mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-IOS-2075mimmun-2075Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESВлияние стрептококковой аргининдеиминазы на формирование лейкоцитарного инфильтрата в модели воздушного кармана у мышейInfluence of streptococcal arginine deiminase on the leukocyte infiltration in murine air pouch modelСтариковаЭ. А.StarikovaE. A.

Старикова Элеонора Александровна – кандидат биологических наук, старший научный сотрудник отдела иммунологии

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

Starikova Eleonora A., PhD (Biology), Senior Research Associate, Department of Immunology

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

 

Starickova@yandex.ruКудрявцевИ. В.KudryavtsevI. V.

Кудрявцев Игорь Владимирович – кандидат биологических наук, заведующий лабораторией иммунорегуляции, отдел иммунологии

Санкт-Петербург 

Kudryavtsev Igor V., PhD (Biology), Head, Laboratory of Immunoregulation, Department of Immunology

St. Petersburg

igorek1981@yandex.ruБуроваЛ. А.BurovaL. A.

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

Санкт-Петербург

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

St. Petersburg

lburova@yandex.ruЛебедеваА. М.LebedevaA. M.

Лебедева Александра Михайловна – кандидат биологических наук, научный сотрудник отдела иммунологии

Санкт-Петербург 

Lebedeva Aleksandra M., PhD (Biology), Research Associate, Department of Immunology

St. Petersburg

aml1987@mail.ruМамедоваДж. Т.MammedovaJ. T.

Маммедова Дженнет Тумаровна – научный сотрудник отдела иммунологии

Санкт-Петербург 

Mammedova Jennet T., Research Associate, Department of Immunology

St. Petersburg

jennet_m@mail.ruФрейдлинИ. С.FreidlinI. S.

Фрейдлин Ирина Соломоновна – доктор медицинских наук, член-корреспондент РАН, главный научный сотрудник отдела иммунологии

Санкт-Петербург

Freidlin Irina S., PhD, MD (Medicine), Corresponding Member, Russian Acdemy of Sciences, Main Research Associate, Department of Immunology

St. Petersburg

irinaf-n@yandex.ruФГБНУ "Институт экспериментальной медицины"Institute of Experimental Medicine20203112202022611211130Copyright © Старикова Э.А., Кудрявцев И.В., Бурова Л.А., Лебедева А.М., Мамедова Д.Т., Фрейдлин И.С., 20212021Старикова Э.А., Кудрявцев И.В., Бурова Л.А., Лебедева А.М., Мамедова Д.Т., Фрейдлин И.С.Starikova E.A., Kudryavtsev I.V., Burova L.A., Lebedeva A.M., Mammedova J.T., Freidlin I.S.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/2075

Многие патогенные микроорганизмы экспрессируют аргининдеиминазу – фермент, который катализирует гидролиз L-аргинина в цепи биохимических реакций, направленных на синтез АТФ в бактериальных клетках. L-аргинин является условно заменимой, протеиногенной аминокислотой и играет важную роль в регуляции функций клеток иммунной системы в организме млекопитающих. Истощение L-аргинина может приводить к ослаблению иммунной защиты. Многие патогенные микроорганизмы используют стратегию истощения L-аргинина в микроокружении клеток организма хозяина для улучшения условий диссеминации. Бактериальная аргининдеиминаза может являться фактором патогенности, действие которого направлено на дисрегуляцию процессов воспаления и иммунного ответа. В целом влияние аргининдеиминазы на клетки иммунной системы может быть обусловлено нарушением продукции регуляторных провоспалительных молекул, таких как NO, и, связанными с этим, нарушениями активации, миграции и дифференцировки отдельных популяций лейкоцитов. Цель данного исследования состояла в изучении влияния аргининдеиминазы на формирование воспалительного клеточного инфильтрата при стрептококковой инфекции в модели воздушного кармана у мышей. Исследование проводили с использованием S. pyogenes M49-16, экспрессирующего аргининдеиминазу и его изогенного мутанта S. pyogenes M49-16delArcA с инактивированным геном аргининдеиминазы. В работе с помощью методов проточной цитометрии на разных сроках инфекции проводили анализ субпопуляционного состава воспалительного инфильтрата у мышей, зараженных исходным штаммом S. pyogenes M49-16 и его изогенным мутантом S. pyogenes M49-16delArcA. Было показано, что воспалительная реакция достигала пика развития через 6 часов и была выражена сильнее у мышей, инфицированных мутантным штаммом, о чем свидетельствовало одновременное и более выраженное повышение абсолютного количества лейкоцитов всех популяций в очаге воспаления у этой группы мышей по сравнению с мышами, инфицированными исходным штаммом. Несмотря на снижение абсолютного количества лейкоцитов в составе воспалительного инфильтрата в обеих группах мышей на сроке 24 часа, в группе мышей, зараженных мутантным штаммом, эта тенденция была выражена сильнее. Сравнение формирования воспалительного инфильтрата у мышей, зараженных исходным и мутантным штаммами, показало, что аргининдеиминаза может являться фактором патогенности, приводящим к дисрегуляции защитных реакций врожденного иммунитета за счет нарушения миграции лейкоцитов в очаг инфекции.

Numerous pathogens express arginine deiminase, an enzyme that catalyzes the hydrolysis of L-arginine in a chain of biochemical reactions aimed at the synthesis of ATP in bacterial cells. L-arginine is a semi-essential, proteinogenic amino acid that plays an important role in regulating the functions of the immune system cells in mammals. Depletion of L-arginine may cause a weakening of the immune reaction. In order to improve the conditions of dissemination, many pathogens use a strategy of L-arginine depletion in the microenvironment of host cells. Bacterial arginine deiminase can be a pathogenicity factor aimed for dysregulating the processes of inflammation and immune response. In general, the effect of arginine deiminase on immune cells may result into disturbed production of regulatory proinflammatory molecules, such as NO, and related substances, inhibition of activation, migration and differentiation of individual leukocyte subsets. The aim of this study was to investigate the effect of arginine deiminase on the formation of inflammatory infiltrate in murine air pouch model of streptococcal infection. Materials and methods: The study was performed using S. pyogenes M49-16 expressing arginine deiminase and its isogenic mutant S. pyogenes M49-16delArcA with inactivated arginine deiminase gene. The flow cytometry analysis of the inflammatory infiltrate leukocytes subpopulation in mice infected with the original strain of S. pyogenes M49-16 and its isogenic mutant S. pyogenes M49-16delArcA at different periods of infection was performed. It was shown that the inflammation reached its peak 6 hours after streptococcal inoculation, being more pronounced in mice infected with the mutant strain. Тhis finding was affirmed by a simultaneous and more pronounced increase in the absolute numbers of all leukocyte subsets in the focus of inflammation in this group of mice when compared to mice infected with original bacterial strain. Despite the decrease in the absolute number of all leukocyte types in the inflammatory infiltrate in both groups of mice for 24 hours, this trend was more pronounced in the group of mice infected with mutant microbial strain. Comparison of the inflammatory infiltrates developing in mice infected with original versus mutant strains showed that arginine deiminase may be a pathogenicity factor leading to dysregulation of protective immune response, due to impaired migration of white blood cells to the site of infection.

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