Russian Journal of Infection and ImmunityRussian Journal of Infection and ImmunityИнфекция и иммунитет2220-76192313-7398SPb RAACI167010.15789/2220-7619-ACR-1670REVIEWSОБЗОРЫA controversial role of neutrophils in tuberculosis infection pathogenesisНейтрофилы: неоднозначная роль в патогенезе туберкулезаhttps://orcid.org/0000-0003-1535-5800LingeI. A.ЛингеИ. А.
Russian Federation

Irina A. Linge,  PhD (Biology), Senior Researcher, Laboratory of Immunogenetics, Immunology Department 

107564, Moscow, Yauzskaya alley, 2

Phone: +7 499 785-90-72 

Линге Ирина Андреевна,  к.б.н., старший научный сотрудник лаборатории иммуногенетики отдела иммунологии 

107564, Москва, Яузская аллея, 2,

Тел.: 8 499 785-90-72

iralinge@gmail.comhttps://orcid.org/0000-0002-3683-3085AptA. S.АптА. С.
Russian Federation

PhD, MD (Biology), Professor, Head of the Laboratory of Immunogenetics, Immunology Department 

Moscow

д.б.н., профессор, зав. лабораторией иммуногенетики отдела иммунологии 

Москва

alexapt0151@gmail.comCentral Tuberculosis Research InstituteФГБНУ Центральный НИИ туберкулеза211120211158098192201202116082021Copyright ©; 2021, Linge I.A., Apt A.S.Copyright ©; 2021, Линге И.А., Апт А.С.2021Linge I.A., Apt A.S.Линге И.А., Апт А.С.https://creativecommons.org/licenses/by/4.0https://iimmun.ru/iimm/article/view/1670

Tuberculosis (TB) continues to be an important and unresolved medical problem. About a quarter of mankind is infected with Mycobacterium tuberculosis, and about 5–10% of these people eventually develop TB. Macrophages and CD4+ T cells are considered the key cells providing defense against TB infection. The role of neutrophils in TB is less well defined. Neutrophils are short-lived granulocytes among first migrate into the infectious lung tissue and phagocy tose mycobacteria. On the one hand, there is evidence for protective role of neutrophils in TB released via anti-microbial peptides inhibiting mycobacterial growth, up-regulation of CD4+ T-cell activation, and dendritic cell migration in the lymph nodes. On the other hand, infection of genetically TB susceptible animals leads to an overwhelming lung neutrophil inflammation, development of necrotic granulomata, and a rapid death. Neutrophils act directly or indirectly on mycobacteria by different oxidative or other reactions including neutrophil extracellular traps (NETs) formation. Phagocytosis of mycobacteria by neutrophils is accompanied by the production of pro-inflammatory factors, thus making neutrophils active participants of inflammation in all stages of the infectious process. Finally, neutrophils die by apoptosis or necrosis. Necrosis of neutrophils, which is activated by reactive oxygen species, also prolongs the inflammation. In this way, there is strong evidence that neutrophils are the cells involved in the transition of infection to the terminal stage, participating in lung tissue destruction. Although neutrophils evolutionary developed many ways to resist pathogens, it is likely, that neutrophils do not possess sufficient anti-mycobactericidal capacities due to the development of many adaptations allowing mycobacteria to survive inside the neutrophils. Neutrophils effectively phagocytose but poorly kill mycobacteria, thus hiding bacilli from more efficient killers, macrophages, and playing the role of the “Trojan Horse”. In this review, we summarize the data on the involvement of neutrophils in TB inflammation. We discuss their ambiguous role in pathogenesis which depends upon mycobacterial virulence, host genetics, dynamics of migration to inflammatory foci, and persistence during initial and chronic stages of the infectious process.

Туберкулез (ТБ) до сих пор является важной нерешенной медицинской проблемой. Примерно четверть человечества заражена Mycobacterium tuberculosis, и у 5–10% рано или поздно развивается ТБ. Макрофаги и Т-лимфоциты CD4+ являются основными иммунными клетками, противостоящими ТБ-инфекции. Гораздо меньше известно о роли нейтрофилов при ТБ. Нейтрофилы, короткоживущие лейкоциты, в числе первых реагируют на проникновение инфекции, мигрируют в очаг воспаления и поглощают микобактерии в легких. С одной стороны, есть свидетельства защитной роли нейтрофилов за счет продукции пептидов, подавляющих рост микобактерий, усиления активации Т-лимфоцитов CD4+ и миграции дендритных клеток в лимфоузлы. С другой стороны, инфицирование генетически чувствительных к ТБ животных приводит к избыточному притоку нейтрофилов в легкие, формированию некротических гранулем и быстрой гибели. Нейтрофилы напрямую или опосредованно воздействуют на микобактерии, используя различные окислительные и неокислительные реакции, а также образуя нейтрофильные внеклеточные ловушки (NETs). Фагоцитоз микобактерий нейтрофилами стимулирует выделение ими множества провоспалительных медиаторов, поэтому нейтрофилы являются активными участниками воспаления на всех стадиях развития инфекционного процесса. В конечном итоге нейтрофилы погибают путем апоптоза или некроза. Гибель нейтрофилов путем некроза, инициируемого активными формами кислорода, в свою очередь также провоцирует излишнее воспаление. В связи с этим велика вероятность того, что именно нейтрофилы способствуют переходу ТБ в терминальную стадию, участвуя в распаде легочной ткани. Кроме того, несмотря на то что эволюционно нейтрофилы имеют достаточно возможностей воздействия на патоген, по-видимому, сами по себе они не обладают достаточной бактерицидной активностью в отношении микобактерий вследствие формирования у последних механизмов защиты, позволяющих выживать внутри клеток. Таким образом, нейтрофилы фагоцитируют, но не убивают микобактерии и могут выступать в роли «троянского коня», экранируя бактерии от более эффективных защитных действий макрофагов. В этом обзоре мы обобщаем данные последних лет об участии нейтрофилов в туберкулезном воспалении. Мы обсуждаем неоднозначность их роли в патогенезе в зависимости от вирулентости микобактерий и генетических особенностей хозяина, динамику притока нейтрофилов в очаг воспаления и персистирование в начальной и хронической стадиях инфекции.

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