Нейтрофильные внеклеточные ловушки и туберкулез: патогенетическая роль и особенности формирования
https://doi.org/10.58838/2075-1230-2025-103-5-102-111
Аннотация
В обзоре приведен анализ 69 источников литературы, посвященных обсуждению механизмов формирования нейтрофильных внеклеточных ловушек при различных инфекционных и неинфекционных заболеваниях. Показаны особенности образования нейтрофильных внеклеточных ловушек при активном туберкулезе органов дыхания, их роль в патогенезе распространенных деструктивных форм заболевания. Приведены сведения о возрастных особенностях нетозоформирующей функции нейтрофилов при туберкулезной инфекции.
Ключевые слова
Об авторах
А. В. МордыкРоссия
Мордык Анна Владимировна - д. м. н., профессор, заведующий кафедрой фтизиатрии, пульмонологии и инфекционных болезней.
644099, Омск, ул. Ленина, д. 12
Тел.: +7 (3812) 95-70-01
О. Г. Иванова
Россия
Иванова Ольга Георгиевна - д. м. н., доцент, профессор кафедры фтизиатрии, пульмонологии и инфекционных болезней.
644099, Омск, ул. Ленина, д. 12
Тел.: +7 (3812) 95-70-01
А. Н. Золотов
Россия
Золотов Александр Николаевич - к. м. н., старший научный сотрудник центральной научно-исследовательской лаборатории.
644099, Омск, ул. Ленина, д. 12
Тел.: +7 (3812) 95-70-01
М. А. Романова
Россия
Романова Мария Алексеевна - к. м. н., доцент кафедры фтизиатрии, пульмонологии и инфекционных болезней.
644099, Омск, ул. Ленина, д. 12
Тел.: +7 (3812) 95-70-01
А. О. Птухин
Россия
Птухин Александр Олегович - аспирант кафедры фтизиатрии, пульмонологии и инфекционных болезней.
644099, Омск, ул. Ленина, д. 12
Тел.: +7 (3812) 95-70-01
Д. Г. Новиков
Россия
Новиков Дмитрий Георгиевич - к. м. н., заведующий центральной научно-исследовательской лабораторией.
644099, Омск, ул. Ленина, д. 12
Тел.: +7 (3812) 95-70-01
Список литературы
1. Воробьева Н.В., Черняк Б.В. НЕТоз: молекулярные механизмы, роль в физиологии и патологии // Биохимия. – 2020. – Т. 85, № 10. – С. 1383-1397.
2. Илиади В.А., Илиадис С.А., Константинидис Т.Г. Нейтрофильные внеклеточные ловушки // Modern Science. – 2020. – № 12. – С. 95-99.
3. Карнаушкина М.А., Гурьев А.С., Миронов К.О., Дунаева Е.А., Корчагин В.И., Бобкова А.Ю., Васильева И.С., Кассина Д.В., Литвинова М.М. Ассоциации полиморфизмов генов толл-подобных рецепторов и активности нетоза как проностические критерии тяжести течения пневмоний // Современные технологии в медицине. – 2021. – Т.13, № 3. – С. 47-54. https://doi.org/10.17691/stm2021.13.3.06
4. Линге И.А., Апт А.С. Нейтрофилы: неоднозначная роль в патогенезе туберкулеза // Инфекция и иммунитет. – 2021. – Т. 11, № 5. – C. 809-819. https://doi.org/10.15789/2220-7619-ACR-1670
5. Лотош Н.Ю., Алясева С.О., Василов Р.Г., Селищева А.А. Стериламин вызывает образование нейтрофильных внеклеточных ловушек независимо от активных форм кислорода // Цитология. – 2019. – Т. 61, № 4. – С. 308-318. https://doi.org/10.1134.S0041377119040035
6. Мордык А.В., Золотов А.Н., Новиков Д.Г., и др. Возрастные особенности формирования внеклеточных ловушек нейтрофилов у здоровых лиц и больных туберкулезом // Вестник современной клинической медицины. – 2023. – Т. 16, № 6. – С. 37-45. https://doi.org/10.20969/VSKM.2023.16(6).37-45.
7. Мордык А.В., Золотов А.Н., Новиков Д.Г., Кириченко Н.А., Пахтусова П.О., Птухин А.О. Нетозформирующая способность нейтрофилов у пациентов с ограниченным и распространенным туберкулезным процессом // Туберкулез и болезни легких. – 2023. – Т. 101, № 3. – С. 78-86. https://doi.org/10.58838/2075-1230-2023-101-3-78-86
8. Плескова С.Н., Горшкова Е.Н., Боряков А.В., Крюков Р.Н. Морфологические особенности быстрого и классического нетоза // Цитология. – 2019. – Т. 61, № 9. – С. 704-712.
9. Appelgren D., Enocsson H., Skogman B.H., et al. Neutrophil Extracellular Traps (NETs) in the Cerebrospinal Fluid Samples from Children and Adults with Central Nervous System Infections // Cells. – 2019. – Vol 9, № 1. – P. 43. https://doi.org/10.3390/cells9010043
10. Brinkmann V., Reichard U., Goosmann C., Fauler B., Uhlemann Y., Weiss D.S., et al. Neutrophil extracellular traps kill bacteria // Science. – 2004. – Vol. 303, № 5663 – P. 1532-1535. https://doi.org/10.1126/science.1092385
11. Brinkmann V., Zychlinsky A. Beneficial suicide: why neutrophils die to make NETs // Nat Rev Microbiol. – 2007. – Vol. 5, № 8. – P. 577-582. https://doi.org/10.1038/nrmicro1710
12. Brinkmann V., Zychlinsky A. Neutrophil extracellular traps: Is immunity the second function of chromatin? // J. Cell Biol. – 2012. – Vol. 198, № 5 – P. 773-783. https://doi.org/10/1083/jcb.201203170
13. Byrd A.S., O’Brien X.M., Johnson C.M., Lavigne L.M., Reichner J.S. An extracellular matrix-based mechanism of rapid neutrophil extracellular trap formation in response to Candida albicans // J Immunol. – 2013. – Vol. 190, № 8 – P. 4136-4148. https://doi.org/10.4049/jimmunol.1202671
14. Castillo E.F., Dekonenko A., Arko-Mensah J., Mandell M.A., Dupont N., Jiang S., Delgado-Vargas M., Timmins G.S., Bhattacharya D., Yang H., Hutt J., Lyons C.R., Dobos K.M., Deretic V. Autophagy protects against active tuberculosis by suppressing bacterial burden and inflammation // Proc. Natl. Acad. Sci. USA. – 2012. – Vol. 109, № 46. – Р. E3168-E3176. https://doi.org/10.1073/pnas.1210500109
15. Cheng O.Z., Palaniyar N. NET balancing: a problem in inflammatory lung diseases // Front Immunol. – 2013. – № 4. – P. 1. – https://doi.org/10.3389/fimmu.2013.00001
16. Colón D.F., Wanderley C.W., Franchin M., et al. Neutrophil extracellular traps (NETs) exacerbate severity of infant sepsis // Crit Care. – 2019. – Vol. 23, № 1. – P. 113. https://doi.org/10.1186/s13054-019-2407-8
17. Corleis B., Korbel D., Wilson R., Bylund J., Chee R., Schaible U.E. Escape of Mycobacterium tuberculosis from oxidative killing by neutrophils // Cell Microbiol. – 2012. – Vol. 14, № 7. – P.1109-1121. https://doi.org/10.1111/j.1462-5822.2012.01783.x
18. Dabrowska D., Jablonska E., Garley M., Ratajczak-Wrona W., Ivaniuk A. New aspects of the biology of neutrophil extracellular traps // Scand. J. Immunol. – 2016. – Vol. 84, № 6 – P. 317-322. https://doi.org/10.1111/sji.12494
19. Dallenga T., Repnik U., Corleis B., Eich J., Reimer R., Griffiths G.W., Schaible U.E. M. tuberculosis-induced necrosis of infected neutrophils promotes bacterial growth following phagocytosis by macrophages // Cell Host Microbe. – 2017. – Vol. 22, № 6 – P. 519. – Р. 519–530.e3. https://doi.org/10.1016/j.chom.2017.09.003
20. Dapino P., Dallegri F., Ottonello L., Sacchetti C. Induction of neutrophil respiratory burst by tumour necrosis factor-alpha; priming effect of solid-phase fibronectin and intervention of CD llb-CD18 integrins // Clin. Exp. Immunol. – 2008. – Vol. 94, № 3. – P. 533-538. https://doi.org/10.1111/j.1365-2249.1993.tb08230.x
21. DeLeo F.R. Modulation of phagocyte apoptosis by bacterial pathogens // Apoptosis. – 2004. – Vol. 9, № 4 – P. 399-413. https://doi.org/10.1023/B:APPT.0000031448.64969.fa
22. De Melo M.G.M., Mesquita E.D.D., Oliveira M.M., Silva-Monteiro C., Silveira A.K.A., Malaquias T.S., Dutra T.C.P., Galliez R.M., Kritski A.L., Silva E.C. Imbalance of NET and Alpha-1-Antitrypsin in Tuberculosis Patients Is Related With Hyper Inflammation and Severe Lung Tissue Damage // Front. Immunol. – 2019. – № 9. – Р. 3147. https://doi.org/10.3389/fimmu.2018.03147
23. Dorhoi A., Iannaccone M., Maertzdorf J., Nouailles G., Weiner J. 3rd, Kaufmann S.H. Reverse translation in tuberculosis: neutrophils provide clues for understanding development of active disease // Front Immunol. – 2014. – № 5. – P. 36. https://doi.org/10.3389/fimmu.2014.00036
24. Eum S.Y., Kong J.H., Hong M.S., Lee Y.J., Kim J.H., Hwang S.H., et al. Neutrophils are the predominant infected phagocytic cells in the airways of patients with active pulmonary TB // Chest. – 2010. – Vol. 137, № 1 – P. 122-128. https://doi.org/10.1378/chest.09-0903
25. Francis R.J., Butler R.E., Stewart G.R. Mycobacterium tuberculosis ESAT-6 is a leukocidin causing Ca2+ influx, necrosis and neutrophil extracellular trap formation // Cell Death Dis. – 2014. – Vol. 5, № 10. – Р. e1474. https:// doi.org/10.1038/cddis.2014.394
26. Fuchs T.A., Abed U., Goosmann C., Hurwitz R., Schulze I., Wahn V., et al. Novel cell death program leads to neutrophil extracellular traps // J Cell Biol. – 2007. – Vol. 176, № 2. – P. 231-241. https://doi.org/10.1083/jcb.200606027
27. Futosi K., Fodor S., Mócsai A. Reprint of neutrophil cell surface receptors and their intracellular signal transduction pathways // Int. Immunopharmacology. – 2013. – Vol. 17, № 4. – P. 1185-1197. https://doi.org/10.1016/j.intimp.2013.11.010
28. Gopal R., Monin L., Torres D., Slight S., Mehra S., McKenna K.C., et al. S100A8/ A9 proteins mediate neutrophilic inflammation and lung pathology during tuberculosis // Am J Respir Crit Care Med. – 2013. – Vol. 188, № 9. – P.1137-1146. https://doi.org/10.1164/rccm.201304-0803OC
29. Guimarães-Costa A.B., Nascimento M.T.C, Froment G., Soares R.P.P., Morgado F.N., Conceição-Silva F., et al. Leishmania amazonensis promastigotes induce and are killed by neutrophil extracellular traps // Proc Natl Acad Sci USA. – 2009. – Vol. 106, № 16 – P. 6748-6753. https://doi.org/10.1073/pnas.0900226106
30. Hollingsworth T.J., Radic M.Z., Beranova-Giorgianni S., et al. Murine Retinal Citrullination Declines With Age and is Mainly Dependent on Peptidyl Arginine Deiminase 4 (PAD4) // Invest Ophthalmol Vis Sci. – 2018. – Vol. 59, № 10. – P. 3808-3815. https://doi.org/10.1167/iovs.18-24118
31. Houben D., Demangel C., van Ingen J., Perez J., Baldeon L., Abdallah A.M., et al. ESX-1-mediated translocation to the cytosol controls virulence of mycobacteria // Cell Microbiol. – 2012. – Vol. 14, № 8. – P. 1287-1298. https://doi.org/10.1111/j.1462-5822.2012.01799.x
32. Jena P., Mohanty S., Mohanty T., Kallert S., Morgelin M., Lindstrøm T., Borregaard N., Stenger S., Sonawane A., Sørensen O.E. Azurophil granule proteins constitute the major mycobactericidal proteins in human neutrophils and enhance the killing of mycobacteria in macrophages // PLoS One. – 2012. – Vol. 7, № 12 – Р. e50345. https://doi.org/10.1371/journal.pone.005034
33. Jenne C.N., Wong C.H.Y., Zemp F.J., McDonald B., Rahman M.M., Forsyth P.A., et al. Neutrophils recruited to sites of infection protect from virus challenge by releasing neutrophil extracellular traps // Cell Host Microbe. – 2013. – Vol. 13, № 2. – P. 169-180. https://doi.org/10.1016/j.chom.2013.01.005
34. Jorch S.K., Kubes P. An emerging role for neutrophil extracellular traps in noninfectious disease // Nat Med. – 2017. – Vol. 23, № 3. – P.279-287. https://doi.org/10.1038/nm.4294
35. Kaplan M.J., Radic M. Neutrophil extracellular traps: double-edged swords of innate immunity // J Immunol. – 2012. – Vol. 189, № 6 – P. 2689-2695. https://doi.org/10.4049/jimmunol.1201719
36. Keshari R.S., Verma A., Barthwal M.K., Dikshit M. Reactive oxygen species-induced activation of ERK and p38 MAPK mediates PMA-induced NETs release from human neutrophils // J Cell Biochem. – 2012. – Vol. 114, № 3. – P. 532-540. https://doi.org/10.1002/jcb.24391
37. Kirchner T., Möller S., Klinger M., Solbach W., Laskay T., Behnen M. The impact of various reactive oxygen species on the formation of neutrophil extracellular traps // Mediators Inflamm. – 2012. – № 2012. – P. 849136. https://doi.org/10.1155/2012/849136
38. Li P., Li M., Lindberg M.R., Kennett M.J., Xiong N., Wang Y. PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps // J Exp Med. – 2010. – Vol. 207, № 9 – P. 1853-1862. https://doi.org/10.1084/jem.20100239
39. Martineau A.R., Newton S.M., Wilkinson K.A., Kampmann B., Hall B.M., Nawroly N., Packe G., Davidson R.N., Griffiths C.J., Wilkinson R.J. Neutrophil-mediated innate immune resistance to mycobacteria // J. Clin. Invest. – 2007. – Vol. 117, № 7 – P. 1988-1994. https://doi.org/10.1172/JCI31097
40. Mayadas T.N., Cullere X., Lowell C.A. The Multifaceted functions of neutrophils // Annu. Rev. Pathol. – 2014. – № 9. – P. 181-218. https://doi.org/10.1146/annurev-pathol-020712-164023
41. McCormick A., Heesemann L., Wagener J., Marcos V., Hartl D., Loeffler J., et al. NETs formed by human neutrophils inhibit growth of the pathogenic mold // Aspergillus fumigatus. Microbes Infect. – 2010. – Vol. 12, № 12-13. – P. 928-936. https://doi.org/10.1016/j.micinf.2010.06.009
42. Miralda I., Uriarte S.M., McLeish K.R. Multiple phenotypic changes define neutrophil priming // Front. Cell. Infect. Microbiol. – 2017. – № 7. – P. 217. https://doi.org/10.3389/fcimb.2017.00217
43. Nathan C., Cunningham-Bussel A. Beyond oxidative stress: an immunologist’s guide to reactive oxygen species // Nat. Rev. Immunol. – 2013. – Vol. 13, № 5. – P. 349-361. https://doi.org/10.1038/nri3423
44. Nathan C. Neutrophils and immunity: challenges and opportunities // Nat Rev Immunol. – 2006. – Vol. 6, № 3. – P. 173-182. https://doi.org/10.1038/nri1785
45. Nathan C. Points of control in inflammation // Nature. – 2002. – Vol. 420, № 6917. – P. 846-852. https://doi.org/10.1038/nature01320
46. N’Diaye E.-N., Darzacq X., Astarie-Dequeker C., Daffé M., Calafat J., Maridonneau-Parini I. Fusion of azurophil granules with phagosomes and activation of the tyrosine kinase hck are specifically inhibited during phagocytosis of mycobacteria by human neutrophils // J. Immunol. – 1998. – Vol. 161, № 9. – P. 4983-4991.
47. Ong C.W.M., Elkington P.T., Brilha S., Ugarte-Gil C., Tome-Esteban M.T., Tezera L.B., et al. Neutrophil-derived MMP-8 drives AMPK dependent matrix destruction in human pulmonary tuberculosis // PLoS Pathog. – 2015. – Vol. 11, № 5. – Р. e1004917. https://doi.org/10.1371/journal.ppat.1004917
48. Orme I.M. A new unifying theory of the pathogenesis of tuberculosis // Tuberculosis (Edinb). – 2014. – Vol. 94, № 1. – P. 8-14. https://doi.org/10.1016/j.tube.2013.07.004
49. Papayannopoulos V., Metzler K.D., Hakkim A., Zychlinsky A. Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps // J Cell Biol. – 2010. – Vol. 191, № 3. – P. 677-691. https://doi.org/10.1083/jcb.201006052
50. Papayannopoulos V. Neutrophil extracellular traps in immunity and disease // Nat Rev Immunol. – 2018. – Vol. 18. № 2. – P. 134-147.
51. Parker H., Dragunow M., Hampton M.B., Kettle A.J., Winterbourn C.C. Requirements for NADPH oxidase and myeloperoxidase in neutrophil extracellular trap formation differ depending on the stimulus // J Leukoc Biol. – 2012. – Vol. 92, № 4. – P. 841-849. https://doi.org/10.1189/jlb.1211601
52. Pilsczek F.H., Salina D., Poon K.K.H., Fahey C., Yipp B.G., Sibley C.D., et al. A novel mechanism of rapid nuclear neutrophil extracellular trap formation in response to Staphylococcus aureus // J. Immunol. – 2010. – Vol. 185, № 12. – P. 7413 -7425. https://doi.org/10.4049/jimmunol.1000675
53. Pleskova S.N., Gorshkova E.N., Kriukov R.N. Dynamics of formation and morphological features of neutrophil extracellular traps formed under the influence of opsonized Staphylococcus aureus // J. Mol. Recognition. – 2018. – Vol. 31, № 7. – Р. e2707.https://doi.org/10.1002/jur.2707
54. Ramos-Kichik V., Mondragón-Flores R., Mondragón-Castelán M., Gonzalez-Pozos S., Muñiz-Hernandez S., Rojas-Espinosa O., et al. Neutrophil extracellular traps are induced by Mycobacterium tuberculosis // Tuberculosis. – 2009. – Vol. 89, № 1. – P. 29-37. https://doi.org/10.1016/j.tube.2008.09.009
55. Rivas-Santiago B., Hernandez-Pando R., Carranza C., Juarez E., Contreras J.L., Aguilar-Leon D., Torres M., Sada E. Expression of cathelicidin LL-37 during Mycobacterium tuberculosis infection in human alveolar macrophages, monocytes, neutrophils, and epithelial cells // Infect. Immun. – 2008. – Vol. 76, № 3. – P. 935–941. https://doi.org/10.1128/IAI.01218-07
56. Saitoh T., Komano J., Saitoh Y., Misawa T., Takahama M., Kozaki T., et al. Neutrophil extracellular traps mediate a host defense response to human immunodeficiency virus-1 // Cell Host Microbe. – 2012. – Vol. 12, № 1. – P. 109-116. https://doi.org/10.1016/j.chom.2012.05.015
57. Segal A.W. How neutrophils kill microbes // Annu Rev Immunol. – 2005. – № 23. – P. 197-223. https://doi.org/10.1146/annurev.immunol.23.021704.115653
58. Sharma S., Verma I., Khuller G.K. Therapeutic potential of human neutrophil peptide 1 against experimental tuberculosis // Antimicrob. Agents Chemother. – 2001. – Vol. 45, № 2. – P. 639-640. https://doi.org/10.1128/AAC.45.2.639-640.2001
59. Siebert J.N., Hamann L., Verolet C.M., Gameiro C., Grillet S., Siegrist C.A., Posfay-Barbe K.M. Toll-interleukin 1 receptor domain-containing adaptor protein 180L singlenucleotide polymorphism is associated with susceptibility to recurrent pneumococcal lower respiratory tract infections in children // Front Immunol. – 2018. – № 9. – P. 1780. https://doi.org/10.3389/fimmu.2018.01780
60. Skendros P., Mitroulis I., Ritis K. Autophagy in Neutrophils: From Granulopoiesis to Neutrophil Extracellular Traps // Front Cell Dev Biol. – 2018. – № 6. – P. 109. https://doi.org/10.3389fcell.2018.00109
61. Sousa-Rocha D., Thomaz-Tobias M., Diniz L.F., Souza P.S., Pinge-Filho P., Toledo K.A. Trypanosoma cruzi and its soluble antigens induce NET release by stimulating tolllike receptors // PLoS One. – 2015. – Vol. 10, № 10. – Р. e0139569. https://doi.org/10.1371/journal.pone.0139569
62. Stakos D.A., Kambas K., Konstantinidis T. et al. Immunomodulatory Role of Clarithromycin in Acinetobacter baumanii Infection via Formation of Neutrophil Extracellular Traps // Antimicrob Agents Chemother. – 2015. – Vol. 60, № 2. – P. 1040-1048.
63. Urban C.F., Ermert D., Schmid M., Abu-Abed U., Goosmann C., Nacken W., et al. Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans // PLoS Pathog. – 2009. – Vol. 5, № 10. – Р. e1000639. https://doi.org/10.1371/journal.ppat.1000639
64. Voskuil M.I., Bartek I.L., Visconti K., Schoolnik G.K. The response of Mycobacterium tuberculosis to reactive oxygen and nitrogen species // Front. Microbiol. – 2011. – № 2. – P. 105. https://doi.org/10.3389/fmicb.2011.00105
65. Warnatsch A., Tsourouktsoglou T.D., Branzk N., Wang Q., Reincke S., Herbst S., Gutierrez M., Papayannopoulos V. Reactive oxygen species localization programs inflammation to clear microbes of different size // Immunity. – 2017. – Vol. 46, № 3. – P. 421-432. https://doi.org/10.1016/j.immuni.2017.02.013
66. World Health Organization // Global tuberculosis report. – Geneva: World Health Organization. – WHO, 2023. – Available at: https://www.who.int/publications/i/item/9789240083851 [Аccessed: 15.02.2023].
67. Yang H., Biermann M.H., Brauner J.M., et al. New insights into neutrophil extracellular traps: mechanisms of formation and role in inflammation // Front Immunol. – 2016. – № 7. – P. 302. https://doi.org/10.3389/fimmu.2016.00302
68. Yousefi S., Simon H.U. NETosis - Does It Really Represent Nature’s “Suicide Bomber”? // Front Immunol. – 2016. – № 7. – P. 328. https://doi.org/10.3389/fimmu.2016.00328
69. Zanetti M. Cathelicidins, multifunctional peptides of the innate immunity // J. Leukoc. Biol. – 2004. – Vol. 75, № 1. – P. 39-48. https://doi.org/10.1189/jlb.0403147
Рецензия
Для цитирования:
Мордык А.В., Иванова О.Г., Золотов А.Н., Романова М.А., Птухин А.О., Новиков Д.Г. Нейтрофильные внеклеточные ловушки и туберкулез: патогенетическая роль и особенности формирования. Туберкулез и болезни легких. 2025;103(5):102-111. https://doi.org/10.58838/2075-1230-2025-103-5-102-111
For citation:
Mordyk A.V., Ivanova O.G., Zolotov A.N., Romanova M.A., Ptukhin A.O., Novikov D.G. Neutrophil Extracellular Traps and Tuberculosis: Pathogenetic Role and Formation Patterns. Tuberculosis and Lung Diseases. 2025;103(5):102-111. (In Russ.) https://doi.org/10.58838/2075-1230-2025-103-5-102-111




































