mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-ROI-2519mimmun-2519Research ArticleОБЗОРЫREVIEWSРоль IFNγ в патогенезе инфекции, вызванной SARS-CoV-2Role of IFNγ in pathogenesis of SARS-CoV-2 infectionhttps://orcid.org/0000-0002-2767-6938АртамоновА. А.ArtamonovA. A.

студент

Санкт-Петербург

Student

St. Petersburg

Artamonov.Alandr@yandex.ruhttps://orcid.org/0000-0001-7892-2783НикитинЮ. В.NikitinYu. V.

Никитин Юрий Владимирович, врач – аллерголог-иммунолог центра клинической лабораторной диагностики, преподаватель кафедры клинической биохимии и лабораторной диагностики

194044, Санкт-Петербург, ул. Акад. Лебедева, 6, лит. ВТел.: 8 (981) 719-04-84

Nikitin Yury V. Clinical Allergologist-Immunologist, Center of Clinical Laboratory Diagnostics; Lecturer, Department of Clinical Biochemistry and Laboratory Diagnostics

194044, St. Petersburg, Acad. Lebedev str., 6, bldg ВPhone: 7 (981) 719-04-84

dr.iuriinikitin@gmail.comhttps://orcid.org/0000-0002-0694-8586МешковаМ. Е.MeshkovaM. E.

к.б.н., старший преподаватель кафедры клинической биохимии и лабораторной диагностики

Санкт-Петербург

PhD (Biology), Senior Lecturer, Department of Clinical Biochemistry and Laboratory Diagnostics

St. Petersburg

meshkova.63@mail.ruhttps://orcid.org/0000-0002-8899-7524ИвановА. М.IvanovA. M.

д.м.н., профессор, член-корр. РАН, заведующий кафедрой клинической биохимии и лабораторной диагностики

Санкт-Петербург

PhD, MD (Medicine), Professor, Corresponding Member, Russian Academy of Sciences, Head, Department of Clinical Biochemistry and Laboratory Diagnostics

St. Petersburg

iamvma@mail.ruФГБВОУ ВО «Военно-медицинская академия имени С.М. Кирова»РоссияS.M. Kirov Military Medical AcademyRussian Federation202231102022245903910Copyright © Артамонов А.А., Никитин Ю.В., Мешкова М.Е., Иванов А.М., 20222022Артамонов А.А., Никитин Ю.В., Мешкова М.Е., Иванов А.М.Artamonov A.A., Nikitin Y.V., Meshkova M.E., Ivanov A.M.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/2519

На сегодняшний день нет единого мнения, объясняющего взаимосвязь разнящихся концентраций IFNγ и тяжести течения инфекции вызванной SARS-CoV-2 у отдельных групп пациентов. Целью данной статьи является изучение и анализ исследований и публикаций, в совокупности формирующих потенциально объективный взгляд на роль IFNγ в патогенезе COVID-19.

В данной статье освещены актуальные данные об иммунологической роли IFNγ. Охарактеризована способность IFNγ оказывать влияние на дифференцировку наивных Т-хелперов выступая в роли поляризующего фактора, активировать главный комплекс гистосовместимости I и II класса за счет увеличения экспрессии субъединицы молекул MHC I/II, ингибировать репликацию вирусных частиц путем инициации экспрессии интерферон-стимулируемых генов с последующим синтезом белков, обладающих противовирусной активностью, а также активировать продукцию цитокинов Т-клетками, усиливая цитотоксическую активность Т-киллеров. IFNγ оказывает иммуностимулирующее и иммуномодулирующее действие через гены STAT1, SOCS1, PIAS, регулируя активацию JAK-STAT сигнального пути. Проанализирован ряд исследований, в которых рассмотрен паттерн изменения концентрации IFNγ в сыворотке при SARS-CoV-2 и других вирусных инфекциях. Выполнен системный анализ результатов исследований, в которых была установлена закономерность между высокими концентрациями IFNγ и тяжелым течением COVID-19. Выявленные статистически достоверные высокие уровни IFNγ у пациентов с COVID-19 в ряде исследований чаще ассоциированы с неблагоприятным исходом заболевания. Приведены данные исследований в которых установлено, что значение медианы концентрации IFNγ у тяжелых пациентов с COVID-19 значительно выше по сравнению с результатами, полученными у пациентов средней тяжести, и возрастает по мере увеличения вирусной нагрузки в носоглотке и ухудшения состояния пациента.

Опираясь на данные о снижении концентрации IFNγ у выздоравливающих пациентов с COVID-19, рассмотрен механизм антагонизма IFNγ и IL-4, в котором снижающиеся сывороточные концентрации IFNγ и возрастающий уровень IL-4 могут являться косвенным критерием становления нормального адаптивного иммунного ответа с последующей выработкой антител к SARS-CoV-2 и постепенной элиминации вируса из организма. Приведены данные исследований в ходе которых обнаружено, что наличие у пациентов паразитарных инфекций вызванных Toxoplasma gondii, Cryptosporidium, Blastocystis hominis, Giardia duodenalis, Entamoeba histolytica и стойкий повышенный уровень IFNγ снижает риск тяжелого течения COVID-19.

To date, there is no consensus explaining the relationship between varying concentrations of IFNγ and the severity of infection caused by SARS-CoV-2. The aim of this article was to analyze and formulate conclusions from the selected studies and publications, which, in sum, provide a potentially reasonable view on the role of IFNγ in COVID-19 pathogenesis. This article highlights current data on the immunological role of IFNγ which affects differentiation of naive T helper cells, acting as a polarizing factor. It activates the major histocompatibility complex (MHC) class I and II, by increasing the expression of MHC I/II subunits, inhibiting replication of the viral particles by initiating activation of interferon-stimulated genes followed by subsequent synthesis of antiviral proteins. Moreover, IFNγ activates the production of cytokines by T cells, enhancing cytotoxic activity of the T killers. IFNγ exerts immunostimulatory and immunomodulatory effects via STAT1, SOCS1 and PIAS genes, thus regulating activation of the JAK-STAT signaling pathway. A number of studies were considered where the patterns of changes in serum IFNγ concentration were examined in viral infections and SARS-CoV-2. We performed a systemic analysis of the results of studies that showed a relationship between high concentrations of IFNγ and COVID-19 severity. In a number of studies, the significantly high levels of IFNγ in COVID-19 patients were often associated with a poor outcome of the disease. The median values of the IFNγ concentration in severe COVID-19 were found to be significantly higher compared to the results obtained in the cases of moderate severity. It shows an increase, in parallel with viral load in the nasopharyngeal samples upon worsening of the clinical condition. Based on the data on the decreased IFNγ concentrations in convalescent patients, the mechanism of antagonism between IFNγ and IL-4 is considered, where the decreases serum concentrations of IFNγ along with increasing level of IL-4 may be an indirect proof of normal adaptive immune response with subsequent development of antibodies to SARS-CoV-2 and gradual elimination of the virus from the body. Moreover, the evidence is discussed that the patients harboring some parasitic infections (Toxoplasma gondii, Cryptosporidium, Blastocystis hominis, Giardia duodenalis, Entamoeba histolytica) with persistently elevated level of IFNγ are at reduced risk for severe course of COVID-19.

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