mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-SPP-2450mimmun-2450Research ArticleОБЗОРЫREVIEWSStreptococcus pyogenes: феномен неиммунного связывания иммуноглобулинов человека и его роль в патологииStreptococcus pyogenes: phenomenon of nonimmune binding of human immunoglobulins and its role in pathologyhttps://orcid.org/0000-0001-7687-2348БуроваЛ. А.BurovaL. A.

Бурова Лариса Александровна – доктор медицинских наук, ведущий научный сотрудник отдела молекулярной микробиологии

197376, Санкт-Петербург, ул. Акад. Павлова, 12

Burova Larisa A., PhD, MD (Medicine), Leading Research Associate, Department of Molecular Microbiology

197376, St. Petersburg, Akad. Pavlov str., 12

lburova@yandex.ruСуворовА. Н.SuvorovA. N.

Суворов Александр Николаевич – доктор медицинских наук, член-корреспондент РАН, руководитель отдела молекулярной микробиологии

Санкт-Петербург

PhD, MD (Medicine), Corresponding Member, Russian Academy of Sciences, Head, Department of Molecular Microbiology

St. Petersburg

alexander_suvorov1@hotmail.comТотолянА. А.TotolianA. A.

Тотолян Артем Акопович – доктор медицинских наук, академик РАН, главный научный сотрудник Отдела молекулярной микробиологии

Санкт-Петербург

Totolian Artem A., PhD, MD (Medicine), Full Member, Russian Academy of Sciences, Main Research Associate, Department of Molecular Microbiology

St. Petersburg

Totolyan@hotmail.comФГБУ "Институт экспериментальной медицины"РоссияInstitute of Experimental MedicineRussian FederationФГБНУ «Институт экспериментальной медицины»РоссияInstitute of Experimental MedicineRussian Federation202220042022242217234Copyright © Бурова Л.А., Суворов А.Н., Тотолян А.А., 20222022Бурова Л.А., Суворов А.Н., Тотолян А.А.Burova L.A., Suvorov A.N., Totolian A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/2450

М- и М-подобные белки являются основными факторами патогенности широко распространенного и потенциально смертельного бактериального патогена Streptococcus pyogenes. Эти белки обеспечивают устойчивость микроба к врожденным и адаптивным иммунным реакциям, привлекая специфические белки человека на поверхность стрептококка. Неиммунное связывание иммуноглобулинов G (IgG) и A (IgA) через их Fc-домены М- и М-подобными белками было описано более 40 лет назад, но его значение в патогенности Streptococcus pyogenes нельзя считать окончательно решенным. Обнаружение данного феномена следует отнести к весьма значительным достижениям современной микробиологии, поскольку он оказал огромное влияние на создание инновационных подходов, технологий и средств микробиологической, иммунологической и молекулярной диагностики. Он также повлиял на фундаментальные исследования в области патогенеза актуальных инфекционных заболеваний и их осложнений, вызываемых S. pyogenes. Предполагалось, что неиммунное связывание иммуноглобулинов хозяина имеет значение в основном при иммунных состояниях на поверхности слизистых оболочек и в секрете, но не в плазме, в то время как другие исследования свидетельствовали о важности данного феномена в защите микробов от фагоцитоза в неиммунной крови макроорганизма. Было также показано, что эффект Fc-связывания повышает патогенность стрептококков как в первичном очаге инфекции, так и при хронизации процесса, способствуя развитию аутоиммунных заболеваний, вызванных инфекцией S. pyogenes, приводя к повреждению тканей у экспериментальных животных. Экспериментальный аутоиммунный процесс можно предупредить, используя введение животным очищенных Fc-фрагментов иммуноглобулинов, блокируя процесс на ранних стадиях его развития. Существенное место в патогенезе IgA – нефропатии (IgAN) принадлежит стрептококковым заболеваниям. IgAN описывают как мезангиально-пролиферативный процесс, обусловленный первоначальным отложениями IgA-Fcα белка в клетках почечного мезангиума. Литературные данные указывают на успешное моделирование отдельных признаков IgAN и расширяют наши представления о патогенных свойствах и функциях Fcα-рецепторных М-белков S. pyogenes. Рассмотренные в обзоре данные подчеркивают также актуальность выдвигаемых представлений о важной роли неиммунного связывания иммуноглобулинов в стрептококковой патологии, даже в случаях, различающихся по механизму развития. Эти исследования в том числе и возможный поиск средств и методов профилактической и потенциально терапевтической направленности требуют нового внимания к исследованиям связывания Fc-фрагментов иммуноглобулинов G (IgG) и A (IgA) М- и М-подобными белками Streptococcus pyogenes.

 

M and M-like proteins represent the main pathogenicity factors of Streptococcus pyogenes, a widely spread and potentially lethal bacterial pathogen. These proteins provide resistance of the microbe to innate and adaptive immune response, due to attraction of specific human proteins to the streptococcal surface. Nonimmune binding of immunoglobulins G (IgG) and A (IgA) via their Fc domains to M and M-like proteins was described over 40 years ago, but its role for the pathogenicity of Streptococcus pyogenes is far from definite resolution. The discovery of this phenomenon should be considered among quite significant achievements of modern microbiology, since it had a huge impact upon development of innovative approaches, technologies and tools for microbiological, immunological and molecular diagnostics. It also promoted fundamental studies in pathogenesis of distinct infectious states and their complications caused by S. pyogenes. The non-immune binding of host immunoglobulins was previously suggested to be important mainly in immune conditions on the surface of mucous membranes and their secretions, but not in blood plasma, whereas other studies have pointed to significance of this phenomenon in protecting microbes from phagocytosis in non-immune blood of the host. It was also shown that the effect of Fc-binding causes increased pathogenicity of streptococci both in primary focus of infection, and during chronical course of the process, thus contributing to development of autoimmune diseases caused by S. pyogenes infection and leading to tissue damage in experimental animals. The experimental autoimmune process can be prevented by administering purified Fc fragments of immunoglobulins to the animals, blocking this process at the early stages of its development. A significant place in pathogenesis of IgA nephropathy (IgAN) belongs to streptococcal diseases. IgAN has been described as a mesangial proliferative process, due to initial IgA-Fcα deposition in renal mesangium cells. The data from literature describe successful modeling of individual IgAN traits, and expand our understanding of pathogenic properties and functions of Fcα binding receptor M proteins of S. pyogenes. The data reviewed in the article also presume the relevance of recently proposed ideas about an important role of non-immune Ig binding in streptococcal diseases, even in cases that differ in their development mechanism. These studies, including possible search for tools and techniques of preventive and potentially therapeutic applications, require additional efforts to study the binding of Fc fragments of IgG and IgA to M and M-like proteins of Streptococcus pyogenes.

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