A controversial role of neutrophils in tuberculosis infection pathogenesis

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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.

About the authors

I. A. Linge

Central Tuberculosis Research Institute

Author for correspondence.
Email: iralinge@gmail.com
ORCID iD: 0000-0003-1535-5800

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

107564, Moscow, Yauzskaya alley, 2

Phone: +7 499 785-90-72 

Russian Federation

A. S. Apt

Central Tuberculosis Research Institute

Email: alexapt0151@gmail.com
ORCID iD: 0000-0002-3683-3085

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


Russian Federation


  1. Abadie V., Badell E., Douillard P., Ensergueix D., Leenen P.J.M., Tanguy M., Fiette L., Saeland S., Gicquel B., Winter N. Neutrophils rapidly migrate via lymphatics after Mycobacterium bovis BCG intradermal vaccination and shuttle live bacilli to the draining lymph nodes. Blood, 2005, vol. 106, pp. 1843–1850. doi: 10.1182/blood-2005-03-1281
  2. Bazzoni F., Cassatella M.A., Rossi F., Ceska M., Dewald B., Baggiolini M. Phagocytosing neutrophils produce and release high amounts of the neutrophil-activating peptide 1/interleukin 8. J. Exp. Med., 1991, vol. 173, pp. 771–774. doi: 10.1084/jem.173.3.771
  3. Berry M.P.R., Graham C.M., McNab F.W., Xu Z., Bloch S.A.A., Oni T., Wilkinson K.A., Banchereau R., Skinner J., Wilkinson R.J., Quinn C., Blankenship D., Dhawan R., Cush J.J., Mejias A., Ramilo O., Kon O.M., Pascual V., Banchereau J., Chaussabel D., O’Garra A. An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis. Nature, 2010, vol. 466, pp. 973–977. doi: 10.1038/nature09247
  4. Blomgran R., Desvignes L., Briken V., Ernst J.D. Mycobacterium tuberculosis inhibits neutrophil apoptosis, leading to delayed activation of naive CD4 T cells. Cell Host Microbe, 2012, vol. 11, pp. 81–90. doi: 10.1016/j.chom.2011.11.012
  5. Blomgran R., Ernst J.D. Lung neutrophils facilitate activation of naive antigen-specific CD4+ T cells during Mycobacterium tuberculosis infection. J. Immunol., 2011, vol. 186, pp. 7110–7119. doi: 10.4049/jimmunol.1100001
  6. Bober L.A., Grace M.J., Pugliese-Sivo C., Rojas-Triana A., Waters T., Sullivan L.M., Narula S.K. The effect of GM-CSF and G-CSF on human neutrophil function. Immunopharmacology, 1995, vol. 29, pp. 111–119. doi: 10.1016/0162-3109(94)00050-P
  7. Braian C., Hogea V., Stendahl O. Mycobacterium tuberculosis-induced neutrophil extracellular traps activate human macrophages. J. Innate Immun., 2013, vol. 5, pp. 591–602. doi: 10.1159/000348676
  8. Brinkmann V., Reichard U., Goosmann C., Fauler B., Uhlemann Y., Weiss D.S., Weinrauch Y., Zychlinsky A. Neutrophil extracellular traps kill bacteria. Science, 2004, vol. 303, pp. 1532–1535. doi: 10.1126/science.1092385
  9. 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. doi: 10.1073/pnas.1210500109
  10. Choi H., Chon H.R., Kim K., Kim S., Oh K.J., Jeong S.H., Jung W.J., Shin B., Jhun B.W., Lee H., Park H.Y., Koh W.J. Clinical and laboratory differences between lymphocyte- and neutrophil-predominant pleural tuberculosis. PLoS One, 2016, vol. 11, no. 10: e0165428. doi: 10.1371/journal.pone.0165428
  11. Choreño-Parra J.A., Bobba S., Rangel-Moreno J., Ahmed M., Mehra S., Rosa B., Martin J., Mitreva M., Kaushal D., Zúñiga J., Khader S.A. Mycobacterium tuberculosis HN878 infection induces human-like B-cell follicles in mice. J. Infect. Dis., 2020, vol. 221, pp. 1636–1646. doi: 10.1093/infdis/jiz663
  12. Cohen S.B., Gern B.H., Delahaye J.L., Adams K.N., Plumlee C.R., Winkler J.K., Sherman D.R., Gerner M.Y., Urdahl K.B. Alveolar macrophages provide an early Mycobacterium tuberculosis niche and initiate dissemination. Cell Host Microbe, 2018, vol. 24, pp. 439–446. doi: 10.1016/j.chom.2018.08.001
  13. Condliffe A.M., Chilvers E.R., Haslett C., Dransfield I. Priming differentially regulates neutrophil adhesion molecule expression/function. Immunology, 1996, vol. 89, pp. 105–111. doi: 10.1046/j.1365-2567.1996.d01-711.x
  14. 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, pp. 1109–1121. doi: 10.1111/j.1462-5822.2012.01783.x
  15. 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, pp. 519.e3–530.e3. doi: 10.1016/j.chom.2017.09.003
  16. 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, pp. 533–538. doi: 10.1111/j.1365-2249.1993.tb08230.x
  17. Das R., Koo M.S., Kim B.H., Jacob S.T., Subbian S., Yao J., Leng L., Levy R., Murchison C., Burman W.J., Moore C.C., Michael Scheld W., David J.R., Kaplan G., MacMicking J.D., Bucala R. Macrophage migration inhibitory factor (MIF) is a critical mediator of the innate immune response to Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA, 2013, vol. 110: E2997. doi: 10.1073/pnas.1301128110
  18. Deffert C., Cachat J., Krause K.H. Phagocyte NADPH oxidase, chronic granulomatous disease and mycobacterial infections. Cell Microbiol., 2014, vol. 16, pp. 1168–1178. doi: 10.1111/cmi.12322
  19. DeLeo F.R. Modulation of phagocyte apoptosis by bacterial pathogens. Apoptosis, 2004, vol. 9, pp. 399–413. doi: 10.1023/B:APP T.0000031448.64969.fa
  20. Desvignes L., Ernst J.D. Interferon-γ-responsive nonhematopoietic cells regulate the immune response to Mycobacterium tuberculosis. Immunity, 2009, vol. 31, pp. 974–985. doi: 10.1016/j.immuni.2009.10.007
  21. Dorhoi A., Desel C., Yeremeev V., Pradl L., Brinkmann V., Mollenkopf H.J., Hanke K., Gross O., Ruland J., Kaufmann S.H.E. The adaptor molecule CARD9 is essential for tuberculosis control. J. Exp. Med., 2010, vol. 207, pp. 777–792. doi: 10.1084/jem.20090067
  22. Dorhoi A., Iannaccone M., Farinacci M., Faé K.C., Schreiber J., Moura-Alves P., Nouailles G., Mollenkopf H.J., OberbeckMüller D., Jörg S., Heinemann E., Hahnke K., Löwe D., Del Nonno F., Goletti D., Capparelli R., Kaufmann S.H.E. MicroRNA-223 controls susceptibility to tuberculosis by regulating lung neutrophil recruitment. J. Clin. Invest., 2013, vol. 123, pp. 4836–4848. doi: 10.1172/JCI67604
  23. Ellison M.A., Gearheart C.M., Porter C.C., Ambruso D.R. IFN-γ alters the expression of diverse immunity related genes in a cell culture model designed to represent maturing neutrophils. PLoS One, 2017, vol. 12: e0185956. doi: 10.1371/journal.pone.0185956
  24. Eruslanov E.B., Lyadova I.V., Kondratieva T.H., Majorov K.B., Scheglov I.V., Orlova M.O., Apt A.S. Neutrophil responses to Mycobacterium tuberculosis infection in genetically susceptible and resistant mice neutrophil responses to Mycobacterium tuberculosis infection in genetically susceptible and resistant mice. Infect. Immun., 2005, vol. 73, pp. 1744–1753. doi: 10.1128/IAI.73.3.1744
  25. Ethuin F., Gérard B., Benna J.E., Boutten A., Gougereot-Pocidalo M.A., Jacob L., Chollet-Martin S. Human neutrophils produce interferon gamma upon stimulation by interleukin-12. Lab. Investig., 2004, vol. 84, pp. 1363–1371. doi: 10.1038/labinvest.3700148
  26. Eum S.Y., Kong J.H., Hong M.S., Lee Y.J., Kim J.H., Hwang S.H., Cho S.H., Via S.N., Laura E., Clifton B.E. Neutrophils are the predominant infected phagocytic cells in the airways of patients with active pulmonary TB. Chest, 2010, vol. 137, pp. 122–128. doi: 10.1378/chest.09-0903
  27. 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: e1474. doi: 10.1038/cddis.2014.394
  28. Futosi K., Fodor S., Mócsai A. Reprint of neutrophil cell surface receptors and their intracellular signal transduction pathways. Int. Immunopharmacology, 2013, vol. 17, pp. 1185–1197. doi: 10.1016/j.intimp.2013.11.010
  29. Ganz T. Defensins: Antimicrobial peptides of innate immunity. Nat. Rev. Immunol., 2003, vol. 3, pp. 710–720. doi: 10.1038/nri1180
  30. Gopal R., Monin L., Torres D., Slight S., Mehra S., McKenna K.C., Junecko B.A.F., Reinhart T.A., Kolls J., Báez-Saldańa R., Cruz-Lagunas A., Rodríguez-Reyna T.S., Kumar N.P., Tessier P., Roth J., Selman M., Becerril-Villanueva E., BaqueraHeredia J., Cumming B., Kasprowicz V.O., Steyn A.J.C., Babu S., Kaushal D., Zúñiga J., Vogl T., Rangel-Moreno J., Khader Sh.A. S100A8/A9 proteins mediate neutrophilic inflammation and lung pathology during tuberculosis. Am. J. Respir. Crit. Care Med., 2013, vol. 188, pp. 1137–1146. doi: 10.1164/rccm.201304-0803OC
  31. Alvarez-Jiménez V.D., Leyva-Paredes K., Campillo-Navarro M., Romo-Cruz I., Hugo Rosales-García V., CastañedaCasimiro J., González-Pozos S., Manuel Hernández J., Wong-Baeza C., Estela García-Pérez B., Ortiz-Navarrete V., EstradaParra S., Serafín-López J., Wong-Baeza I., Estrada-García I. Extracellular vesicles released from Mycobacterium tuberculosisinfected neutrophils promote macrophage autophagy and decrease intracellular mycobacterial survival. Front. Immunol., 2018, vol. 9: 272. doi: 10.3389/fimmu.2018.00272
  32. Hilda J.N., Das S., Tripathy S.P., Hanna L.E. Role of neutrophils in tuberculosis: a bird’s eye view. Innate Immun., 2020, vol. 26, no. 4, pp. 240–247. doi: 10.1177/1753425919881176
  33. 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: e50345. doi: 10.1371/journal.pone.0050345
  34. Jin L., Batra S., Douda D.N., Palaniyar N., Jeyaseelan S. CXCL1 contributes to host defense in polymicrobial sepsis via modulating T cell and neutrophil functions. J. Immunol., 2014, vol. 193, pp. 3549–3558. doi: 10.4049/jimmunol.1401138
  35. Keller C., Hoffmann R., Lang R., Brandau S., Hermann C., Ehlers S. Genetically determined susceptibility to tuberculosis in mice causally involves accelerated and enhanced recruitment of granulocytes. Infect. Immun., 2006, vol. 74, pp. 4295–4309. doi: 10.1128/IAI.00057-06
  36. Kimmey J.M., Huynh J.P., Weiss L.A., Park S., Kambal A., Debnath J., Virgin H.W., Stallings C.L. Unique role for ATG5 in neutrophil-mediated immunopathology during M. tuberculosis infection. Nature, 2015, vol. 528, pp. 565–569. doi: 10.1038/nature16451
  37. Kondratieva T.K., Rubakova E.I., Linge I.A., Evstifeev V.V., Majorov K.B., Apt A.S. B cells delay neutrophil migration toward the site of stimulus: tardiness critical for effective Bacillus Calmette–Guerin vaccination against tuberculosis infection in mice. J. Immunol., 2010, vol. 184, pp. 1227–1234. doi: 10.4049/jimmunol.0902011
  38. Kroon E.E., Coussens A.K., Kinnear C., Orlova M., Möller M., Seeger A., Wilkinson R.J., Hoal E.G., Schurr E. Neutrophils: innate effectors of TB resistance? Front. Immunol., 2018, vol. 9: 2637. doi: 10.3389/fimmu.2018.02637
  39. Law K., Weiden M., Harkin T., Tchou-Wong K., Chi C., Rom W.N. Increased release of interleukin-1β, interleukin-6, and tumor necrosis factor-α by bronchoalveolar cells lavaged from involved sites in pulmonary tuberculosis. Am. J. Respir. Crit. Care Med., 1996, vol. 153, pp. 799–804. doi: 10.1164/ajrccm.153.2.8564135
  40. Liles W.C., Ledbetter J.A., Waltersdorph A.W., Klebanoff S.J. Cross-linking of CD18 primes human neutrophils for activation of the respiratory burst in response to specific stimuli: Implications for adhesion-dependent physiological responses in neutrophils. J. Leukoc. Biol., 1995, vol. 58, pp. 690–697. doi: 10.1002/jlb.58.6.690
  41. Lovewell R.R., Baer C.E., Mishra B.B., Smith C.M., Sassetti C.M. Granulocytes act as a niche for Mycobacterium tuberculosis growth. Mucosal Immunol., 2020, vol. 14, pp. 229–241. doi: 10.1038/s41385-020-0300-z
  42. Lowe D.M., Bandara A.K., Packe G.E., Barker R.D., Wilkinson R.J., Griffiths C.J., Martineau A.R. Neutrophilia independently predicts death in tuberculosis. Eur. Respir. J., 2013, vol. 42, pp. 1752–1757. doi: 10.1183/09031936.00140913
  43. Lowe D.M., Demaret J., Bangani N., Nakiwala J.K., Goliath R., Wilkinson K.A., Wilkinson R.J., Martineau A.R. Differential effect of viable versus necrotic neutrophils on mycobacterium tuberculosis growth and cytokine induction in whole blood. Front. Immunol., 2018, vol. 9: 27. doi: 10.3389/fimmu.2018.00903
  44. Lyadova I.V. Review article neutrophils in tuberculosis: heterogeneity shapes the way? Mediators Inflamm., 2017, vol. 2017: 8619307. doi: 10.1155/2017/8619307
  45. 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, pp. 1988–1994. doi: 10.1172/JCI31097
  46. Marzo E., Vilaplana C., Tapia G., Diaz J., Garcia V., Cardona P.-J. Damaging role of neutrophilic infiltration in a mouse model of progressive tuberculosis. Tuberculosis, 2014, vol. 94, pp. 55–64. doi: 10.1016/j.tube.2013.09.004
  47. Mayadas T.N., Cullere X., Lowell C.A. The Multifaceted functions of neutrophils. Annu. Rev. Pathol., 2014, vol. 9, pp. 181–218. doi: 10.1146/annurev-pathol-020712-164023
  48. McCracken J.M., Allen L.A.H. Regulation of human neutrophil apoptosis and lifespan in health and disease. J. Cell Death, 2014, vol. 7, pp. 15–23. doi: 10.4137/JCD.S11038
  49. Miralda I., Uriarte S.M., McLeish K.R. Multiple phenotypic changes define neutrophil priming. Front. Cell. Infect. Microbiol., 2017, vol. 7: 217. doi: 10.3389/fcimb.2017.00217
  50. Mitra S., Abraham E. Participation of superoxide in neutrophil activation and cytokine production. Biochim. Biophys. Acta-Mol. Basis. Dis., 2006, vol. 1762, pp. 732–741. doi: 10.1016/j.bbadis.2006.06.011
  51. Muefong C.N., Sutherland J.S. Neutrophils in tuberculosis-associated inflammation and lung pathology. Front. Immunol., 2020, vol. 11: 962. doi: 10.3389/fimmu.2020.00962
  52. 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, pp. 4983–4991.
  53. Nandi B., Behar S.M. Regulation of neutrophils by interferon-γ limits lung inflammation during tuberculosis infection. J. Exp. Med., 2011, vol. 208, pp. 2251–2262. doi: 10.1084/jem.20110919
  54. Nathan C. Points of control in inflammation. Nature, 2002, vol. 420, pp. 846–852. doi: 10.1038/nature01320
  55. Nathan C., Cunningham-Bussel A. Beyond oxidative stress: an immunologist’s guide to reactive oxygen species. Nat. Rev. Immunol., 2013, vol. 13, pp. 349–361. doi: 10.1038/nri3423
  56. Neufert C., Pai R.K., Noss E.H., Berger M., Boom W.H., Harding C.V. Mycobacterium tuberculosis 19-kDa lipoprotein promotes neutrophil activation. J. Immunol., 2001, vol. 167, pp. 1542–1549. doi: 10.4049/jimmunol.167.3.1542
  57. Niazi M.K.K., Dhulekar N., Schmidt D., Major S., Cooper R., Abeijon C., Gatti D.M., Kramnik I., Yener B., Gurcan M., Beamer G. Lung necrosis and neutrophils reflect common pathways of susceptibility to Mycobacterium tuberculosis in genetically diverse, immune-competent mice. Dis. Model. Mech., 2015, vol. 8, pp. 1141–1153. doi: 10.1242/dmm.020867
  58. Nouailles G., Dorhoi A., Koch M., Zerrahn J., Weiner J., Faé K.C., Arrey F., Kuhlmann S., Bandermann S., Loewe D., Mollen kopf H.J., Vogelzang A., Meyer-Schwesinger C., Mittrücker H.W., McEwen G., Kaufmann S.H.E. CXCL5-secreting pulmonary epithelial cells drive destructive neutrophilic inflammation in tuberculosis. J. Clin. Invest., 2014, vol. 124, pp. 1268–1282. doi: 10.1172/JCI72030
  59. O’Garra A., Redford P.S., McNab F.W., Bloom C.I., Wilkinson R.J., Berry M.P.R. The immune response in tuberculosis. Annu. Rev. Immunol., 2013, vol. 31, pp. 475–527. doi: 10.1146/annurev-immunol-032712-095939
  60. Papayannopoulos V., Zychlinsky A. NETs: a new strategy for using old weapons. Trends Immunol., 2009, vol. 30, pp. 513–521. doi: 10.1016/j.it.2009.07.011
  61. Petrofsky M., Bermudez L.E. Neutrophils from Mycobacterium avium-infected mice produce TNFα, IL-12, and IL-1β and have a putative role in early host response. Clin. Immunol., 1999, vol. 91, pp. 354–358. doi: 10.1006/clim.1999.4709
  62. Riedel D.D., Kaufmann S.H.E. Chemokine secretion by human polymorphonuclear granulocytes after stimulation with mycobacterium tuberculosis and lipoarabinomannan. Infect. Immun., 1997, vol. 65, pp. 4620–4623. doi: 10.1128/IAI.65.11.4620-4623.1997
  63. 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, pp. 935–941. doi: 10.1128/IAI.01218-07
  64. Russell D.G. Mycobacterium tuberculosis: here today, and here tomorrow. Nat. Rev. Mol. Cell Biol., 2001, vol. 2, pp. 569–577. doi: 10.1038/35085034
  65. Russell D.G. Who puts the tubercle in tuberculosis? Nat. Rev. Microbiol., 2007, vol. 5, pp. 39–47. doi: 10.1038/nrmicro1538
  66. Ryckman C., McColl S.R., Vandal K., De Médicis R., Lussier A., Poubelle P.E., Tessier P.A. Role of S100A8 and S100A9 in neutrophil recruitment in response to monosodium urate monohydrate crystals in the air-pouch model of acute gouty arthritis. Arthritis Rheum., 2003, vol. 48, pp. 2310–2320. doi: 10.1002/art.11079
  67. Sakai S., Kauffman K.D., Sallin M.A., Sharpe A.H., Young H.A., Ganusov V.V., Barber V.V., Daniel L. CD4 T cell-derived IFN-γ plays a minimal role in control of pulmonary Mycobacterium tuberculosis infection and must be actively repressed by PD-1 to prevent lethal disease. PLoS Pathog., 2016, vol. 12, no. 5: e1005667. doi: 10.1371/journal.ppat.1005667
  68. Sawant K.V., McMurray D.N. Guinea pig neutrophils infected with Mycobacterium tuberculosis produce cytokines which activate alveolar macrophages in noncontact cultures. Infect. Immun., 2007, vol. 75, pp. 1870–1877. doi: 10.1128/IAI.00858-06
  69. Schneider B.E., Korbel D., Hagens K., Koch M., Raupach B., Enders J., Kaufmann S.H.E., Mittrücker H.W., Schaible U.E. A role for IL-18 in protective immunity against Mycobacterium tuberculosis. Eur. J. Immunol., 2010, vol. 40, pp. 396–405. doi: 10.1002/eji.200939583
  70. Scott N.R., Swanson R.V., Al-Hammadi N., Domingo-Gonzalez R., Rangel-Moreno J., Kriel B.A., Domingo-Gonzalez R., Rangel-Moreno J., Kriel B.A., Bucsan A.N., Das S., Ahmed M., Mehra S., Treerat P., Cruz-Lagunas A., Jimenez-Alvarez L., Muñoz-Torrico M., Bobadilla-Lozoya K., Vogl T., Walzl G., du Plessis N., Kaushal D., Scriba T., Zuñiga J., Khader S. S100A8/ A9 regulates CD11b expression and neutrophil recruitment during chronic tuberculosis. J. Clin. Invest., 2020, vol. 130, no. 6, pp. 3098–3112. doi: 10.1172/JCI130546
  71. Seiler P., Aichele P., Raupach B., Odermatt B., Steinhoff U., Kaufmann S.H.E. Rapid neutrophil response controls fast-replicating intracellular bacteria but not slow-replicating Mycobacterium tuberculosis. J. Infect. Dis., 2000, vol. 181, pp. 671–680. doi: 10.1086/315278
  72. Sharma S., Verma I., Khuller G.K. Therapeutic potential of human neutrophil peptide 1 against experimental tuberculosis. Antimicrob. Agents Chemother., 2001, vol. 45, pp. 639–640. doi: 10.1128/AAC.45.2.639-640.2001
  73. Shea-Donohue T., Thomas K., Cody M.J., Zhao A., Detolla L.J., Kopydlowski K.M., Fukata M., Lira S.A., Vogel S.N. Mice deficient in the CXCR2 ligand, CXCL1 (KC/GRO-α), exhibit increased susceptibility to dextran sodium sulfate (DSS)-induced colitis. Innate Immun., 2008, vol. 14, pp. 117–124. doi: 10.1177/1753425908088724
  74. Spiekermann K., Roesler J., Emmendoerffer A., Elsner J., Welte K. Functional features of neutrophils induced by G-CSF and GMCSF treatment: Differential effects and clinical implications. Leukemia, 1997, vol. 11, pp. 466–478. doi: 10.1038/sj.leu.2400607
  75. Stamm C.E., Collins A.C., Shiloh M.U. Sensing of Mycobacterium tuberculosis and consequences to both host and bacillus. Immunol. Rev., 2015, vol. 264, pp. 204–219. doi: 10.1111/imr.12263
  76. Steinwede K., Maus R., Bohling J., Voedisch S., Braun A., Ochs M., Schmiedl A., Länger F., Gauthier F., Roes J., Welte T., Bange F.C., Niederweis M., Bühling F., Maus U.A. Cathepsin G and neutrophil elastase contribute to lung-protective immunity against mycobacterial infections in mice. J. Immunol., 2012, vol. 188, pp. 4476–4487. doi: 10.4049/jimmunol.1103346
  77. Stek C., Allwood B., Walker N.F., Wilkinson R.J., Lynen L., Meintjes G. The immune mechanisms of lung parenchymal damage in tuberculosis and the role of host-directed therapy. Front. Microbiol., 2018, vol. 9: 2603. doi: 10.3389/fmicb.2018.02603
  78. Strieter R.M., Kasahara K., Allen R.M., Standiford T.J., Rolfe M.W., Becker F.S., Chensue S.W., Kunkel S.L. Cytokine-induced neutrophil-derived interleukin-8. Am. J. Pathol., 1992, vol. 141, pp. 397–407. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1886610
  79. Sugawara I., Udagawa T., Yamada H. Rat neutrophils prevent the development of tuberculosis. Infect. Immun., 2004, vol. 72, pp. 1804–1806. doi: 10.1128/IAI.72.3.1804-1806.2004
  80. Summers C., Rankin S.M., Condliffe A.M., Singh N., Peters A.M., Chilvers E.R. Neutrophil kinetics in health and disease. Trends Immunol., 2010, vol. 31, pp. 318–324. doi: 10.1016/j.it.2010.05.006
  81. Sunahori K., Yamamura M., Yamana J., Takasugi K., Kawashima M., Yamamoto H., Chazin W.J., Nakatani Y., Yui S., Makino H. The S100A8/A9 heterodimer amplifies proinflammatory cytokine production by macrophages via activation of nuclear factor kappa B and p38 mitogen-activated protein kinase in rheumatoid arthritis. Arthritis Res. Ther., 2006, vol. 8: 69. doi: 10.1186/ar1939
  82. Sutherland J.S., Jeffries D.J., Donkor S., Walther B., Hill P.C., Adetifa I.M.O., Adegbola I.M.O., Ota R.A., Martin O.C. High granulocyte/lymphocyte ratio and paucity of NKT cells defines TB disease in a TB-endemic setting. Tuberculosis, 2009, vol. 89, pp. 398–404. doi: 10.1016/j.tube.2009.07.004
  83. Tan B.H., Meinken C., Bastian M., Bruns H., Legaspi A., Ochoa M.T., Krutzik S.R., Bloom B.R., Ganz T., Modlin R.L., Stenger S. Macrophages acquire neutrophil granules for antimicrobial activity against intracellular pathogens. J. Immunol., 2006, vol. 177, pp. 1864–1871. doi: 10.4049/jimmunol.177.3.1864
  84. Trentini M.M., de Oliveira F.M., Kipnis A., Junqueira-Kipnis A.P. The role of neutrophils in the induction of specific Th1 and Th17 during vaccination against tuberculosis. Front. Microbiol., 2016, vol. 7: 898. doi: 10.3389/fmicb.2016.00898
  85. Ueda Y., Cain D.W., Kuraoka M., Kondo M., Kelsoe G. IL-1R type I-dependent hemopoietic stem cell proliferation is necessary for inflammatory granulopoiesis and reactive neutrophilia. J. Immunol., 2009, vol. 182, pp. 6477–6484. doi: 10.4049/jimmunol.0803961
  86. Velmurugan K., Chen B., Miller J.L., Azogue S., Gurses S., Hsu T., Glickman M., Jacobs W.R., Porcelli S.A., Briken V. Mycobacterium tuberculosis nuoG is a virulence gene that inhibits apoptosis of infected host cells. PLoS Pathog., 2007, vol. 3, no. 7: e110. doi: 10.1371/journal.ppat.0030110
  87. 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, vol. 2: 105. doi: 10.3389/fmicb.2011.00105
  88. Vyas S.P., Goswami R. Striking the right immunological balance prevents progression of tuberculosis. Inflamm. Res., 2017, vol. 66, pp. 1031–1056. doi: 10.1007/s00011-017-1081-z
  89. 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, pp. 421–432. doi: 10.1016/j.immuni.2017.02.013
  90. Weisbart R.H., Golde D.W., Clark S.C., Wong G.G., Gasson J.C. Human granulocyte-macrophage colony-stimulating factor is a neutrophil activator. Nature, 1985, vol. 314, pp. 361–363. doi: 10.1038/314361a0
  91. Wengner A.M., Pitchford S.C., Furze R.C., Rankin S.M. The coordinated action of G-CSF and ELR CXC chemokines in neutrophil mobilization during acute inflammation. Blood, 2008, vol. 111, no. 1, pp. 42–49. doi: 10.1182/blood-2007-07-099648
  92. Witko-Sarsat V., Rieu P., Descamps-Latscha B., Lesavre P., Halbwachs-Mecarelli L. Neutrophils: molecules, functions and pathophysiological aspects. Lab. Investig., 2000, vol. 80, pp. 617–654. doi: 10.1038/labinvest.3780067
  93. Wolf A.J., Linas B., Trevejo-Nuñez G.J., Kincaid E., Tamura T., Takatsu K., Ernst J.D. Mycobacterium tuberculosis infects dendritic cells with high frequency and impairs their function in vivo. J. Immunol., 2007, vol. 179, pp. 2509–2519. doi: 10.4049/jimmunol.179.4.2509
  94. Yang C.T., Cambier C.J., Davis J.M., Hall C.J., Crosier P.S., Ramakrishnan L. Neutrophils exert protection in the early tuberculous granuloma by oxida tive killing of mycobacteria phagocytosed from infected macrophages. Cell Host Microbe, 2012, vol. 12, pp. 301–312. doi: 10.1016/j.chom.2012.07.009
  95. Yeremeev V., Linge I., Kondratieva T., Apt A. Neutrophils exacerbate tuberculosis infection in genetically susceptible mice. Tuberculosis, 2015, vol. 95, pp. 447–451. doi: 10.1016/j.tube.2015.03.007
  96. Zanetti M. Cathelicidins, multifunctional peptides of the innate immunity. J. Leukoc. Biol., 2004, vol. 75, pp. 39–48. doi: 10.1189/jlb.0403147

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