medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2023-056medsovet-7444Research ArticleИММУНОЛОГИЯIMMUNOLOGYНовый взгляд на этиологию и иммунологические аспекты пневмонииModern view on the etiology and immunological aspects of pneumoniahttps://orcid.org/0000-0003-1525-3601МинаковА. А.MinakovA. A.

Минаков Алексей Александрович - адъюнкт 1-й кафедры (терапии усовершенствования врачей) имени академика Н.С. Молчанова.

194044, Санкт-Петербург, ул. Академика Лебедева, д. 6

Alexey A. Minakov - Adjunct of the 1st Department (Advanced Physician Therapy) named after Academician N.S. Molchanov, Military Medical Academy named after S.M. Kirov.

6, Akademik Lebedev St., St Petersburg, 194044

minakom@mail.ruhttps://orcid.org/0000-0001-5699-2414ВахлевскийВ. В.VakhlevskiiV. V.

Вахлевский Виталий Васильевич - адъюнкт кафедры факультетской терапии имени С.П. Боткина.

194044, Санкт-Петербург, ул. Академика Лебедева, д. 6

Vitalii V. Vakhlevskii - Adjunct of the Department of Faculty Therapy named after S.P. Botkin, Military Medical Academy named after S.M. Kirov.

6, Akademik Lebedev St., St Petersburg, 194044

vahlewsky@yandex.ruhttps://orcid.org/0000-0002-3880-9548ВолошинН. И.VoloshinN. I.

Волошин Никита Игоревич - адъюнкт 1-й кафедры (терапии усовершенствования врачей) имени академика Н.С. Молчанова.

194044, Санкт-Петербург, ул. Академика Лебедева, д. 6

Nikita I. Voloshin - Adjunct of the 1st Department (Advanced Physician Therapy) named after Academician N.S. Molchanov, Military Medical Academy named after S.M. Kirov.

6, Akademik Lebedev St., St Petersburg, 194044

nikitavoloshin1990@gmail.comhttps://orcid.org/0000-0002-6521-7986ХаритоновМ. A.KharitonovM. A.

Харитонов Михаил Анатольевич – доктор медицинских наук, профессор, профессор 1-й кафедры (терапии усовершенствования врачей) имени академика Н.С. Молчанова.

194044, Санкт-Петербург, ул. Академика Лебедева, д. 6

Mikhail A. Kharitonov - Dr. Sci. (Med.), Professor of the 1st Department and Clinic (Advanced Physician Therapy) named after Academician N.S. Molchanov - Military Medical Academy named after S.M. Kirov.

6, Akademik Lebedev St., St Petersburg, 194044

micjul11@yandex.ruhttps://orcid.org/0000-0003-1851-0941СалуховВ. В.SalukhovV. V.

Салухов Владимир Владимирович - доктор медицинских наук, доцент, начальник 1-й кафедры и клиники (терапии усовершенствования врачей) имени академика Н.С. Молчанова.

194044, Санкт-Петербург, ул. Академика Лебедева, д. 6

Vladimir V. Salukhov - Dr. Sci. (Med.), Associate Professor, Head of the 1st Department and Clinic (Advanced Physician Therapy) named after Academician N.S. Molchanov, Military Medical Academy named after S.M. Kirov.

6, Akademik Lebedev St., St Petersburg, 194044

vlasaluk@yandex.ruhttps://orcid.org/0000-0002-0470-1109ТыренкоВ. В.TyrenkoV. V.

Тыренко Вадим Витальевич - доктор медицинских наук, профессор, начальник кафедры и клиники факультетской терапии имени С.П. Боткина.

194044, Санкт-Петербург, ул. Академика Лебедева, д. 6

Vadim V. Tyrenko - Dr. Sci. (Med.), Professor, Head of the Department of Faculty Therapy named after S.P. Botkin, Military Medical Academy named after S.M. Kirov.

6, Akademik Lebedev St., St Petersburg, 194044

vadim_tyrenko@mail.ruhttps://orcid.org/0000-0001-7914-6173РудаковЮ. В.RudakovYu. V.

Рудаков Юрий Викторович - кандидат медицинских наук, доцент 1-й кафедры (терапии усовершенствования врачей) имени академика Н.С. Молчанова.

194044, Санкт-Петербург, ул. Академика Лебедева, д. 6

Yuri V. Rudakov - Cand. Sci. (Med.), Associate Professor of the 1st Department and Clinic (Advanced Physician Therapy) named after Academician N.S. Molchanov, Military Medical Academy named after S.M. Kirov.

6, Akademik Lebedev St., St Petersburg, 194044

rudakov_yura@mail.ruhttps://orcid.org/0000-0001-7411-5845ВахлевскаяЕ. Н.VakhlevskayaE. N.

Вахлевская Евгения Николаевна - врач-невролог, заведующая неврологическим отделением.

190031, Санкт-Петербург, ул. Садовая, д. 3/5

Evgeniya N. Vakhlevskaya - neurologist, Head of the Neurological Department, Consultative and Diagnostic Polyclinic of the Leningrad Military District No. 104.

3/5, Sadovaya St., St Petersburg, 190031

a.e.n.6284@yandex.ruhttps://orcid.org/0000-0001-5525-4655АлехинаЕ. В.AlekhinaE. V.

Алехина Екатерина Владимировна - курсант факультета подготовки врачей для ВМФ.

194044, Санкт-Петербург, ул. Академика Лебедева, д. 6

Ekaterina V. Alekhina - Cadet of the Navy Medical Faculty, Military Medical Academy named after S.M. Kirov.

6, Akademik Lebedev St., St Petersburg, 194044

alekhina_ev00@mail.ruВоенно-медицинская академия имени С.М. КироваРоссияMilitary Medical Academy named after S.M. KirovRussian FederationКонсультативно-диагностическая поликлиника Ленинградского военного округа №104РоссияConsultative and Diagnostic Polyclinic of the Leningrad Military District No. 104Russian Federation20231304202304141153Copyright © Минаков А.А., Вахлевский В.В., Волошин Н.И., Харитонов М.A., Салухов В.В., Тыренко В.В., Рудаков Ю.В., Вахлевская Е.Н., Алехина Е.В., 20232023Минаков А.А., Вахлевский В.В., Волошин Н.И., Харитонов М.A., Салухов В.В., Тыренко В.В., Рудаков Ю.В., Вахлевская Е.Н., Алехина Е.В.Minakov A.A., Vakhlevskii V.V., Voloshin N.I., Kharitonov M.A., Salukhov V.V., Tyrenko V.V., Rudakov Y.V., Vakhlevskaya E.N., Alekhina E.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/7444

Пневмония является самой распространенной и смертельно опасной нозологией среди всех болезней органов дыхания, ассоциированной с микроорганизмами. Несмотря на достигнутые успехи в антибактериальной и противовирусной терапии, летальность по причине пневмонии не снижается. Стоит отметить, что сама проблема инфекционной патологии всегда обсуждалась лишь в узких кругах специалистов, что привело к ее недооценке, в т. ч. в период пандемии новой коронавирусной инфекции. В настоящее время научные возможности не достигли своего совершенства в этиологической диагностике пневмонии. Немалую озабоченность вызывает отсутствие в программе обучения врачей-терапевтов и пульмонологов разделов, посвященных иммунологии, и, как следствие, незнание большинством медицинских специалистов основ иммунного ответа при различных инфекционных заболеваниях, в частности различий иммунного ответа макроорганизма при вирусных и бактериальных инфекциях, стадий иммунного ответа, различий между врожденными и адаптивными иммунными реакциями, возможностей иммунокорригирующей терапии. Являясь последователями пульмонологической научной школы академика Н.С. Молчанова, в данном обзоре мы оценили взаимовлияние этиологических факторов и иммунных особенностей организма на течение и исходы пневмонии с учетом современных научных знаний. Сформулировано актуальное определение пневмонии, подробно освещены вопросы этиологии пневмонии с позиции микробиома легких, особенности иммунного ответа макроорганизма при вирусных и бактериальных пневмониях, неосновательность иммунной защиты и влияние на это коморбидности. Понимание процессов, которые приводят к нарушению респираторного микробиома, размножению патобионтов, присоединению полирезистентных патогенных микроорганизмов, и адекватная оценка реактивности макроорганизма будут способствовать разработке новых терапевтических подходов в лечении пневмоний.

Pneumonia is the most common and deadly nosology among all respiratory diseases associated with microorganisms. Despite advances in antibacterial and antiviral therapy, mortality due to pneumonia is not decreasing. It should be noted that the problem of infectious pathology has always been discussed only in narrow circles of specialists, which led to its underestimation, including during the pandemic of a new coronavirus infection. At present, scientific possibilities have not reached their perfection in the etiological diagnosis of pneumonia. Of no small concern is the lack of sections on immunology in the training program for general practitioners and pulmonologists and, as a result, the lack of knowledge by most medical specialists of the basics of the immune response in various infectious diseases, in particular, the differences in the immune response of a macroorganism in viral and bacterial infections, the stages of the immune response, differences between innate and adaptive immune responses, possibilities of immunocorrective therapy. Being followers  of the scientific school of pulmonology of academician N.S. Molchanov,  in this review, we evaluated the features of etiological factors and immune characteristics of the body on the course and out-comes of pneumonia, taking into account modern scientific knowledge. The current definition of pneumonia is formulated, the issues of the etiology of pneumonia from the perspective of the lung microbiome, the features of the immune response of the macroorganism in viral and bacterial pneumonia, the inconsistency of immune protection and the impact of comorbidity on this are covered in detail. Understanding the processes that lead to the disruption of the respiratory microbiome, the multiplication of pathobionts, the attachment of multiresistant microorganisms and the reactivity of the macroorganism will contribute to the development of new therapeutic approaches in the treatment of pneumonia.

пневмониямикробиом дыхательных путейэтиология пневмониииммунология пневмонииреактивность макроорганизмаpneumoniarespiratory microbiomeetiology of pneumoniaimmunology of pneumoniareactivity of macroorganismReferencesМолчанов Н.С. Клиника и лечение острых пневмоний. Л.; 1971. 295 с.Molchanov N.S. Clinic and treatment of acute pneumonia. Leningrad; 1971. 295 p. (In Russ.)Авдеев С.Н., Дехнич А.В., Зайцев А.А., Козлов Р.С., Рачина С.А., Руднов В.А. и др. Внебольничная пневмония у взрослых: клинические рекомендации. М.; 2021. 126 с. Режим доступа: https://www.antibiotic.ru/files/306/kr654.pdf.Avdeev S.N., Dekhnich A.V., Zaitsev A.A., Kozlov R.S., Rachina S.A., Rudnov V.A. et al. Clinical recommendations: community-acquired pneumonia in adults. Moscow; 2021. 126 p. (In Russ.) Available at: https://www.antibiotic.ru/files/306/kr654.pdf.Стома И.О. Микробиом в медицине. М.: ГЭОТАР-Медиа; 2020. 320 с. https://doi.org/10.33029/9704-5844-0-MIM-2020-1-320.Stoma I.O. The Microbiome in Medicine. Мoscow: GEOTAR-Media; 2020. 320 p. (In Russ.) https://doi.org/10.33029/9704-5844-0-MIM-2020-1-320.Bos L.D.J., Rylance J., Gordon S.B. The lung bacterial microbiome in community-acquired and nosocomial pneumonia. In: Cox M.J., Ege M.J., von Mutius E. (eds.). The Lung Microbiome (ERS Monograph). Sheffield, European Respiratory Society; 2019, pp. 188–194. https://doi.org/10.1183/2312508X.10016418.Bos L.D.J., Rylance J., Gordon S.B. The lung bacterial microbiome in community-acquired and nosocomial pneumonia. In: Cox M.J., Ege M.J., von Mutius E. (eds.). The Lung Microbiome (ERS Monograph). Sheffield, European Respiratory Society; 2019, pp. 188–194. https://doi.org/10.1183/2312508X.10016418.Стома И.О. Микробиом дыхательных путей. М.: ГЭОТАР-Медиа; 2023. 104 с.Stoma I.O. Microbiome of the respiratory tract. Moscow: GEOTAR-Media; 2023. 104 p. (In Russ.)Харитонов М.А., Салухов В.В., Крюков Е.В., Паценко М.Б., Рудаков Ю.В., Богомолов А.Б. и др. Вирусные пневмонии: новый взгляд на старую проблему (обзор литературы). Медицинский совет. 2021;(16):60–77. https://doi.org/10.21518/2079-701X-2021-16-60-77.Kharitonov M.A., Salukhov V.V., Kryukov E.V., Patsenko M.B., Rudakov Yu.V., Bogomolov А.B. et al. Viral pneumonia: a new look at an old problem (review). Meditsinskiy Sovet. 2021;(16):60–77. (In Russ.) https://doi.org/10.21518/2079-701X-2021-16-60-77.Austrian R. The Gram stain and the etiology of lobar pneumonia, an historical note. Bacteriol Rev. 1960;24(3):261–265. https://doi.org/10.1128/br.24.3.261-265.1960.Austrian R. The Gram stain and the etiology of lobar pneumonia, an historical note. Bacteriol Rev. 1960;24(3):261–265. https://doi.org/10.1128/br.24.3.261-265.1960.Тяпкина Д.А., Бородай А.А., Тяпаева А.Р., Семенова О.Н., Наумова Е.А. Лабораторно-инструментальная диагностика вирусных пневмоний (обзор). Саратовский научно-медицинский журнал. 2021;17(1):13–18. Режим доступа: https://ssmj.ru/2021/1/13.Tyapkina, D.A., Boroday A.A., Typayeva A.R., Semenova O.N., Naumova E.A. Laboratory and instrumental diagnostics of viral pneumonia (review). Saratov Journal of Medical Scientific Research. 2021;17(1):13–18. (In Russ.) Available at: https://ssmj.ru/2021/1/13.Яковенко О.Н., Кравченко Н.А. Особенности эпидемиологии внебольничных пневмоний. Сибирский медицинский журнал (Иркутск). 2014;125(2):8–11. Режим доступа:https://cyberleninka.ru/article/n/osobennosti-epidemiologii-vnebolnichnyh-pnevmoniy.Yakovenko O.N., Kravchenko N.A. Epidemiology features of community-acquired pneumonia. Siberian Medical Journal (Irkutsk). 2014;125(2):8–11. (In Russ.) Available at: https://cyberleninka.ru/article/n/osobennosti-epidemiologii-vnebolnichnyh-pnevmoniy.Мороз В.В., Голубев А.М., Кузовлев А.Н. Нозокомиальная пневмония. Избранные вопросы диагностики и лечения. М.: Креативная экономика; 2019. 238 с. https://doi.org/10.18334/9785912922930.Moroz V.V., Golubev A.M., Kuzovlev A.N. Nosocomial pneumonia. Selected issues in diagnosis and treatment. Moscow: Kreativnaya ekonomika; 2019; 238 p. (In Russ.) https://doi.org/10.18334/9785912922930.Чучалин А.Г., Синопальников А.И., Страчунский Л.С., Козлов Р.С., Руднов В.А., Яковлев С.В. и др. Нозокомиальная пневмония у взрослых: практические рекомендации по диагностике, лечению и профилактике. Пособие для врачей. Пульмонология. 2005;(3):13–36. https://doi.org/10.18093/0869-0189-2005-0-3-13-36.Chuchalin A.G., Sinopalnikov A.I., Strachunsky L.S., Kozlov R.S., Rudnov V.A., Yakovlev S.V. et al. Nosocomial pneumonia in adults: practical recommendations on diagnosis, treatment and prevention. Medical supplementation. Pulmonologiya. 2005;(3):13–36. (In Russ.) https://doi.org/10.18093/0869-0189-2005-0-3-13-36.Hong H.L., Hong S.B., Ko G.B., Huh J.W., Sung H., Do K.H. et al. Viral infection is not uncommon in adult patients with severe hospital-acquired pneumonia. PLoS ONE. 2014;9(4):e95865. https://doi.org/10.1371/journal.pone.0095865.Hong H.L., Hong S.B., Ko G.B., Huh J.W., Sung H., Do K.H. et al. Viral infection is not uncommon in adult patients with severe hospital-acquired pneumonia. PLoS ONE. 2014;9(4):e95865. https://doi.org/10.1371/journal.pone.0095865.Dandachi D., Rodriguez-Barradas M.C. Viral pneumonia: etiologies and treatment. J Investig Med. 2018;66(6):957–965. https://doi.org/10.1136/jim-2018-000712.Dandachi D., Rodriguez-Barradas M.C. Viral pneumonia: etiologies and treatment. J Investig Med. 2018;66(6):957–965. https://doi.org/10.1136/jim-2018-000712.Глинчиков В.И. Клиника испанской болезни (из лекций, читаемых студентам Военно-медицинской академии и Государственного института медицинских знаний в 1919–1920 гг.). М., Петроград: Государственное издательство; 1922. 78 с.Glinchikov V.I. Clinic of Spanish disease (From lectures given to students of the Military Medical Academy and the State Institute of Medical Knowledge in 1919–1920). Moscow, Petrograd: Gosudarstvennoe izdatelstvo; 1922. 78 p. (In Russ.)Palacios G., Hornig M., Cisterna D., Savji N., Bussetti A.V., Kapoor V. et al. Streptococcus pneumoniae coinfection is correlated with the severity of H1N1 pandemic influenza. PLoS ONE. 2009;4(12):e8540. https://doi.org/10.1371/journal.pone.0008540.Palacios G., Hornig M., Cisterna D., Savji N., Bussetti A.V., Kapoor V. et al. Streptococcus pneumoniae coinfection is correlated with the severity of H1N1 pandemic influenza. PLoS ONE. 2009;4(12):e8540. https://doi.org/10.1371/journal.pone.0008540.Randolph A.G., Vaughn F., Sullivan R., Rubinson L., Thompson B.T., Yoon G. et al. Critically ill children during the 2009–2010 influenza pandemic in the United States. Pediatrics. 2011;128(6):e1450-1458. https://doi.org/10.1542/peds.2011-0774.Randolph A.G., Vaughn F., Sullivan R., Rubinson L., Thompson B.T., Yoon G. et al. Critically ill children during the 2009–2010 influenza pandemic in the United States. Pediatrics. 2011;128(6):e1450-1458. https://doi.org/10.1542/peds.2011-0774.Авдеев С.Н., Адамян Л.В., Алексеева Е.И., Багненко С.Ф., Баранов А.А., Баранова Н.Н. и др. Временные методические рекомендации: профилактика, диагностика и лечение новой коронавирусной инфекции (COVID-19) (версия 17). М.; 2022. 260 с. Режим доступа: https://www.consultant.ru/document/cons_doc_LAW_347896/?ysclid=ldh4z9qlmc823781520.Avdeev S.N., Adamyan L.V., Alexeyeva E.I., Bagnenko S.F., Baranov A.A., Baranova N.N. et al. Temporary methodological recommendations: prevention, diagnosis and treatment of a new coronavirus infection (COVID-19) (version 17). Moscow; 2022. 260 p. (In Russ.) Available at: https://www.consultant.ru/document/cons_doc_LAW_347896/?ysclid=ldh4z9qlmc823781520.Linscheid P., Seboek D., Nylen E.S., Langer I., Schlatter M., Becker K.L. et al. In vitro and in vivo calcitonin I gene expression in parenchymal cells: a novel product of human adipose tissue. Endocrinology. 2003;144(12):5578–5584. https://doi.org/10.1210/en.2003-0854.Linscheid P., Seboek D., Nylen E.S., Langer I., Schlatter M., Becker K.L. et al. In vitro and in vivo calcitonin I gene expression in parenchymal cells: a novel product of human adipose tissue. Endocrinology. 2003;144(12):5578–5584. https://doi.org/10.1210/en.2003-0854.Rodriguez-Morales A., Cardona-Ospina J.A., Gutierrez-Ocampo E., Villamizar-Pena R., Holguin-Rivera Y., Escalera-Antezana J.P. et al. Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis. Travel Med Infect Dis. 2020;34:1016–1023. https://doi.org/10.1016/j.tmaid.2020.101623.Rodriguez-Morales A., Cardona-Ospina J.A., Gutierrez-Ocampo E., Villamizar-Pena R., Holguin-Rivera Y., Escalera-Antezana J.P. et al. Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis. Travel Med Infect Dis. 2020;34:1016–1023. https://doi.org/10.1016/j.tmaid.2020.101623.Lansbury L., Lim B., Baskaran V., Lim W.S. Co-infections in people with COVID-19: a systematic review and meta-analysis. J Infect. 2020;81(2):266–275. https://doi.org/10.1016/j.jinf.2020.05.046.Lansbury L., Lim B., Baskaran V., Lim W.S. Co-infections in people with COVID-19: a systematic review and meta-analysis. J Infect. 2020;81(2):266–275. https://doi.org/10.1016/j.jinf.2020.05.046.Baskaran V., Lawrence H., Lansbury L.E., Webb K., Safavi S., Zainuddin N.I., Huq T. et al. Co-infection in critically ill patients with COVID-19: an observational cohort study from England. J Med Microbiol. 2021;70(4):001350. https://doi.org/10.1099/jmm.0.001350.Baskaran V., Lawrence H., Lansbury L.E., Webb K., Safavi S., Zainuddin N.I., Huq T. et al. Co-infection in critically ill patients with COVID-19: an observational cohort study from England. J Med Microbiol. 2021;70(4):001350. https://doi.org/10.1099/jmm.0.001350.Sharifipour E., Shams S., Esmkhani M., Khodadadi J., Fotouhi-Ardakani R., Koohpaei A. et al. Evaluation of bacterial co-infections of the respiratory tract in COVID-19 patients admitted to ICU. BMC Infect Dis. 2020;20(1):646. https://doi.org/10.1186/s12879-020-05374-z.Sharifipour E., Shams S., Esmkhani M., Khodadadi J., Fotouhi-Ardakani R., Koohpaei A. et al. Evaluation of bacterial co-infections of the respiratory tract in COVID-19 patients admitted to ICU. BMC Infect Dis. 2020;20(1):646. https://doi.org/10.1186/s12879-020-05374-z.Розанова С.М., Кырф М.В., Перевалова Е.Ю., Шевелева Л.В., Оленькова О.М., Бейкин Я.Б. Вторичная бактериальная пневмония у пациентов с COVID19: распространение и этиология. Клиническая микробиология и антимикробная химиотерапия. 2021;23(1):34–35. Режим доступа: https://www.antibiotic.ru/files/413/xxiii-makmah-tezisy.pdf.Rozanova S.M., Korf M.V., Perevalova E.Yu., Sheveleva L.V., Oleinikova O.M., Beikin Ya.B. Secondary bacterial pneumonia in patients with COVID19: distribution and etiology. Klinicheskaia Mikrobiologiia i Antimikrobnaia Khimioterapiia. 2021;23(1):34–35. (In Russ.) Available at: https://www.antibiotic.ru/files/413/xxiii-makmah-tezisy.pdf.Максимова Е.А., Козлов А.В., Лямин А.В., Жестков А.В., Гусякова О.А., Золотов М.О. Микрофлора мокроты и аутопсийного материала пациентов с COVID-19. Клиническая лабораторная диагностика. 2022;67(6):380-384. https://doi.org/10.51620/0869-2084-2022-67-6-380-384.Maksimova E.A., Kozlov A.V., Lyamin A.V., Zhestkov A.V., Gusyakova O.A., Zolotov M.O. Microflora of sputum and autopsy material of patients with COVID-19. Klinichescheskaya Laboratornaya Diagnostika. 2022;67(6):380–384. (In Russ.) Available at: https://doi.org/10.51620/0869-2084-2022-67-6-380-384.Jia L., Xie J., Zhao J., Cao D., Liang Y., Hou X. et al. Mechanisms of Severe Mortality-Associated Bacterial Co-infections Following Influenza Virus Infection. Front Cell Infect Microbiol. 2017;7:338. https://doi.org/10.3389/fcimb.2017.00338.Jia L., Xie J., Zhao J., Cao D., Liang Y., Hou X. et al. Mechanisms of Severe Mortality-Associated Bacterial Co-infections Following Influenza Virus Infection. Front Cell Infect Microbiol. 2017;7:338. https://doi.org/10.3389/fcimb.2017.00338.Lee L.N., Dias P., Han D., Yoon S., Shea A., Zakharov V. et al. A mouse model of lethal synergism between influenza virus and Haemophilus influenzae. Am J Pathol. 2010;176(2):800–811. https://doi.org/10.2353/ajpath.2010.090596.Lee L.N., Dias P., Han D., Yoon S., Shea A., Zakharov V. et al. A mouse model of lethal synergism between influenza virus and Haemophilus influenzae. Am J Pathol. 2010;176(2):800–811. https://doi.org/10.2353/ajpath.2010.090596.Егоров А. Проблема бактериальных осложнений при респираторных вирусных инфекциях. Microbiology Independent Research Journal (MIR Journal). 2018;5(1):1–11. https://doi.org/10.18527/2500-2236-2018-5-1-1-11.Egorov A. The problem of bacterial complications post respiratory viral infections. Microbiology Independent Research Journal (MIR Journal). 2018;5(1):1–11. (In Russ.) https://doi.org/10.18527/2500-2236-2018-5-1-1-11.Круглякова Л.В., Нарышкина С.В., Одиреев А.Н. Cовременные аспекты внебольничной пневмонии. Бюллетень физиологии и патологии дыхания. 2019;(71):120–134. https://doi.org/10.12737/article_5c89acc410e1f3.79881136.Kruglyakova L.V., Naryshkina S.V., Odireev A.N. Modern aspects of community-acquired pneumonia. Bulletin Physiology and Pathology of Respiration. 2019;(71):120–134. (In Russ.) https://doi.org/10.12737/article_5c89ac-c410e1f3.79881136.Jung H.S., Kang B.J., Ra S.W., Seo K.W., Jegal Y., Jun J.B. et al. Elucidation of Bacterial Pneumonia-Causing Pathogens in Patients with Respiratory Viral Infection. Tuberc Respir Dis (Seoul). 2017;80(4):358–367. https://doi.org/10.4046/trd.2017.0044.r.Jung H.S., Kang B.J., Ra S.W., Seo K.W., Jegal Y., Jun J.B. et al. Elucidation of Bacterial Pneumonia-Causing Pathogens in Patients with Respiratory Viral Infection. Tuberc Respir Dis (Seoul). 2017;80(4):358–367. https://doi.org/10.4046/trd.2017.0044.r.Cruveilhier L. Action du serum antipneumococcique au cours de la pneumonie et dans les complications de la grippe. Annales de l’Institut Pasteur. 1919;33:448–461.Cruveilhier L. Action du serum antipneumococcique au cours de la pneumonie et dans les complications de la grippe. Annales de l’Institut Pasteur. 1919;33:448–461.Rabst R., Tschernig T. Perivascular capillaries in the lung: an important but neglected vascular bed in immune reactions? J Allergy Clin Immunol. 2002;110(2):209–214. https://doi.org/10.1067/mai.2002.126836.Rabst R., Tschernig T. Perivascular capillaries in the lung: an important but neglected vascular bed in immune reactions? J Allergy Clin Immunol. 2002;110(2):209–214. https://doi.org/10.1067/mai.2002.126836.Qiu H., Kuolee R., Harris G., Harris G., Rooijen N.V., Patel G.B., Chen W. Role of macrophages in early host resistance to respiratory Acinetobacter baumannii infection. PLoS ONE. 2012;7(6):е40019. https://doi.org/10.1371/journal.pone.0040019.Qiu H., Kuolee R., Harris G., Harris G., Rooijen N.V., Patel G.B., Chen W. Role of macrophages in early host resistance to respiratory Acinetobacter baumannii infection. PLoS ONE. 2012;7(6):е40019. https://doi.org/10.1371/journal.pone.0040019.Hartl D., Tirouvanziam R., Laval J., Greene C.M., Habiel D., Sharma L. et al. Innate Immunity of the Lung: From Basic Mechanisms to Translational Medicine. J Innate Immun. 2018;10(5–6):487–501. https://doi.org/10.1159/000487057.Hartl D., Tirouvanziam R., Laval J., Greene C.M., Habiel D., Sharma L. et al. Innate Immunity of the Lung: From Basic Mechanisms to Translational Medicine. J Innate Immun. 2018;10(5–6):487–501. https://doi.org/10.1159/000487057.Kawai T., Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol. 2010;11(5):373–384. https://doi.org/10.1038/ni.1863.Kawai T., Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol. 2010;11(5):373–384. https://doi.org/10.1038/ni.1863.xO`Neill L.A.J., Fitzgerald K.A., Bowie A.G. The Toll-IL-1 receptor adaptor family grows to five members. Trends Immunol. 2003;24(6):286–289. https://doi.org/10.1016/s1471-4906(03)00115-7.xO`Neill L.A.J., Fitzgerald K.A., Bowie A.G. The Toll-IL-1 receptor adaptor family grows to five members. Trends Immunol. 2003;24(6):286–289. https://doi.org/10.1016/s1471-4906(03)00115-7.Peng J., Yuan Q., Lin B., Panneerselvam P., Wang X., Luan X.L. et al. SARM inhibits both TRIF – and MyD88-mediated AP-1 activation. Eur J Immunol. 2010;40(6):1738–1747. https://doi.org/10.1002/eji.200940034.Peng J., Yuan Q., Lin B., Panneerselvam P., Wang X., Luan X.L. et al. SARM inhibits both TRIF – and MyD88-mediated AP-1 activation. Eur J Immunol. 2010;40(6):1738–1747. https://doi.org/10.1002/eji.200940034.Kawai T., Akira S. Signaling to NF-kB by Toll-like receptors. Trends Mol Med. 2007;13(11):460–469. https://doi.org/10.1016/j.molmed.2007.09.002.Kawai T., Akira S. Signaling to NF-kB by Toll-like receptors. Trends Mol Med. 2007;13(11):460–469. https://doi.org/10.1016/j.molmed.2007.09.002.Negishi H., Fujita Y., Yanai H., Sakaguchi S., Ouyang X., Shinohara M. et al. Evidence for licensing of IFN-gamma induced IFN regulatory factor 1 transcription factor by MyD88 in Toll-like receptordependent gene induction program. Proc Natl Acad Sci USA. 2006;103(41):15136–15141. https://doi.org/10.1073/pnas.0607181103.Negishi H., Fujita Y., Yanai H., Sakaguchi S., Ouyang X., Shinohara M. et al. Evidence for licensing of IFN-gamma induced IFN regulatory factor 1 transcription factor by MyD88 in Toll-like receptordependent gene induction program. Proc Natl Acad Sci USA. 2006;103(41):15136–15141. https://doi.org/10.1073/pnas.0607181103.Mellett M., Atzei P., Jackson R., Jackson R., O’Neil L.A., Moynagh P.N. Mal mediates TLR-induced activation of CREB and expression of IL-10. J Immunol. 2011;186(8):4925–4935. https://doi.org/10.4049/jimmunol.1002739.Mellett M., Atzei P., Jackson R., Jackson R., O’Neil L.A., Moynagh P.N. Mal mediates TLR-induced activation of CREB and expression of IL-10. J Immunol. 2011;186(8):4925–4935. https://doi.org/10.4049/jimmunol.1002739.Jones B.W., Means T.K., Heldwein K.A., Keen M.A., Hiil P.G., Belisle J.T., Fenton M.J. Different Toll-like receptor agonists induce distinct macrophage responses. J Leukoc Biol. 2001;69(6):1036–1044. Available at: https://pubmed.ncbi.nlm.nih.gov/11404392.Jones B.W., Means T.K., Heldwein K.A., Keen M.A., Hiil P.G., Belisle J.T., Fenton M.J. Different Toll-like receptor agonists induce distinct macrophage responses. J Leukoc Biol. 2001;69(6):1036–1044. Available at: https://pubmed.ncbi.nlm.nih.gov/11404392.Dinarello C.A., Simon A., van der Meer J.W. Treating infl ammation by blocking interleukin-1 in broad spectrum of diseases. Nat Rev Drug Discov. 2012;11(8):633–652. https://doi.org/10.1038/nrd3800.Dinarello C.A., Simon A., van der Meer J.W. Treating infl ammation by blocking interleukin-1 in broad spectrum of diseases. Nat Rev Drug Discov. 2012;11(8):633–652. https://doi.org/10.1038/nrd3800.Wajant H., Pfizenmaier K., Scheurich P. Tumor necrosis factor signaling. Cell Death Differ. 2003;10:45–65. https://doi.org/10.1038/sj.cdd.4401189.Wajant H., Pfizenmaier K., Scheurich P. Tumor necrosis factor signaling. Cell Death Differ. 2003;10:45–65. https://doi.org/10.1038/sj.cdd.4401189.Swiecki M., Colonna M. The multifaceted biology of plasmacytoid dendritic cells. Nat Rev Immunol. 2015;15:471–485. https://doi.org/10.1038/nri3865.Swiecki M., Colonna M. The multifaceted biology of plasmacytoid dendritic cells. Nat Rev Immunol. 2015;15:471–485. https://doi.org/10.1038/nri3865.Olson B.M., Sullivan J.A., Burlingham W.J. Interleukin 35: a key mediator of suppression and the propagation of infectious tolerance. Front Immunol. 2013;4:315. https://doi.org/10.3389/fimmu.2013.00315.Olson B.M., Sullivan J.A., Burlingham W.J. Interleukin 35: a key mediator of suppression and the propagation of infectious tolerance. Front Immunol. 2013;4:315. https://doi.org/10.3389/fimmu.2013.00315.Conti H., Gaffen S. IL – 17 mediated immunity to the opportunistic fungal pathogen Candida albicans. J Immunol. 2015;195:780–788. https://doi.org/10.3389/fimmu.2013.00315.Conti H., Gaffen S. IL – 17 mediated immunity to the opportunistic fungal pathogen Candida albicans. J Immunol. 2015;195:780–788. https://doi.org/10.3389/fimmu.2013.00315.Xue J., Schmidt S., Sander J., Draffenh A., Krebs W., Quester I. et al. Transcriptome – based network analysis reveals a spectrum model of humanm macrophages activation. Immunity. 2014;40:274–288. https://doi.org/10.1016/j.immuni.2014.01.006.Xue J., Schmidt S., Sander J., Draffenh A., Krebs W., Quester I. et al. Transcriptome – based network analysis reveals a spectrum model of humanm macrophages activation. Immunity. 2014;40:274–288. https://doi.org/10.1016/j.immuni.2014.01.006.Von Lanzenauer S.H., Wolk K., Hoflich C., Kunz S., Grunberg B.H., Docke W.-D. et al. Interleukin-10 receptor-1 expression in monocyte-derived antigen-presenting cell populations: dendritic cells partially escape from IL-10`s inhibitory mechanisms. Genes Immunity. 2015;16:8–14. https://doi.org/10.1038/gene.2014.69.Von Lanzenauer S.H., Wolk K., Hoflich C., Kunz S., Grunberg B.H., Docke W.-D. et al. Interleukin-10 receptor-1 expression in monocyte-derived antigen-presenting cell populations: dendritic cells partially escape from IL-10`s inhibitory mechanisms. Genes Immunity. 2015;16:8–14. https://doi.org/10.1038/gene.2014.69.Хаитов Р.М. Иммунология: структура и функции иммунной системы. М.: ГЭОТАР-Медиа; 2013. 280 с.Khaitov R.M. Immunology: structure and functions of the immune system: acquired state. Moscow: GEOTAR-Media; 2013. 280 p. (In Russ.)Kallies A., Good-Jacobson K. Transcription Factor T-bet Orchestrates Lineage Development and Function in the Immune System. Trends Immunol. 2017;38:287–297. https://doi.org/10.1016/j.it.2017.02.003.Kallies A., Good-Jacobson K. Transcription Factor T-bet Orchestrates Lineage Development and Function in the Immune System. Trends Immunol. 2017;38:287–297. https://doi.org/10.1016/j.it.2017.02.003.Nakayama T., Hirahara K., Onodera A., Endo Y., Hosokawa H., Shinoda K. et al. Th2 Cells in Health and Disease. Annu Rev Immunol. 2016;35:53–84. https://doi.org/10.1146/annurev-immunol-051116-052350.Nakayama T., Hirahara K., Onodera A., Endo Y., Hosokawa H., Shinoda K. et al. Th2 Cells in Health and Disease. Annu Rev Immunol. 2016;35:53–84. https://doi.org/10.1146/annurev-immunol-051116-052350.Симбирцев А.С. Цитокины в патогенезе и лечении заболеваний человека. СПб.: Фолиант; 2018. 512 с. Режим доступа: https://znanium.com/catalog/document?id=350313&ysclid=lf9f8jzzb2398418280#ant.Simbirtsev A.S. Cytokines in the pathogenesis and treatment of human diseases. St Petersburg: Foliant; 2018. 512 p. (In Russ.) Available at: https://znanium.com/catalog/document?id=350313&ysclid=lf9f8jzz-b2398418280#ant.Kovarik P., Castiglia V., Ivin M., Ebner F. Type I Interferons in Bacterial Infections: A Balancing Act. Front Immunol. 2016;7:652. https://doi.org/10.3389/fimmu.2016.00652.Kovarik P., Castiglia V., Ivin M., Ebner F. Type I Interferons in Bacterial Infections: A Balancing Act. Front Immunol. 2016;7:652. https://doi.org/10.3389/fimmu.2016.00652.Subramanian K., Neill D.R., Malak H.A., Spelmink L., Khandaker S., Marchiori G.D.L. Pneumolysin binds to the mannose receptor C type 1 (MRC‐1) leading to anti‐inflammatory responses and enhanced pneumococcal survival. Nature Microbiology. 2019;4(1):62–70. https://doi.org/10.1038/s41564-018-0280-x.Subramanian K., Neill D.R., Malak H.A., Spelmink L., Khandaker S., Marchiori G.D.L. Pneumolysin binds to the mannose receptor C type 1 (MRC‐1) leading to anti‐inflammatory responses and enhanced pneumococcal survival. Nature Microbiology. 2019;4(1):62–70. https://doi.org/10.1038/s41564-018-0280-x.Duffaut C., Zakaroff-Girard A., Bourlier V., Decaunes P., Maumus M., Chiotasso P. et al. Interplay between human adipocytes and T lymphocytes in obesity: CCL20 as an adipochemokine and T lymphocytes as lipogenic modulators. Arterioscler Thromb Vasc Biol. 2009;29:1608–1614. https://doi.org/10.1161/ATVBAHA.109.192583.Duffaut C., Zakaroff-Girard A., Bourlier V., Decaunes P., Maumus M., Chiotasso P. et al. Interplay between human adipocytes and T lymphocytes in obesity: CCL20 as an adipochemokine and T lymphocytes as lipogenic modulators. Arterioscler Thromb Vasc Biol. 2009;29:1608–1614. https://doi.org/10.1161/ATVBAHA.109.192583.Салухов В.В., Лопатин Я.Р., Минаков А.А. Адипсин – подводя масштабные итоги. Consilium Medicum. 2022;24(5):317–323. https://doi.org/10.26442/20751753.2022.5.201280.Salukhov V.V., Lopatin Ya.R., Minakov A.A. Adipsin – summing up large-scale results. Consilium Medicum. 2022;24(5):317–323. (In Russ.) https://doi.org/10.26442/20751753.2022.5.201280.Bermudez E.A., Rifai N., Buring J., Manson J.A.E., Ridker P.M. Interrelationships among circulating interleukin-6, C-reactive protein, and traditional cardiovascular risk factors in women. Arterioscler Thromb Vasc Biol. 2002;22(10):1668–1673. https://doi.org/10.1161/01.ATV.0000029781.31325.66.Bermudez E.A., Rifai N., Buring J., Manson J.A.E., Ridker P.M. Interrelationships among circulating interleukin-6, C-reactive protein, and traditional cardiovascular risk factors in women. Arterioscler Thromb Vasc Biol. 2002;22(10):1668–1673. https://doi.org/10.1161/01.ATV.0000029781.31325.66.Kirii H., Niwa T., Yamada Y., Wada H., Saito K., Iwakura Y. et al. Lack of Interleukin-1β decreases the severity of atherosclerosis in ApoE-deficient mice. Arterioscler Thromb Vasc Biol. 2003;23(4):656–660. https://doi.org/10.1161/01.ATV.0000064374.15232.C3.Kirii H., Niwa T., Yamada Y., Wada H., Saito K., Iwakura Y. et al. Lack of Interleukin-1β decreases the severity of atherosclerosis in ApoE-deficient mice. Arterioscler Thromb Vasc Biol. 2003;23(4):656–660. https://doi.org/10.1161/01.ATV.0000064374.15232.C3.Козлов В.К. Цитокинотерапия: патогенетическая направленность и клиническая эффективность при инфекционных заболеваниях. СПб.: Альтер Эго; 2010. 148 с.Kozlov V.K. Cytokinotherapy: pathogenetic orientation and clinical efficacy in infectious diseases. St Petersburg: Alter Ego; 2010. 148 p. (In Russ.)Ip W., Hoshi N., Shouval D., Snapper S., Medzhitov R. Anti-inflammatory effect of IL – 10 mediated by metabolic reprogramming of macrophages. Science. 2017;356:513–519. https://doi.org/10.1126/science.aal3535.Ip W., Hoshi N., Shouval D., Snapper S., Medzhitov R. Anti-inflammatory effect of IL – 10 mediated by metabolic reprogramming of macrophages. Science. 2017;356:513–519. https://doi.org/10.1126/science.aal3535.Семенов Б.Ф., Каулен Д.Р., Баландин И.Г. Клеточные и молекулярные основы противовирусного иммунитета. М.: Медицина; 1982. 240 с.Semenov B.F., Kaulen D.R., Balandin I.G. Cellular and molecular foundations of antiviral immunity. Moscow: Meditsina; 1982. 240 p. (In Russ.)Vilchek J. Recent progress in elucidation of interferons – α/β and interferon – γ actions. Semin Hematol. 1993;30:9–10. https://doi.org/10.1159/000236685.Vilchek J. Recent progress in elucidation of interferons – α/β and interferon – γ actions. Semin Hematol. 1993;30:9–10. https://doi.org/10.1159/000236685.Кассирский И.А. Вопросы клиники и терапии острых пневмоний. Острые пневмонии. М.: Медгиз; 1961. 201 с.Kassirsky I.A. Questions of the clinic and therapy of acute pneumonia. Acute pneumonia. Moscow: Medgiz; 1961. 201 p. (In Russ.)Horby P., Lim W.S., Emberson J.R., Mafham M., Bell J.L., Linsell L. et al. RECOVERY Collaborative Group. Dexamethasone in Hospitalized Patients with COVID-19. N Engl J Med. 2021;384(8):693–704. https://doi.org/10.1056/NEJMoa2021436.Horby P., Lim W.S., Emberson J.R., Mafham M., Bell J.L., Linsell L. et al. RECOVERY Collaborative Group. Dexamethasone in Hospitalized Patients with COVID-19. N Engl J Med. 2021;384(8):693–704. https://doi.org/10.1056/NEJMoa2021436.Чугунов А.А., Салухов В.В., Данцева О.В., Харитонов М.А., Рудаков Ю.В., Болехан А.В., Аржавкина Л.Г. Некоторые аспекты применения глюкокортикоидных препаратов в комплексном лечении новой коронавирусной инфекции. Медицинский альянс. 2021;9(1):43–51. Режим доступа: http://med-alyans.spbniif.ru/index.php/Hahn/article/view/708.Chugunov A.A., Salukhov V.V., Dontsova O.V., Kharitonov M.A., Rudakov Yu.V., Bolekhan A.V., Arzhavkina L.G. Some aspects of the use of glucocorticoid drugs in the complex treatment of a new coronavirus infection. Medical Alliance. 2021;9(1):43–51. (In Russ.) Available at: http://med-alyans.spbniif.ru/index.php/Hahn/article/view/708.Крюков Е.В., Салухов В.В., Котив Б.Н., Овчинников Д.В., Андрейчук Ю.В., Денисов Д.Г. и др. Факторы, влияющие на содержание IgG-антител к S-белку SARS-CoV-2 в крови у реконвалесцентов после новой коронавирусной инфекции (COVID-19). Медицинский совет. 2022;(4):51–65. https://doi.org/10.21518/2079-701X-2022-16-4-51-65.Kryukov E.V., Salukhov V.V., Kotiv B.N., Ovchinnikov D.V., Andreychuk Yu.V., Denisov D.G. et al. Factors affecting the content of Ig G-antibodies to S-protein SARS-CoV-2 in the blood of reconvalescents after new coronaviral infection (COVID-19). Meditsinskiy Sovet. 2022;(4):51–65. (In Russ.) https://doi.org/10.21518/2079-701X-2022-16-4-51-65.

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