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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Emerging roles of neutrophils in immune homeostasis

  • Lee, Mingyu (Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University) ;
  • Lee, Suh Yeon (Department of Biological Sciences, Sungkyunkwan University) ;
  • Bae, Yoe-Sik (Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University)
  • Received : 2022.07.25
  • Accepted : 2022.08.23
  • Published : 2022.10.31
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Abstract

Neutrophils, the most abundant innate immune cells, play essential roles in the innate immune system. As key innate immune cells, neutrophils detect intrusion of pathogens and initiate immune cascades with their functions; swarming (arresting), cytokine production, degranulation, phagocytosis, and projection of neutrophil extracellular trap. Because of their short lifespan and consumption during immune response, neutrophils need to be generated consistently, and generation of newborn neutrophils (granulopoiesis) should fulfill the environmental/systemic demands for training in cases of infection. Accumulating evidence suggests that neutrophils also play important roles in the regulation of adaptive immunity. Neutrophil-mediated immune responses end with apoptosis of the cells, and proper phagocytosis of the apoptotic body (efferocytosis) is crucial for initial and post resolution by producing tolerogenic innate/adaptive immune cells. However, inflammatory cues can impair these cascades, resulting in systemic immune activation; necrotic/pyroptotic neutrophil bodies can aggravate the excessive inflammation, increasing inflammatory macrophage and dendritic cell activation and subsequent TH1/TH17 responses contributing to the regulation of the pathogenesis of autoimmune disease. In this review, we briefly introduce recent studies of neutrophil function as players of immune response.

Keywords

Acknowledgement

This study was supported by the Basic Science Research Program Planning through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and Future Planning (NRF-2020M3A9D3038435, NRF-2021R1A2C3011228, NRF-2017R1A5A1014560), and by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI20C0026). The figures were created with BioRender.com.

References

  1. Yvan-Charvet L and Ng LG (2019) Granulopoiesis and neutrophil homeostasis: a metabolic, daily balancing act. Trends Immunol 40, 598-612 https://doi.org/10.1016/j.it.2019.05.004
  2. Nemeth T, Sperandio M and Mocsai A (2020) Neutrophils as emerging therapeutic targets. Nat Rev Drug Discov 19, 253-275 https://doi.org/10.1038/s41573-019-0054-z
  3. Cassatella MA, Ostberg NK, Tamassia N and Soehnlein O (2019) Biological roles of neutrophil-derived granule proteins and cytokines. Trends Immunol 40, 648-664 https://doi.org/10.1016/j.it.2019.05.003
  4. Papayannopoulos V (2018) Neutrophil extracellular traps in immunity and disease. Nat Rev Immunol 18, 134-147 https://doi.org/10.1038/nri.2017.105
  5. Liew PX and Kubes P (2019) The neutrophil's role during health and disease. Physiol Rev 99, 1223-1248 https://doi.org/10.1152/physrev.00012.2018
  6. Bae GH, Kim YS, Park JY et al (2022) Unique characteristics of lung resident neutrophils are maintained by PGE2/ PKA/Tgm2-mediated signaling. Blood 140, 889-899
  7. Kolaczkowska E and Kubes P (2013) Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol 13, 159-175 https://doi.org/10.1038/nri3399
  8. Dinauer MC (2019) Inflammatory consequences of inherited disorders affecting neutrophil function. Blood 133, 2130-2139 https://doi.org/10.1182/blood-2018-11-844563
  9. Thanabalasuriar A, Scott BNV, Peiseler M et al (2019) Neutrophil extracellular traps confine pseudomonas aeruginosa ocular biofilms and restrict brain invasion. Cell Host Microbe 25, 526-536.e524 https://doi.org/10.1016/j.chom.2019.02.007
  10. Hopke A, Scherer A, Kreuzburg S et al (2020) Neutrophil swarming delays the growth of clusters of pathogenic fungi. Nat Commun 11, 2031 https://doi.org/10.1038/s41467-020-15834-4
  11. Warnatsch A, Tsourouktsoglou T-D, Branzk N et al (2017) Reactive oxygen species localization programs inflammation to clear microbes of different size. Immunity 46, 421-432 https://doi.org/10.1016/j.immuni.2017.02.013
  12. Kienle K, Glaser KM, Eickhoff S et al (2021) Neutrophils self-limit swarming to contain bacterial growth in vivo. Science 372, eabe7729 https://doi.org/10.1126/science.abe7729
  13. Margaroli C, Moncada-Giraldo D, Gulick DA et al (2021) Transcriptional firing represses bactericidal activity in cystic fibrosis airway neutrophils. Cell Rep Med 2, 100239 https://doi.org/10.1016/j.xcrm.2021.100239
  14. Branzk N, Lubojemska A, Hardison SE et al (2014) Neutrophils sense microbe size and selectively release neutrophil extracellular traps in response to large pathogens. Nat Immunol 15, 1017-1025 https://doi.org/10.1038/ni.2987
  15. Li X, Utomo A, Cullere X et al (2011) The β-glucan receptor Dectin-1 activates the integrin Mac-1 in neutrophils via vav protein signaling to promote Candida albicans clearance. Cell Host Microbe 10, 603-615 https://doi.org/10.1016/j.chom.2011.10.009
  16. Monteith AJ, Miller JM, Maxwell CN, Chazin WJ and Skaar EP (2021) Neutrophil extracellular traps enhance macrophage killing of bacterial pathogens. Sci Adv 7, eabj2101 https://doi.org/10.1126/sciadv.abj2101
  17. Castanheira FVS and Kubes P (2019) Neutrophils and NETs in modulating acute and chronic inflammation. Blood 133, 2178-2185 https://doi.org/10.1182/blood-2018-11-844530
  18. Lee SK, Kim SD, Kook M et al (2015) Phospholipase D2 drives mortality in sepsis by inhibiting neutrophil extracellular trap formation and down-regulating CXCR2. J Exp Med 212, 1381-1390 https://doi.org/10.1084/jem.20141813
  19. Enyedi B, Kala S, Nikolich-Zugich T and Niethammer P (2013) Tissue damage detection by osmotic surveillance. Nat Cell Biol 15, 1123-1130 https://doi.org/10.1038/ncb2818
  20. Ping L, Wu Y, Hosu BG, Tang JX and Berg HC (2014) Osmotic pressure in a bacterial swarm. Biophys J 107, 871-878 https://doi.org/10.1016/j.bpj.2014.05.052
  21. Diz-Munoz A, Thurley K, Chintamen S et al (2016) Membrane tension acts through PLD2 and mTORC2 to limit actin network assembly during neutrophil migration. PLoS Biol 14, e1002474 https://doi.org/10.1371/journal.pbio.1002474
  22. Manz MG and Boettcher S (2014) Emergency granulopoiesis. Nat Rev Immunol 14, 302-314 https://doi.org/10.1038/nri3660
  23. Yvan-Charvet L and Ng LG (2019) Granulopoiesis and neutrophil homeostasis: a metabolic, daily balancing act. Trends Immunol 40, 598-612 https://doi.org/10.1016/j.it.2019.05.004
  24. Boettcher S, Gerosa RC, Radpour R et al (2014) Endothelial cells translate pathogen signals into G-CSF-driven emergency granulopoiesis. Blood 124, 1393-1403 https://doi.org/10.1182/blood-2014-04-570762
  25. Danek P, Kardosova M, Janeckova L et al (2020) β-CateninTCF/LEF signaling promotes steady-state and emergency granulopoiesis via G-CSF receptor upregulation. Blood 136, 2574-2587 https://doi.org/10.1182/blood.2019004664
  26. Silva-Garcia O, Valdez-Alarcon JJ and Baizabal-Aguirre VM (2019) Wnt/β-catenin signaling as a molecular target by pathogenic bacteria. Front Immunol 10, 2135 https://doi.org/10.3389/fimmu.2019.02135
  27. Becher B, Tugues S and Greter M (2016) GM-CSF: from growth factor to central mediator of tissue inflammation. Immunity 45, 963-973 https://doi.org/10.1016/j.immuni.2016.10.026
  28. Kim HS, Park MY, Lee SK, Park JS, Lee HY and Bae YS (2018) Activation of formyl peptide receptor 2 by WKYMVm enhances emergency granulopoiesis through phospholipase C activity. BMB Rep 51, 418-423 https://doi.org/10.5483/BMBRep.2018.51.8.080
  29. Kim SD, Kim Y-K, Lee HY et al (2010) The agonists of formyl peptide receptors prevent development of severe sepsis after microbial infection. J Immunol Res 185, 4302-4310
  30. Freitas A, Alves-Filho JC, Victoni T et al (2009) IL-17 receptor signaling is required to control polymicrobial sepsis. J Immunol 182, 7846-7854 https://doi.org/10.4049/jimmunol.0803039
  31. Taylor PR, Roy S, Leal SM et al (2014) Activation of neutrophils by autocrine IL-17A-IL-17RC interactions during fungal infection is regulated by IL-6, IL-23, RORγt and dectin-2. Nat Immunol 15, 143-151 https://doi.org/10.1038/ni.2797
  32. Stark MA, Huo Y, Burcin TL, Morris MA, Olson TS and Ley K (2005) Phagocytosis of apoptotic neutrophils regulates granulopoiesis via IL-23 and IL-17. Immunity 22, 285-294 https://doi.org/10.1016/j.immuni.2005.01.011
  33. Netea MG, Dominguez-Andres J, Barreiro LB et al (2020) Defining trained immunity and its role in health and disease. Nat Rev Immunol 20, 375-388 https://doi.org/10.1038/s41577-020-0285-6
  34. Kalafati L, Kourtzelis I, Schulte-Schrepping J et al (2020) Innate immune training of granulopoiesis promotes antitumor activity. Cell 183, 771-785 e712 https://doi.org/10.1016/j.cell.2020.09.058
  35. Kalafati L, Mitroulis I, Verginis P, Chavakis T and Kourtzelis I (2020) Neutrophils as orchestrators in tumor development and metastasis formation. Front Oncol 10, 581457 https://doi.org/10.3389/fonc.2020.581457
  36. Cortez-Retamozo V, Etzrodt M, Newton A et al (2012) Origins of tumor-associated macrophages and neutrophils. Proc Natl Acad Sci U S A 109, 2491-2496 https://doi.org/10.1073/pnas.1113744109
  37. Casbon AJ, Reynaud D, Park C et al (2015) Invasive breast cancer reprograms early myeloid differentiation in the bone marrow to generate immunosuppressive neutrophils. Proc Natl Acad Sci U S A 112, E566-575
  38. Grzywa TM, Sosnowska A, Matryba P et al (2020) Myeloid cell-derived arginase in cancer immune response. Front immunol 11, 938 https://doi.org/10.3389/fimmu.2020.00938
  39. Deryugina EI, Zajac E, Juncker-Jensen A, Kupriyanova TA, Welter L and Quigley JP (2014) Tissue-infiltrating neutrophils constitute the major in vivo source of angiogenesisinducing MMP-9 in the tumor microenvironment. Neoplasia 16, 771-788 https://doi.org/10.1016/j.neo.2014.08.013
  40. Khan N, Downey J, Sanz J et al (2020) M. tuberculosis reprograms hematopoietic stem cells to limit myelopoiesis and impair trained immunity. Cell 183, 752-770 e722 https://doi.org/10.1016/j.cell.2020.09.062
  41. Ebata KO, Hashimoto D, Takahashi S, Hayase E, Ogasawara R and Teshima T (2017) Intestinal microbiota play a critical role in neutrophil engraftment posttransplant and recovery after chemotherapy by stimulating T cell Production of IL-17A. Blood 130, 3166
  42. Balmer ML, Schurch CM, Saito Y et al (2014) Microbiotaderived compounds drive steady-state granulopoiesis via MyD88/TICAM signaling. J Immunol Res 193, 5273-5283
  43. Khosravi A, Yanez A, Price Jeremy G et al (2014) Gut microbiota promote hematopoiesis to control bacterial infection. Cell Host Microbe 15, 374-381 https://doi.org/10.1016/j.chom.2014.02.006
  44. Orsini M, Chateauvieux S, Rhim J et al (2019) Sphingolipid-mediated inflammatory signaling leading to autophagy inhibition converts erythropoiesis to myelopoiesis in human hematopoietic stem/progenitor cells. Cell Death Differ 26, 1796-1812 https://doi.org/10.1038/s41418-018-0245-x
  45. Riffelmacher T, Clarke A, Richter FC et al (2017) Autophagy-dependent generation of free fatty acids is critical for normal neutrophil differentiation. Immunity 47, 466-480 e465 https://doi.org/10.1016/j.immuni.2017.08.005
  46. Rozman S, Yousefi S, Oberson K, Kaufmann T, Benarafa C and Simon HU (2015) The generation of neutrophils in the bone marrow is controlled by autophagy. Cell Death Differ 22, 445-456 https://doi.org/10.1038/cdd.2014.169
  47. Moorlag SJCFM, Rodriguez-Rosales YA, Gillard J et al (2020) BCG vaccination induces long-term functional reprogramming of human neutrophils. Cell Rep 33, 108387 https://doi.org/10.1016/j.celrep.2020.108387
  48. Lin R, Yi Z, Wang J, Geng S and Li L (2022) Generation of resolving memory neutrophils through pharmacological training with 4-PBA or genetic deletion of TRAM. Cell Death Dis 13, 345 https://doi.org/10.1038/s41419-022-04809-6
  49. de Bree LCJ, Mourits VP, Koeken VA et al (2020) Circadian rhythm influences induction of trained immunity by BCG vaccination. J Clin Invest 130, 5603-5617 https://doi.org/10.1172/JCI133934
  50. Casanova-Acebes M, Nicolas-Avila JA, Li JL et al (2018) Neutrophils instruct homeostatic and pathological states in naive tissues. J Exp Med 215, 2778-2795 https://doi.org/10.1084/jem.20181468
  51. Zhang D and Frenette PS (2019) Cross talk between neutrophils and the microbiota. Blood 133, 2168-2177 https://doi.org/10.1182/blood-2018-11-844555
  52. Rankin SM (2010) The bone marrow: a site of neutrophil clearance. J Leukoc Biol 88, 241-251 https://doi.org/10.1189/jlb.0210112
  53. Wang J, Hossain M, Thanabalasuriar A, Gunzer M, Meininger C and Kubes P (2017) Visualizing the function and fate of neutrophils in sterile injury and repair. Science 358, 111-116 https://doi.org/10.1126/science.aam9690
  54. Doran AC, Yurdagul A and Tabas I (2020) Efferocytosis in health and disease. Nat Rev Immunol 20, 254-267 https://doi.org/10.1038/s41577-019-0240-6
  55. Farrera C and Fadeel B (2013) Macrophage clearance of neutrophil extracellular traps is a silent process. J Immunol 191, 2647-2656 https://doi.org/10.4049/jimmunol.1300436
  56. Ampomah PB, Cai B, Sukka SR et al (2022) Macrophages use apoptotic cell-derived methionine and DNMT3A during efferocytosis to promote tissue resolution. Nat Metab 4, 444-457 https://doi.org/10.1038/s42255-022-00551-7
  57. Gerlach BD, Ampomah PB, Yurdagul A Jr et al (2021) Efferocytosis induces macrophage proliferation to help resolve tissue injury. Cell Metab 33, 2445-2463 e2448 https://doi.org/10.1016/j.cmet.2021.10.015
  58. Kourtzelis I, Li X, Mitroulis I et al (2019) DEL-1 promotes macrophage efferocytosis and clearance of inflammation. Nat Immunol 20, 40-49 https://doi.org/10.1038/s41590-018-0249-1
  59. Schmid M, Gemperle C, Rimann N and Hersberger M (2016) Resolvin D1 polarizes primary human macrophages toward a proresolution phenotype through GPR32. J Immunol 196, 3429-3437 https://doi.org/10.4049/jimmunol.1501701
  60. Fredman G, Ozcan L, Spolitu S et al (2014) Resolvin D1 limits 5-lipoxygenase nuclear localization and leukotriene B4 synthesis by inhibiting a calcium-activated kinase pathway. Proc Natl Acad Sci U.S.A 111, 14530-14535 https://doi.org/10.1073/pnas.1410851111
  61. Arnardottir H, Thul S, Pawelzik SC et al (2021) The resolvin D1 receptor GPR32 transduces inflammation resolution and atheroprotection. J Clin Invest 131, e142883 https://doi.org/10.1172/JCI142883
  62. Luo B, Han F, Xu K et al (2016) Resolvin D1 Programs inflammation resolution by increasing TGF-β expression induced by dying cell clearance in experimental autoimmune neuritis. J Neurosci 36, 9590-9603 https://doi.org/10.1523/JNEUROSCI.0020-16.2016
  63. Yuan J, Lin F, Chen L et al (2022) Lipoxin A4 regulates M1/M2 macrophage polarization via FPR2-IRF pathway. Inflammopharmacology 30, 487-498 https://doi.org/10.1007/s10787-022-00942-y
  64. Prieto P, Cuenca J, Traves PG, Fernandez-Velasco M, Martin-Sanz P and Bosca L (2010) Lipoxin A4 impairment of apoptotic signaling in macrophages: implication of the PI3K/Akt and the ERK/Nrf-2 defense pathways. Cell Death Differ 17, 1179-1188 https://doi.org/10.1038/cdd.2009.220
  65. Godson C, Mitchell S, Harvey K, Petasis NA, Hogg N and Brady HR (2000) Cutting edge: lipoxins rapidly stimulate nonphlogistic phagocytosis of apoptotic neutrophils by monocyte-derived macrophages. J Immunol 164, 1663-1667 https://doi.org/10.4049/jimmunol.164.4.1663
  66. Son M, Porat A, He M et al (2016) C1q and HMGB1 reciprocally regulate human macrophage polarization. Blood 128, 2218-2228
  67. Benoit ME, Clarke EV, Morgado P, Fraser DA and Tenner AJ (2012) Complement protein C1q directs macrophage polarization and limits inflammasome activity during the uptake of apoptotic cells. J Immunol 188, 5682-5693 https://doi.org/10.4049/jimmunol.1103760
  68. Tran MTN, Hamada M, Jeon H et al (2017) MafB is a critical regulator of complement component C1q. Nat Commun 8, 1700 https://doi.org/10.1038/s41467-017-01711-0
  69. Croker BA, Metcalf D, Robb L et al (2004) SOCS3 is a critical physiological negative regulator of G-CSF signaling and emergency granulopoiesis. Immunity 20, 153-165 https://doi.org/10.1016/S1074-7613(04)00022-6
  70. Lee CK, Raz R, Gimeno R et al (2002) STAT3 is a negative regulator of granulopoiesis but is not required for GCSF-dependent differentiation. Immunity 17, 63-72 https://doi.org/10.1016/S1074-7613(02)00336-9
  71. Hutchins AP, Diez D and Miranda-Saavedra D (2013) The IL-10/STAT3-mediated anti-inflammatory response: recent developments and future challenges. Brief Funct Genom 12, 489-498 https://doi.org/10.1093/bfgp/elt028
  72. Morris R, Kershaw NJ and Babon JJ (2018) The molecular details of cytokine signaling via the JAK/STAT pathway. Protein Sci 27, 1984-2009 https://doi.org/10.1002/pro.3519
  73. Clarke EV, Weist BM, Walsh CM and Tenner AJ (2015) Complement protein C1q bound to apoptotic cells suppresses human macrophage and dendritic cell-mediated Th17 and Th1 T cell subset proliferation. J Leukoc Biol 97, 147-160 https://doi.org/10.1189/jlb.3A0614-278R
  74. Fullerton JN and Gilroy DW (2016) Resolution of inflammation: a new therapeutic frontier. Nat Rev Drug Discov 15, 551-567 https://doi.org/10.1038/nrd.2016.39
  75. Roncarolo MG, Gregori S, Bacchetta R, Battaglia M and Gagliani N (2018) The biology of T regulatory type 1 cells and their therapeutic application in immune-mediated diseases. Immunity 49, 1004-1019 https://doi.org/10.1016/j.immuni.2018.12.001
  76. Lewkowicz N, Mycko MP, Przygodzka P et al (2016) Induction of human IL-10-producing neutrophils by LPS-stimulated Treg cells and IL-10. Mucosal Immunol 9, 364-378 https://doi.org/10.1038/mi.2015.66
  77. Khoyratty TE, Ai Z, Ballesteros I et al (2021) Distinct transcription factor networks control neutrophil-driven inflammation. Nat Immunol 22, 1093-1106 https://doi.org/10.1038/s41590-021-00968-4
  78. Wang X, Cai J, Lin B et al (2021) GPR34-mediated sensing of lysophosphatidylserine released by apoptotic neutrophils activates type 3 innate lymphoid cells to mediate tissue repair. Immunity 54, 1123-1136.e1128 https://doi.org/10.1016/j.immuni.2021.05.007
  79. Fischer A, Wannemacher J, Christ S et al (2022) Neutrophils direct preexisting matrix to initiate repair in damaged tissues. Nat Immunol 23, 518-531 https://doi.org/10.1038/s41590-022-01166-6
  80. Lim K, Hyun YM, Lambert-Emo K et al (2015) Neutrophil trails guide influenza-specific CD8+ T cells in the airways. Science 349, aaa4352 https://doi.org/10.1126/science.aaa4352
  81. Vono M, Lin A, Norrby-Teglund A, Koup RA, Liang F and Lore K (2017) Neutrophils acquire the capacity for antigen presentation to memory CD4+ T cells in vitro and ex vivo. Blood 129, 1991-2001 https://doi.org/10.1182/blood-2016-10-744441
  82. Marini O, Costa S, Bevilacqua D et al (2017) Mature CD10+ and immature CD10- neutrophils present in G-CSFtreated donors display opposite effects on T cells. Blood 129, 1343-1356 https://doi.org/10.1182/blood-2016-04-713206
  83. Mysore V, Cullere X, Mears J et al (2021) FcγR engagement reprograms neutrophils into antigen cross-presenting cells that elicit acquired anti-tumor immunity. Nat Commun 12, 4791 https://doi.org/10.1038/s41467-021-24591-x
  84. Lu T, Kobayashi SD, Quinn MT and Deleo FR (2012) A NET outcome. Front Immunol 3, 365
  85. Bedoui S, Herold MJ and Strasser A (2020) Emerging connectivity of programmed cell death pathways and its physiological implications. Nat Rev Mol Cell Biol 21, 678-695 https://doi.org/10.1038/s41580-020-0270-8
  86. Brostjan C and Oehler R (2020) The role of neutrophil death in chronic inflammation and cancer. Cell Death Discov 6, 26 https://doi.org/10.1038/s41420-020-0255-6
  87. Li P, Jiang M, Li K et al (2021) Glutathione peroxidase 4-regulated neutrophil ferroptosis induces systemic autoimmunity. Nat Immunol 22, 1107-1117 https://doi.org/10.1038/s41590-021-00993-3
  88. Lagasse E and Weissman IL (1994) bcl-2 inhibits apoptosis of neutrophils but not their engulfment by macrophages. J Exp Med 179, 1047-1052 https://doi.org/10.1084/jem.179.3.1047
  89. Zhao X, Yang L, Chang N et al (2020) Neutrophils undergo switch of apoptosis to NETosis during murine fatty liver injury via S1P receptor 2 signaling. Cell Death Dis 11, 379 https://doi.org/10.1038/s41419-020-2582-1
  90. Yang Y, Wang Y, Guo L, Gao W, Tang T-L and Yan M (2022) Interaction between macrophages and ferroptosis. Cell Death Dis 13, 355 https://doi.org/10.1038/s41419-022-04775-z
  91. Chen K, Murao A, Arif A et al (2021) Inhibition of efferocytosis by extracellular CIRP-Induced neutrophil extracellular traps. J Immunol 206, 797-806 https://doi.org/10.4049/jimmunol.2000091
  92. Chen L, Zhao Y, Lai D et al (2018) Neutrophil extracellular traps promote macrophage pyroptosis in sepsis. Cell Death Dis 9, 597 https://doi.org/10.1038/s41419-018-0538-5
  93. Decout A, Katz JD, Venkatraman S and Ablasser A (2021) The cGAS-STING pathway as a therapeutic target in inflammatory diseases. Nat Rev Immunol 21, 548-569 https://doi.org/10.1038/s41577-021-00524-z
  94. Apel F, Andreeva L, Knackstedt LS et al (2021) The cytosolic DNA sensor cGAS recognizes neutrophil extracellular traps. Sci Signal 14, eaax7942 https://doi.org/10.1126/scisignal.aax7942
  95. Boada-Romero E, Martinez J, Heckmann BL and Green DR (2020) The clearance of dead cells by efferocytosis. Nat Rev Mol Cell Biol 21, 398-414
  96. van Gisbergen KP, Sanchez-Hernandez M, Geijtenbeek TB and van Kooyk Y (2005) Neutrophils mediate immune modulation of dendritic cells through glycosylation-dependent interactions between Mac-1 and DC-SIGN. J Exp Med 201, 1281-1292 https://doi.org/10.1084/jem.20041276
  97. Steinman RM, Turley S, Mellman I and Inaba K (2000) The induction of tolerance by dendritic cells that have captured apoptotic cells. J Exp Med 191, 411-416 https://doi.org/10.1084/jem.191.3.411
  98. Sangaletti S, Tripodo C, Chiodoni C et al (2012) Neutrophil extracellular traps mediate transfer of cytoplasmic neutrophil antigens to myeloid dendritic cells toward ANCA induction and associated autoimmunity. Blood 120, 3007-3018 https://doi.org/10.1182/blood-2012-03-416156
  99. Fresneda Alarcon M, McLaren Z and Wright HL (2021) Neutrophils in the pathogenesis of rheumatoid arthritis and systemic lupus erythematosus: same foe different M.O. Front Immunol 12, 649693 https://doi.org/10.3389/fimmu.2021.649693