Neutrophil Extracellular Traps and Tuberculosis: Pathogenetic Role and Formation Patterns

The review analyzes 69 publications discussing formation mechanisms of neutrophil extracellular traps in various infectious and non-infectious diseases. It depicts patterns of formation of neutrophil extracellular traps in active respiratory tuberculosis and their role in the pathogenesis of disseminated destructive forms of the disease. It provides information on age-related characteristics of the neutrophil net-forming function in tuberculosis infection.

1. Vorobyeva N.V., Chernyak B.V. NETosis: molecular mechanisms, role in physiology and pathology. Biokhimiya, 2020, vol. 85, no. 10, pp. 1383-1397. (In Russ.)

2. Iliadi V.A., Iliadis S.A., Konstantinidis T.G. Neutrophil extracellular traps. Modern Science, 2020, no. 12, pp. 95-99. (In Russ.)

3. Karnaushkina M.A., Guryev A.S., Mironov K.O., Dunaeva E.A., Korchagin V.I., Bobkova O.Yu., Vasilyeva I.S., Kassina D.V., Litvinova M.M. Associations of toll-like receptor gene polymorphisms with NETosis activity as prognostic criteria for the severity of pneumonia. Sovremennye Tekhnologii v Meditsine, 2021, vol. 13, no. 3, pp. 47-54. (In Russ.) https://doi.org/10.17691/stm2021.13.3.06

4. Linge I.A., Apt A.S. A controversial role of neutrophils in tuberculosis infection pathogenesis. Russian Journal of Infection and Immunity, 2021, vol. 11, no. 5, pp. 809-819. (In Russ.) https://doi.org/10.15789/2220-7619-ACR-1670

5. Lotosh N.Yu., Alyaseva S.O., Vasilov R.G., Selischeva A.A. Sterilamine induces the formation of neutrophil extracellular traps independently of reactive oxygen species. Tsitologiya, 2019, vol. 61, no. 4, pp. 308-318. (In Russ.) https://doi.org/10.1134.S0041377119040035

6. Mordyk A.V., Zolotov A.N., Novikov D.G. et al. Age-related differences of forming neutrophil extracellular traps in healthy individuals and in tuberculosis patients. Vestnik Sovremennoy Klinicheskoy Meditsiny, 2023, vol. 16, no. 6, pp. 37-45. (In Russ.) https://doi.org/10.20969/VSKM.2023.16(6).37-45.

7. Mordyk A.V., Zolotov A.N., Novikov D.G., Kirichenko N.A., Pakhtusova P.O., Ptukhin A.O. NETosis-forming ability of neutrophils in patients with limited and disseminated tuberculous lesions. Tuberculosis and Lung Diseases, 2023, vol. 101, no. 3, pp. 78-86. (In Russ.) https://doi.org/10.58838/2075-1230-2023-101-3-78-86

8. Pleskova S.N., Gorshkova E.N., Boryakov A.V., Kryukov R.N. Morphological features of fast and classical netosis. Tsitologiya, 2019, vol. 61, no. 9, pp. 704-712. (In Russ.)

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, no. 1, pp. 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, no. 5663, pp. 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, no. 8, pp. 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, no. 5, pp. 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, no. 8, pp. 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, no. 46, pp. 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, no. 4, pp. 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, no. 1, pp. 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, no. 7, pp. 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, no. 6, pp. 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, no. 6, pp. 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, no. 3, pp. 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, no. 4, pp. 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, no. 9, pp. 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, no. 5, pp. 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, no. 1, pp. 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, no. 10, pp. 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, no. 2, pp. 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, no. 4, pp. 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, no. 9, pp. 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, no. 16, pp. 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, no. 10, pp. 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, no. 8, pp. 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, no. 12, pp. 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, no. 2, pp. 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, no. 3, pp. 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, no. 6, pp. 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, no. 3, pp. 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, no. 2012, pp. 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, no. 9, pp. 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, no. 7, pp. 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, no. 9, pp. 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, no. 12-13, pp. 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, no. 7, pp. 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, no. 5, pp. 349-361. https://doi.org/10.1038/nri3423

44. Nathan C. Neutrophils and immunity: challenges and opportunities. Nat. Rev. Immunol., 2006, vol. 6, no. 3, pp. 173-182. https://doi.org/10.1038/nri1785

45. Nathan C. Points of control in inflammation. Nature, 2002, vol. 420, no. 6917, pp. 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, no. 9, pp. 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, no. 5, pp. 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, no. 1, pp. 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, no. 3, pp. 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, no. 2, pp. 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, no. 4, pp. 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, no. 12, pp. 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, no. 7, pp. 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, no. 1, pp. 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, no. 3, pp. 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, no. 1, pp. 109-116. https://doi.org/10.1016/j.chom.2012.05.015

57. Segal A.W. How neutrophils kill microbes. Annu. Rev. Immunol., 2005, no. 23, pp. 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, no. 2, pp. 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, no. 9, pp. 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, no. 6, pp. 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, no. 10, pp. 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, no. 2, pp. 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, no. 10, pp. 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, no. 2, pp. 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, no. 3, pp. 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: https://www.who.int/publications/i/item/9789240083851 Аccessed February 15, 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, no. 7, pp. 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, no. 7, pp. 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, no. 1, pp. 39-48. https://doi.org/10.1189/jlb.0403147