042019Copyright ©; 2019, Pozdeev O.K., Pozdeeva A.O., Valeeva Y.V., Gulyaev P.E., Savinova A.N.Copyright ©; 2019, Поздеев О.К., Поздеева А.О., Валеева Ю.В., Гуляев П.Е., Савинова А.Н.2019Pozdeev O.K., Pozdeeva A.O., Valeeva Y.V., Gulyaev P.E., Savinova A.N.Поздеев О.К., Поздеева А.О., Валеева Ю.В., Гуляев П.Е., Савинова А.Н.https://creativecommons.org/licenses/by/4.0https://iimmun.ru/iimm/article/view/635

Gastric and duodenal recurrent inflammatory diseases have a high prevalence, but the role played by microbes in its development remained unclear. However, the data published in 1983 by Marshall and Warren about isolating Helicobacter pylori from the stomach mucosa of the patient with gastritis and proposing relevant cultivation methods was the turning point in investigating etiology of the upper digestive tract inflammatory disorders. Moreover, it was shown that the majority of H. pylori spp. are found within the gastric lumen upon colonization, whereas around 20% of them are attached to the epithelial cells in the stomach. In addition, effects of interacting H. pylori with gastric epithelium and activation of some defense mechanisms due to bacterial colonization and spreading were analyzed. It was found that along with triggering pro-inflammatory response induced by proteins VacA as well as phosphorylated/unphosphorylated CagA, wherein the latter is able to induce a set of protective reactions H. pylori disrupts intercellular contacts, affects epithelial cell polarity and proliferation, and activates SHP-2 phosphatase resulting in emerging diverse types of cellular responses. The activation mechanisms for the mitogen-activated protein kinase (MAPK) pathway were discussed. The ability of H. pylori to regulate apoptosis, particularly via its suppression, by expressing ERK kinase and protein MCL1 facilitating bacterial survival in the gastric mucosa as well as beneficial effects related to bacterial circulation on gastric epithelial cell survival elicited by anti-apoptotic factors were also examined. Of note, persistence of H. pylori are mainly determined by activating transcriptional factors including NF-κB, NFAT, SRF, T-cell lymphoid enhancing factor (TCF/LEF), regulating activity of MCL1 protein, in turn, being one of the main anti-apoptotic factors, as well as induced production of the migration inhibitory factor (MIF). The role of VacA cytotoxin in triggering epithelial cell apoptosis via caspase-mediated pathways was also considered. Infection with H. pylori is accompanied by release of proinflammatory cytokine cocktail detected both in vitro and in vivo. In particular, bacterial urease activating transcriptional factor NF-κB was shown to play a crucial role in inducing cytokine production. Moreover, such signaling pathways may be activated after H. pylori is attached to the cognate receptor in the gastric epithelial surface by interacting with CD74 and MHC class II molecules. Finally, a role for various CD4+ T cell subsets, particularly type 17 T helper cells (Th17) in inducing immune response against H. pylori antigens in gastric mucosa was revealed were also discussed.

Распространенность рецидивирующих воспалительных заболеваний желудка и двенадцатиперстной кишки велика, однако роль микробов в развитии данной патологии оставалась неясной. Переломный момент в изучении этиологии воспалительных заболеваний верхних отделов пищеварительного тракта произошел после опубликования B.J. Marshall и J.R. Warren (1983) результатов выделения Helicobacter pylori со слизистой оболочки желудка больного, страдающего гастритом, и методах культивирования этих бактерий. Большинство бактерий вида H. pylori при колонизации организма находятся в свободном состоянии, но около 20% присоединяется к эпителиальным клеткам желудка. Были проанализированы последствия взаимодействия H. pylori с эпителием слизистой оболочки желудка и активации защитных механизмов, вызванных колонизацией и циркуляцией бактерий. Показано, что наряду с запуском провоспалительного ответа, индуцированного белками VacA и CagA, в котором последний способен вызывать комплекс ответных реакций, как в фосфорилированной, так и в нефосфорилированной форме, H. pylori повреждает межклеточные контакты, нарушает полярность и пролиферацию эпителия, активирует фосфатазы SHP-2, что приводит к развитию различных клеточных ответов. Рассмотрены механизмы запуска митоген-активируемого протеинкиназного каскада (MAPK). Обсуждены способность H. pylori регулировать процесс апоптоза, а именно его подавления, через экспрессию киназы ERK и белка MCL1, что облегчает его выживание на слизистой желудка, а также позитивное влияние циркуляции бактерий на выживание эпителиоцитов посредством индукции антиапоптотических факторов в клетках эпителия желудка. В значительной мере такие процессы, как активация транскрипционных факторов (NF-κB, NFAT, SRF, T-клеточный лимфоидный энхансерный фактор [TCF/LEF]), регуляция активности белка MCL1, который в свою очередь является одним из основных антиапоптотических факторов, и индукция синтеза фактора торможения миграции (MIF) обусловливают персистенцию H. pylori. Рассмотрено участие цитотоксина VacA в индукции апоптоза эпителиоцитов посредством запуска каскадных реакций, осуществляемых каспазами. Инфицирование H. pylori сопровождается секрецией комплекса провоспалительных цитокинов, причем данные подтверждаются как in vitro, так и in vivo. Основную роль в выработке данных цитокинов играет уреаза, которая активирует транскрипционный фактор NF-κB. Кроме того, сигнальные системы эпителия желудка могут быть активированы в результате связывания бактерий с рецептором на поверхности эпителиоцитов (взаимодействие с CD74 и молекулами II класса главного комплекса гистосовместимости). Рассмотрено участие различных субпопуляций CD4+ T-клеток, в частности Т-хелперов 17 (Th17), в формировании иммунного ответа к антигенам H. pylori в слизистой оболочке желудка.

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