Врожденный иммунитет при коронавирусной инфекции

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Инфекция и иммунитет. 2020; 10: 259-268

Врожденный иммунитет при коронавирусной инфекции

Смирнов В. С., Тотолян Арег А.

https://doi.org/10.15789/2220-7619-III-1440

Аннотация

Коронавирусы (CoV) представляют собой полиморфную группу респираторных вирусов, вызывающих острые воспалительные заболевания у домашних и сельскохозяйственных животных (куры, свиньи, буйволы, кошки, собаки). У людей инфекция до недавнего времени наблюдалось преимущественно в осенне-зимний период и характеризовалась легким, зачастую бессимптомным, течением. Ситуация резко изменилась в 2003 году, когда в Китае была зарегистрирована вспышка атипичной пневмонии, вызванная патогенным CoV (SARS-CoV). Спустя 10 лет возникла новая вспышка CoV в виде ближневосточного респираторного синдрома (MERS-CoV), а в декабре 2019 г. отмечены случаи SARS-CoV-2 (COVID-19), трансформировавшиеся в первые месяцы 2020 г. в пандемию. Во всех трех случаях заболевание часто приводило к тяжелыми бронхолегочными поражениями, варьировавшим от сухого изнурительного кашля до острого респираторного дистресс-синдрома (ОРДС). Одновременно с этим отмечены множественные изменения в системе врожденного иммунитета, чаще всего в виде выраженной воспалительной реакции в нижних дыхательных путях, проявлявшиеся повреждением пневмоцитов II порядка, явлениями апоптоза, гиалинизацией альвеолярных мембран, очаговым или генерализованным отеком легких. Деструктивные процессы в респираторном отделе сопровождались миграцией в очаг воспаления моноцитов/макрофагов и нейтрофильных гранулоцитов. На фоне перечисленных явлений наблюдалась выработка провоспалительных цитокинов, интенсивность которой могла нарастать до цитокинового шторма. Для SARS-CoV характерны симптомы вторичной иммунодепрессии, проявляющиеся в позднем начале синтеза интерферонов и активации ключевого фактора воспаления — NLRP3-инфламмасомы. Причиной подобной реакции является «вооруженность» CoV обширным набором структурных и неструктурных белков, обладающих провоспалительными и иммунодепрессивными свойствами. Отсроченный синтез IFN позволял вирусу активно и беспрепятственно реплицироваться, а когда все же организм запускал синтез IFN I, его действие оказывалось вредным и сопровождалось утяжелением течения инфекции. Таким образом, SARS можно с полным основанием отнести к числу иммунозависимых инфекций с выраженным иммунопатологическим компонентом. Цель этого обзора описать некоторые механизмы формирования врожденного иммунного ответа на инфицирование патогенными коронавирусами: SARS-CoV, MERS-CoV и SARS-CoV-2 (COVID-19).

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Russian Journal of Infection and Immunity. 2020; 10: 259-268

Innate immunity in coronavirus infection

Smirnov V. S., Totolyan Areg A.

https://doi.org/10.15789/2220-7619-III-1440

Abstract

Coronaviruses (CoVs) comprise a polymorphic group of respiratory viruses causing acute inflammatory diseases in domestic and agricultural animals (chicken, pig, buffalo, cat, dog). Until recently, this infection in humans was mainly observed during the autumn-winter period and characterized by a mild, often asymptomatic, course. The situation changed dramatically in 2003, when SARS outbreak caused by pathogenic CoV (SARS-CoV) was recorded in China. A decade later, a new CoV outbreak occurred in the form of the Middle East respiratory syndrome (MERS-CoV), whereas in December 2019, SARS-CoV-2 (COVID-19) cases were recorded, which transformed within the first months of 2020 into the pandemic. In all three cases, CoV disease led to severe bronchopulmonary lesions, varying from dry, debilitating cough to acute respiratory distress syndrome (ARDS). At the same time, multiple changes in innate immunity were noted most often manifested as a pronounced inflammatory reaction in the lower respiratory tract, featured by damaged type II pneumocytes, apoptosis, hyalinization of alveolar membranes, focal or generalized pulmonary edema. Destructive processes in the respiratory tract were accompanied by migration of monocytes/macrophages and granulocyte neutrophils to the inflammatory focus. Such events were accompanied by production of pro-inflammatory cytokines, which magnitude could ascend up to a cytokine storm. SARS-CoV is characterized by symptoms of secondary immunosuppression, manifested by the late onset of interferon production and activation of NLRP3 inflammasomes – the key inflammatory factor. The reason for such reaction may be accounted for by CoV arsenal containing extensive set of structural and non-structural proteins exerting pro-inflammatory and immunosuppressive properties. Delayed IFN production allowed CoV to replicate actively and freely, and when type I IFN synthesis was eventually triggered, its activity was detrimental and accompanied by an aggravated infection course. Thus, SARS can surely be referred to immune-dependent infections with a marked immunopathological component. The purpose of this review was to describe some mechanisms underlying formation of innate immune response to infection caused by pathogenic coronaviruses SARS-CoV, MERS-CoV and SARS-CoV-2 (COVID-19).

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