Взаимодействие бактериальных внеклеточных микровезикул и эукариотических клеток

Бактериальные внеклеточные микровезикулы (БМВ) секретируются патогенными, непатогенными и условно-патогенными бактериями. БМВ представляют собой сферические органеллы с бислойной мембраной, содержащие различные грузы: липополисахариды, патоген-ассоциированные молекулярные паттерны (PAMP), ДНК, РНК, сигнальные молекулы, белки, факторы устойчивости к антибиотикам, факторы вирулентности и токсины, обеспечивающие различные варианты иммунного ответа и благоприятствующие выживанию и распространению патогена в организме. Функции, связанные с выделением везикул, играют важную роль в способности микроорганизмов вызывать различные заболевания. БМВ помогают бактериям уклоняться от иммунной реакции хозяина, обеспечивают коммуникацию, выживание в стрессовой среде внутри хозяина во время инфекции, участвуют в формировании биопленок, а также помогают получить питание в среде с недостатком питательных веществ. Гетерогенность механизмов биогенеза обуславливают различия переносимых БМВ и их характеристик, включая степень вирулентности. Проникновение БМВ в клетки хозяина может осуществляться с помощью нескольких механизмов и способствует активации врожденных и адаптивных иммунных реакций. Обзор сфокусирован на исследованиях взаимодействия БМВ и различных типов эукариотических клеток, включая нейтрофилы, дендритные клетки, макрофаги, эпителиальные, эндотелиальные клетки. В зависимости от вида бактерий, типа клетки-мишени и количества везикул такое взаимодействие может привести к различным ответам: неиммуногенным, провоспалительным, цитотоксическим. Представлены субклеточные и молекулярные механизмы, связанные с участием внеклеточных микровезикул, в модулировании иммунного ответа хозяина. Стимуляция иммунного ответа обеспечивается усилением секреции провоспалительных цитокинов и хемокинов. В ряде случаев БМВ используют механизмы для ускользания от иммунного надзора: синтез противовоспалительных цитокинов, нарушение и ограничение фагоцитоза и хемотаксиса макрофагов, усиление протеолитического расщепления CD14 на поверхности макрофагов, нарушение антиген-презентирующей функции дендритных клеток и подавление индукции пролиферации Т-клеток, уменьшение интенсивности синтеза провоспалительных цитокинов, избегание прямого взаимодействия с клетками иммунной системы хозяина, разрушение нейтрофильных ловушек. Это позволяет выживать клеткам бактерий в организме человека и увеличить инвазивный потенциал, а также снижать избыточность воспалительных реакций, которые могут привести как к гибели самого патогена, так и к жизнеугрожающим повреждениям тканей и органов организма-хозяина. Дальнейшие исследования этих механизмов позволят получить новые и улучшить уже имеющиеся терапевтические подходы в лечении инфекционных заболеваний.

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