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Neutrophils

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Immunology of the Skin

Abstract

Neutrophils are essential components of the innate immune system. They participate in a variety of tissue reactions, including antimicrobial responses and damage repair. Neutrophils are exquisitely sensitive to migratory stimuli, which enables them to rapidly home into injured tissues, including the skin, where they exert their effector functions. The latter include the release of preformed mediators from granules, production of reactive oxygen species, and release of DNA traps into the extracellular space. Based on these activities, neutrophils play a crucial role in cutaneous immune responses, and patients with neutrophil defects are prone to bacterial and fungal skin infections. Nevertheless, neutrophils may also directly cause tissue damage, and are the driving force behind the pathology of a number of inflammatory skin conditions. This chapter describes the molecular mechanisms underlying neutrophil function in the skin, and reviews our current understanding of the role of neutrophils in cutaneous biology and disease.

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References

  1. Abadie V, Badell E, Douillard P, Ensergueix D, Leenen PJ, Tanguy M, Fiette L, Saeland S, Gicquel B, Winter N (2005) Neutrophils rapidly migrate via lymphatics after Mycobacterium bovis BCG intradermal vaccination and shuttle live bacilli to the draining lymph nodes. Blood 106(5):1843–1850

    Article  CAS  PubMed  Google Scholar 

  2. Amulic B, Cazalet C, Hayes GL, Metzler KD, Zychlinsky A (2012) Neutrophil function: from mechanisms to disease. Annu Rev Immunol 30:459–489

    Article  CAS  PubMed  Google Scholar 

  3. An J-H, Kurokawa K, Jung D-J, Kim M-J, Kim C-H, Fujimoto Y, Fukase K, Coggeshall KM, Lee BL (2013) Human SAP is a novel peptidoglycan recognition protein that induces complement-independent phagocytosis of Staphylococcus aureus. J Immunol 191(6):3319–3327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Barbosa MD, Nguyen QA, Tchernev VT, Ashley JA, Detter JC, Blaydes SM, Brandt SJ, Chotai D, Hodgman C, Solari RC, Lovett M, Kingsmore SF (1996) Identification of the homologous beige and Chediak-Higashi syndrome genes. Nature 382(6588):262–265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Beauvillain C, Cunin P, Doni A, Scotet M, Jaillon S, Loiry ML, Magistrelli G, Masternak K, Chevailler A, Delneste Y, Jeannin P (2011) CCR7 is involved in the migration of neutrophils to lymph nodes. Blood 117(4):1196–1204

    Article  CAS  PubMed  Google Scholar 

  6. Beauvillain C, Delneste Y, Scotet M, Peres A, Gascan H, Guermonprez P, Barnaba V, Jeannin P (2007) Neutrophils efficiently cross-prime naive T cells in vivo. Blood 110(8):2965–2973

    Article  CAS  PubMed  Google Scholar 

  7. Bedard K, Krause K-H (2007) The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 87(1):245–313

    Article  CAS  PubMed  Google Scholar 

  8. Belaaouaj A, Kim KS, Shapiro SD (2000) Degradation of outer membrane protein A in Escherichia coli killing by neutrophil elastase. Science 289(5482):1185

    Article  CAS  PubMed  Google Scholar 

  9. Bergers G, Brekken R, McMahon G, Vu TH, Itoh T, Tamaki K, Tanzawa K, Thorpe P, Itohara S, Werb Z, Hanahan D (2000) Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol 2(10):737–744

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Bodey GP, Buckley M, Sathe YS, Freireich EJ (1966) Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia. Ann Intern Med 64(2):328–340

    Article  CAS  PubMed  Google Scholar 

  11. Bonneau M, Epardaud M, Payot F, Niborski V, Thoulouze MI, Bernex F, Charley B, Riffault S, Guilloteau LA, Schwartz-Cornil I (2006) Migratory monocytes and granulocytes are major lymphatic carriers of Salmonella from tissue to draining lymph node. J Leukoc Biol 79(2):268–276

    Article  CAS  PubMed  Google Scholar 

  12. Borregaard N (2010) Neutrophils, from marrow to microbes. Immunity 33(5):657–670

    Article  CAS  PubMed  Google Scholar 

  13. Boxio R, Bossenmeyer-Pourie C, Steinckwich N, Dournon C, Nusse O (2004) Mouse bone marrow contains large numbers of functionally competent neutrophils. J Leukoc Biol 75(4):604–611

    Article  CAS  PubMed  Google Scholar 

  14. Brackett CM, Muhitch JB, Evans SS, Gollnick SO (2013) IL-17 promotes neutrophil entry into tumor-draining lymph nodes following induction of sterile inflammation. J Immunol 8:4348–4357

    Article  CAS  Google Scholar 

  15. Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, Weinrauch Y, Zychlinsky A (2004) Neutrophil extracellular traps kill bacteria. Science 303(5663):1532–1535

    Article  CAS  PubMed  Google Scholar 

  16. Brinkmann V, Zychlinsky A (2007) Beneficial suicide: why neutrophils die to make NETs. Nat Rev Microbiol 5(8):577–582

    Article  CAS  PubMed  Google Scholar 

  17. Brooklyn TN, Dunnill MGS, Shetty A, Bowden JJ, Williams JDL, Griffiths CEM, Forbes A, Greenwood R, Probert CS (2006) Infliximab for the treatment of pyoderma gangrenosum: a randomised, double blind, placebo controlled trial. Gut 55(4):505–509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Carlin LM, Stamatiades EG, Auffray C, Hanna RN, Glover L, Vizcay-Barrena G, Hedrick CC, Cook HT, Diebold S, Geissmann F (2013) Nr4a1-dependent Ly6C(low) monocytes monitor endothelial cells and orchestrate their disposal. Cell 153(2):362–375

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Carlson JA (2010) The histological assessment of cutaneous vasculitis. Histopathology 56(1):3–23

    Article  PubMed  Google Scholar 

  20. Casanova-Acebes M, Pitaval C, Weiss LA, Nombela-Arrieta C, Chevre R, AG N, Kunisaki Y, Zhang D, van Rooijen N, Silberstein LE, Weber C, Nagasawa T, Frenette PS, Castrillo A, Hidalgo A (2013) Rhythmic modulation of the hematopoietic niche through neutrophil clearance. Cell 153(5):1025–1035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Cederlund A, Agerberth B, Bergman P (2010) Specificity in killing pathogens is mediated by distinct repertoires of human neutrophil peptides. J Innate Immun 2(6):508–521

    Article  CAS  PubMed  Google Scholar 

  22. Cho JS, Guo Y, Ramos RI, Hebroni F, Plaisier SB, Xuan C, Granick JL, Matsushima H, Takashima A, Iwakura Y, Cheung AL, Cheng G, Lee DJ, Simon SI, Miller LS (2012) Neutrophil-derived IL-1β is sufficient for abscess formation in immunity against Staphylococcus aureus in mice. PLoS Pathog 8(11):e1003047

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Cho JS, Pietras EM, Garcia NC, Ramos RI, Farzam DM, Monroe HR, Magorien JE, Blauvelt A, Kolls JK, Cheung AL, Cheng G, Modlin RL, Miller LS (2010) IL-17 is essential for host defense against cutaneous Staphylococcus aureus infection in mice. J Clin Invest 120(5):1762–1773

    Article  PubMed  PubMed Central  Google Scholar 

  24. Cho JS, Zussman J, Donegan NP, Ramos RI, Garcia NC, Uslan DZ, Iwakura Y, Simon SI, Cheung AL, Modlin RL, Kim J, Miller LS (2011) Noninvasive in vivo imaging to evaluate immune responses and antimicrobial therapy against Staphylococcus aureus and USA300 MRSA skin infections. J Invest Dermatol 131(4):907–915

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Christoffersson G, Vagesjo E, Vandooren J, Liden M, Massena S, Reinert RB, Brissova M, Powers AC, Opdenakker G, Phillipson M (2012) VEGF-A recruits a proangiogenic MMP-9-delivering neutrophil subset that induces angiogenesis in transplanted hypoxic tissue. Blood 120(23):4653–4662

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Christopher MJ, Link DC (2008) Granulocyte colony-stimulating factor induces osteoblast apoptosis and inhibits osteoblast differentiation. J Bone Miner Res 23(11):1765–1774

    Article  PubMed  PubMed Central  Google Scholar 

  27. Cohen PR (2007) Sweet’s syndrome – a comprehensive review of an acute febrile neutrophilic dermatosis. Orphanet J Rare Dis 2(34):26

    Google Scholar 

  28. Cohen PR (2009) Neutrophilic dermatoses: a review of current treatment options. Am J Clin Dermatol 10(5):301–312

    Article  PubMed  Google Scholar 

  29. Corbin BD, Seeley EH, Raab A, Feldmann J, Miller MR, Torres VJ, Anderson KL, Dattilo BM, Dunman PM, Gerads R, Caprioli RM, Nacken W, Chazin WJ, Skaar EP (2008) Metal chelation and inhibition of bacterial growth in tissue abscesses. Science 319(5865):962–965

    Article  CAS  PubMed  Google Scholar 

  30. Craven RR, Gao X, Allen IC, Gris D, Bubeck Wardenburg J, McElvania-Tekippe E, Ting JP, Duncan JA (2009) Staphylococcus aureus alpha-hemolysin activates the NLRP3-inflammasome in human and mouse monocytic cells. PLoS One 4(10):0007446

    Article  CAS  Google Scholar 

  31. Dancey JT, Deubelbeiss KA, Harker LA, Finch CA (1976) Neutrophil kinetics in man. J Clin Invest 58(3):705–715

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Davies MJ, Hawkins CL, Pattison DI, Rees MD (2008) Mammalian heme peroxidases: from molecular mechanisms to health implications. Antioxid Redox Signal 10(7):1199–1234

    Article  CAS  PubMed  Google Scholar 

  33. Donabedian H, Gallin JI (1983) The hyperimmunoglobulin E recurrent-infection (Job’s) syndrome: a review of the NIH experience and the literature. Medicine 62(4):195–208

    Article  CAS  PubMed  Google Scholar 

  34. Donadieu J, Fenneteau O, Beaupain B, Mahlaoui N, Chantelot CB (2011) Congenital neutropenia: diagnosis, molecular bases and patient management. Orphanet J Rare Dis 6:26

    Article  PubMed  PubMed Central  Google Scholar 

  35. Eash KJ, Greenbaum AM, Gopalan PK, Link DC (2010) CXCR2 and CXCR4 antagonistically regulate neutrophil trafficking from murine bone marrow. J Clin Invest 120(7):2423–2431

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Ellson CD, Davidson K, Ferguson GJ, O’Connor R, Stephens LR, Hawkins PT (2006) Neutrophils from p40phox-/- mice exhibit severe defects in NADPH oxidase regulation and oxidant-dependent bacterial killing. J Exp Med 203(8):1927–1937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Fahmy M, Ramamoorthy S, Hata T, Sandborn WJ (2012) Ustekinumab for peristomal pyoderma gangrenosum. Am J Gastroenterol 107(5):794–795

    Article  CAS  PubMed  Google Scholar 

  38. Fischer-Stabauer M, Boehner A, Eyerich S, Carbone T, Traidl-Hoffmann C, Schmidt-Weber CB, Cavani A, Ring J, Hein R, Eyerich K (2012) Differential in situ expression of IL-17 in skin diseases. Eur J Dermatol 22(6):781–784

    CAS  PubMed  Google Scholar 

  39. Flo TH, Smith KD, Sato S, Rodriguez DJ, Holmes MA, Strong RK, Akira S, Aderem A (2004) Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature 432(7019):917–921

    Article  CAS  PubMed  Google Scholar 

  40. Fuchs TA, Abed U, Goosmann C, Hurwitz R, Schulze I, Wahn V, Weinrauch Y, Brinkmann V, Zychlinsky A (2007) Novel cell death program leads to neutrophil extracellular traps. J Cell Biol 176(2):231–241

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Furze RC, Rankin SM (2008) The role of the bone marrow in neutrophil clearance under homeostatic conditions in the mouse. FASEB J 22(9):3111–3119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Futosi K, Fodor S, Mocsai A (2013) Neutrophil cell surface receptors and their intracellular signal transduction pathways. Int Immunopharmacol 17(3):638–650

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Gallo RL, Hooper LV (2012) Epithelial antimicrobial defence of the skin and intestine. Nat Rev Immunol 12(7):503–516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Ganz T (2003) Defensins: antimicrobial peptides of innate immunity. Nat Rev Immunol 3(9):710–720

    Article  CAS  PubMed  Google Scholar 

  45. Ganz T, Gabayan V, Liao H-I, Liu L, Oren A, Graf T, Cole AM (2003) Increased inflammation in lysozyme M-deficient mice in response to Micrococcus luteus and its peptidoglycan. Blood 101(6):2388–2392

    Article  CAS  PubMed  Google Scholar 

  46. Giasuddin ASM, El-Orfi AHAM, Ziu MM, El-Barnawi NY (1998) Sweet’s syndrome: is the pathogenesis mediated by helper T cell type 1 cytokines? J Am Acad Dermatol 39(6):940–943

    Article  CAS  PubMed  Google Scholar 

  47. Goodridge HS, Reyes CN, Becker CA, Katsumoto TR, Ma J, Wolf AJ, Bose N, Chan ASH, Magee AS, Danielson ME, Weiss A, Vasilakos JP, Underhill DM (2011) Activation of the innate immune receptor Dectin-1 upon formation of a ‘phagocytic synapse’. Nature 472(7344):471–475

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Grimbacher B, Holland SM, Gallin JI, Greenberg F, Hill SC, Malech HL, Miller JA, O’Connell AC, Puck JM (1999) Hyper-IgE syndrome with recurrent infections – an autosomal dominant multisystem disorder. N Engl J Med 340(9):692–702

    Article  CAS  PubMed  Google Scholar 

  49. Guenova E, Teske A, Fehrenbacher B, Hoerber S, Adamczyk A, Schaller M, Hoetzenecker W, Biedermann T (2011) Interleukin 23 expression in pyoderma gangrenosum and targeted therapy with ustekinumab. Arch Dermatol 147(10):1203–1205

    Article  PubMed  Google Scholar 

  50. Hall JG, Morris B (1965) The origin of the cells in the efferent lymph from a single lymph node. J Exp Med 121:901–910

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Hanna S, Etzioni A (2012) Leukocyte adhesion deficiencies. Ann N Y Acad Sci 1250:50–55

    Article  CAS  PubMed  Google Scholar 

  52. Heath TJ, Lascelles AK, Morris B (1962) The cells of sheep lymph. J Anat 96:397–408

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Heath WR, Carbone FR (2013) The skin-resident and migratory immune system in steady state and memory: innate lymphocytes, dendritic cells and T cells. Nat Immunol 14(10):978–985

    Article  CAS  PubMed  Google Scholar 

  54. Heyworth PG, Cross AR, Curnutte JT (2003) Chronic granulomatous disease. Curr Opin Immunol 15(5):578–584

    Article  CAS  PubMed  Google Scholar 

  55. Hruz P, Zinkernagel AS, Jenikova G, Botwin GJ, Hugot JP, Karin M, Nizet V, Eckmann L (2009) NOD2 contributes to cutaneous defense against Staphylococcus aureus through alpha-toxin-dependent innate immune activation. Proc Natl Acad Sci U S A 106(31):12873–12878

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Ishigame H, Kakuta S, Nagai T, Kadoki M, Nambu A, Komiyama Y, Fujikado N, Tanahashi Y, Akitsu A, Kotaki H, Sudo K, Nakae S, Sasakawa C, Iwakura Y (2009) Differential roles of interleukin-17A and -17F in host defense against mucoepithelial bacterial infection and allergic responses. Immunity 30(1):108–119

    Article  CAS  PubMed  Google Scholar 

  57. Jackson SH, Gallin JI, Holland SM (1995) The p47phox mouse knock-out model of chronic granulomatous disease. J Exp Med 182(3):751–758

    Article  CAS  PubMed  Google Scholar 

  58. Jain R, Weninger W (2013) Shedding light on cutaneous innate immune responses: the intravital microscopy approach. Immunol Cell Biol 91(4):263–270

    Article  CAS  PubMed  Google Scholar 

  59. Jennette JC, Falk RJ (1997) Small-vessel vasculitis. N Engl J Med 337(21):1512–1523

    Article  CAS  PubMed  Google Scholar 

  60. Johnston B, Kubes P (1999) The alpha4-integrin: an alternative pathway for neutrophil recruitment? Immunol Today 20(12):545–550

    Article  CAS  PubMed  Google Scholar 

  61. Jung D-J, An J-H, Kurokawa K, Jung Y-C, Kim M-J, Aoyagi Y, Matsushita M, Takahashi S, Lee H-S, Takahashi K, Lee BL (2012) Specific serum Ig recognizing Staphylococcal wall teichoic acid induces complement-mediated opsonophagocytosis against Staphylococcus aureus. J Immunol 189(10):4951–4959

    Article  CAS  PubMed  Google Scholar 

  62. Kennedy AD, DeLeo FR (2009) Neutrophil apoptosis and the resolution of infection. Immunol Res 43(1–3):25–61

    Article  PubMed  Google Scholar 

  63. Kerrigan AM, Dennehy KM, Mourão-Sá D, Faro-Trindade I, Willment JA, Taylor PR, Eble JA, Brown GD, Reis e Sousa C, Brown GD (2009) CLEC-2 is a phagocytic activation receptor expressed on murine peripheral blood neutrophils. J Immunol 182(7):4150–4157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Kolaczkowska E, Kubes P (2013) Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol 13(3):159–175

    Article  CAS  PubMed  Google Scholar 

  65. Kolls JK, Linden A (2004) Interleukin-17 family members and inflammation. Immunity 21(4):467–476

    Article  CAS  PubMed  Google Scholar 

  66. Kubes P, Hunter J, Granger DN (1992) Ischemia/reperfusion-induced feline intestinal dysfunction: importance of granulocyte recruitment. Gastroenterology 103(3):807–812

    CAS  PubMed  Google Scholar 

  67. Lammermann T, Afonso PV, Angermann BR, Wang JM, Kastenmuller W, Parent CA, Germain RN (2013) Neutrophil swarms require LTB4 and integrins at sites of cell death in vivo. Nature 498(7454):371–375

    Article  PubMed  CAS  Google Scholar 

  68. Levy O, Martin S, Eichenwald E, Ganz T, Valore E, Carroll SF, Lee K, Goldmann D, Thorne GM (1999) Impaired innate immunity in the newborn: newborn neutrophils are deficient in bactericidal/permeability-increasing protein. Pediatrics 104(6):1327–1333

    Article  CAS  PubMed  Google Scholar 

  69. Ley K, Laudanna C, Cybulsky MI, Nourshargh S (2007) Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol 7(9):678–689

    Article  CAS  PubMed  Google Scholar 

  70. Ley K, Smith E, Stark MA (2006) IL-17A-producing neutrophil-regulatory Tn lymphocytes. Immunol Res 34(3):229–242

    Article  CAS  PubMed  Google Scholar 

  71. Li JL, Ng LG (2012) Peeking into the secret life of neutrophils. Immunol Res 53(1–3):168–181

    Article  CAS  PubMed  Google Scholar 

  72. Lim J, Hotchin NA (2012) Signalling mechanisms of the leukocyte integrin αMβ2: current and future perspectives. Biol Cell 104(11):631–640

    Article  CAS  PubMed  Google Scholar 

  73. Maletto BA, Ropolo AS, Alignani DO, Liscovsky MV, Ranocchia RP, Moron VG, Pistoresi-Palencia MC (2006) Presence of neutrophil-bearing antigen in lymphoid organs of immune mice. Blood 108(9):3094–3102

    Article  CAS  PubMed  Google Scholar 

  74. Malka R, Wolach B, Gavrieli R, Shochat E, Rom-Kedar V (2012) Evidence for bistable bacteria-neutrophil interaction and its clinical implications. J Clin Invest 122(8):3002–3011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Mandell GL, Hook EW (1969) Leukocyte bactericidal activity in chronic granulomatous disease: correlation of bacterial hydrogen peroxide production and susceptibility to intracellular killing. J Bacteriol 100(1):531–532

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Martin C, Burdon PC, Bridger G, Gutierrez-Ramos JC, Williams TJ, Rankin SM (2003) Chemokines acting via CXCR2 and CXCR4 control the release of neutrophils from the bone marrow and their return following senescence. Immunity 19(4):583–593

    Article  CAS  PubMed  Google Scholar 

  77. Marzano AV, Cugno M, Trevisan V, Fanoni D, Venegoni L, Berti E, Crosti C (2010) Role of inflammatory cells, cytokines and matrix metalloproteinases in neutrophil-mediated skin diseases. Clin Exp Immunol 162(1):100–107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Masson PL, Heremans JF, Schonne E (1969) Lactoferrin, an iron-binding protein in neutrophilic leukocytes. J Exp Med 130(3):643–658

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. McDonald B, Pittman K, Menezes GB, Hirota SA, Slaba I, Waterhouse CC, Beck PL, Muruve DA, Kubes P (2010) Intravascular danger signals guide neutrophils to sites of sterile inflammation. Science 330(6002):362–366

    Article  CAS  PubMed  Google Scholar 

  80. Metzler KD, Fuchs TA, Nauseef WM, Reumaux D, Roesler J, Schulze I, Wahn V, Papayannopoulos V, Zychlinsky A (2011) Myeloperoxidase is required for neutrophil extracellular trap formation: implications for innate immunity. Blood 117(3):953–959

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Miller LS, O’Connell RM, Gutierrez MA, Pietras EM, Shahangian A, Gross CE, Thirumala A, Cheung AL, Cheng G, Modlin RL (2006) MyD88 mediates neutrophil recruitment initiated by IL-1R but not TLR2 activation in immunity against Staphylococcus aureus. Immunity 24(1):79–91

    Article  CAS  PubMed  Google Scholar 

  82. Miller LS, Pietras EM, Uricchio LH, Hirano K, Rao S, Lin H, O’Connell RM, Iwakura Y, Cheung AL, Cheng G, Modlin RL (2007) Inflammasome-mediated production of IL-1beta is required for neutrophil recruitment against Staphylococcus aureus in vivo. J Immunol 179(10):6933–6942

    Article  CAS  PubMed  Google Scholar 

  83. Minegishi Y (2009) Hyper-IgE syndrome. Curr Opin Immunol 21(5):487–492

    Article  CAS  PubMed  Google Scholar 

  84. Mitchell AJ, Edwards MR, Collins AM (2001) Valency or wahlency: is the epitope diversity of the B-cell response regulated or chemically determined? Immunol Cell Biol 79(5):507–511

    Article  CAS  PubMed  Google Scholar 

  85. Molne L, Verdrengh M, Tarkowski A (2000) Role of neutrophil leukocytes in cutaneous infection caused by Staphylococcus aureus. Infect Immun 68(11):6162–6167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Munoz-Planillo R, Franchi L, Miller LS, Nunez G (2009) A critical role for hemolysins and bacterial lipoproteins in Staphylococcus aureus-induced activation of the Nlrp3 inflammasome. J Immunol 183(6):3942–3948

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Myles IA, Fontecilla NM, Valdez PA, Vithayathil PJ, Naik S, Belkaid Y, Ouyang W, Datta SK (2013) Signaling via the IL-20 receptor inhibits cutaneous production of IL-1beta and IL-17A to promote infection with methicillin-resistant Staphylococcus aureus. Nat Immunol 14(8):804–811

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Nathan C (2006) Neutrophils and immunity: challenges and opportunities. Nat Rev Immunol 6(3):173–182

    Article  CAS  PubMed  Google Scholar 

  89. Nauseef WM (2007) How human neutrophils kill and degrade microbes: an integrated view. Immunol Rev 219(1):88–102

    Article  CAS  PubMed  Google Scholar 

  90. Ng LG, Qin JS, Roediger B, Wang Y, Jain R, Cavanagh LL, Smith AL, Jones CA, de Veer M, Grimbaldeston MA, Meeusen EN, Weninger W (2011) Visualizing the neutrophil response to sterile tissue injury in mouse dermis reveals a three-phase cascade of events. J Invest Dermatol 131(10):2058–2068

    Article  CAS  PubMed  Google Scholar 

  91. Otto BR, Verweij-van Vught AMJJ, MacLaren DM (1992) Transferrins and heme-compounds as iron sources for pathogenic bacteria. Crit Rev Microbiol 18(3):217–233

    Article  CAS  PubMed  Google Scholar 

  92. Oyoshi MK, He R, Li Y, Mondal S, Yoon J, Afshar R, Chen M, Lee DM, Luo HR, Luster AD, Cho JS, Miller LS, Larson A, Murphy GF, Geha RS (2012) Leukotriene B4-driven neutrophil recruitment to the skin is essential for allergic skin inflammation. Immunity 37(4):747–758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Papayannopoulos V, Metzler KD, Hakkim A, Zychlinsky A (2010) Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps. J Cell Biol 191(3):677–691

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Park K-H, Kurokawa K, Zheng L, Jung D-J, Tateishi K, Jin J-O, Ha N-C, Kang HJ, Matsushita M, Kwak J-Y, Takahashi K, Lee BL (2010) Human serum mannose-binding lectin senses wall teichoic acid glycopolymer of Staphylococcus aureus, which is restricted in infancy. J Biol Chem 285(35):27167–27175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Perera GK, Di Meglio P, Nestle FO (2012) Psoriasis. Annu Rev Pathol 7:385–422

    Article  CAS  PubMed  Google Scholar 

  96. Phillipson M, Kubes P (2011) The neutrophil in vascular inflammation. Nat Med 17(11):1381–1390

    Article  CAS  PubMed  Google Scholar 

  97. Picard C, Puel A, Bonnet M, Ku CL, Bustamante J, Yang K, Soudais C, Dupuis S, Feinberg J, Fieschi C, Elbim C, Hitchcock R, Lammas D, Davies G, Al-Ghonaium A, Al-Rayes H, Al-Jumaah S, Al-Hajjar S, Al-Mohsen IZ, Frayha HH, Rucker R, Hawn TR, Aderem A, Tufenkeji H, Haraguchi S, Day NK, Good RA, Gougerot-Pocidalo MA, Ozinsky A, Casanova JL (2003) Pyogenic bacterial infections in humans with IRAK-4 deficiency. Science 299(5615):2076–2079

    Article  CAS  PubMed  Google Scholar 

  98. Pilsczek FH, Salina D, Poon KKH, Fahey C, Yipp BG, Sibley CD, Robbins SM, Green FHY, Surette MG, Sugai M, Bowden MG, Hussain M, Zhang K, Kubes P (2010) A novel mechanism of rapid nuclear neutrophil extracellular trap formation in response to Staphylococcus aureus. J Immunol 185(12):7413–7425

    Article  CAS  PubMed  Google Scholar 

  99. Pollock JD, Williams DA, Gifford MA, Li LL, Du X, Fisherman J, Orkin SH, Doerschuk CM, Dinauer MC (1995) Mouse model of X-linked chronic granulomatous disease, an inherited defect in phagocyte superoxide production. Nat Genet 9(2):202–209

    Article  CAS  PubMed  Google Scholar 

  100. Proebstl D, Voisin M-B, Woodfin A, Whiteford J, D’Acquisto F, Jones GE, Rowe D, Nourshargh S (2012) Pericytes support neutrophil subendothelial cell crawling and breaching of venular walls in vivo. J Exp Med 209(6):1219–1234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Puel A, Cypowyj S, Bustamante J, Wright JF, Liu L, Lim HK, Migaud M, Israel L, Chrabieh M, Audry M, Gumbleton M, Toulon A, Bodemer C, El-Baghdadi J, Whitters M, Paradis T, Brooks J, Collins M, Wolfman NM, Al-Muhsen S, Galicchio M, Abel L, Picard C, Casanova JL (2011) Chronic mucocutaneous candidiasis in humans with inborn errors of interleukin-17 immunity. Science 332(6025):65–68

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Rankin SM (2010) The bone marrow: a site of neutrophil clearance. J Leukoc Biol 88(2):241–251

    Article  CAS  PubMed  Google Scholar 

  103. Ravetch JV, Kinet J-P (1991) Fc receptors. Annu Rev Immunol 9(1):457–492

    Article  CAS  PubMed  Google Scholar 

  104. Rubin-Bejerano I, Abeijon C, Magnelli P, Grisafi P, Fink GR (2007) Phagocytosis by human neutrophils is stimulated by a unique fungal cell wall component. Cell Host Microbe 2(1):55–67

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Ruocco E, Sangiuliano S, Gravina AG, Miranda A, Nicoletti G (2009) Pyoderma gangrenosum: an updated review. J Eur Acad Dermatol Venereol 23(9):1008–1017

    Article  CAS  PubMed  Google Scholar 

  106. Sadik CD, Kim ND, Luster AD (2011) Neutrophils cascading their way to inflammation. Trends Immunol 32(10):452–460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Scapini P, Lapinet-Vera JA, Gasperini S, Calzetti F, Bazzoni F, Cassatella MA (2000) The neutrophil as a cellular source of chemokines. Immunol Rev 177:195–203

    Article  CAS  PubMed  Google Scholar 

  108. Schwarzenberger P, Huang W, Ye P, Oliver P, Manuel M, Zhang Z, Bagby G, Nelson S, Kolls JK (2000) Requirement of endogenous stem cell factor and granulocyte-colony-stimulating factor for IL-17-mediated granulopoiesis. J Immunol 164(9):4783–4789

    Article  CAS  PubMed  Google Scholar 

  109. Semerad CL, Liu F, Gregory AD, Stumpf K, Link DC (2002) G-CSF is an essential regulator of neutrophil trafficking from the bone marrow to the blood. Immunity 17(4):413–423

    Article  CAS  PubMed  Google Scholar 

  110. Sengelov H, Kjeldsen L, Borregaard N (1993) Control of exocytosis in early neutrophil activation. J Immunol 150(4):1535–1543

    CAS  PubMed  Google Scholar 

  111. Serhan CN (2010) Novel lipid mediators and resolution mechanisms in acute inflammation: to resolve or not? Am J Pathol 177(4):1576–1591

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Shimada T, Park BG, Wolf AJ, Brikos C, Goodridge HS, Becker CA, Reyes CN, Miao EA, Aderem A, Götz F, Liu GY, Underhill DM (2010) Staphylococcus aureus evades lysozyme-based peptidoglycan digestion that links phagocytosis, inflammasome activation, and IL-1beta secretion. Cell Host Microbe 7(1):38–49

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Sims JE, Smith DE (2010) The IL-1 family: regulators of immunity. Nat Rev Immunol 10(2):89–102

    Article  CAS  PubMed  Google Scholar 

  114. Soehnlein O, Lindbom L (2009) Neutrophil-derived azurocidin alarms the immune system. J Leukoc Biol 85(3):344–351

    Article  CAS  PubMed  Google Scholar 

  115. Soehnlein O, Lindbom L (2010) Phagocyte partnership during the onset and resolution of inflammation. Nat Rev Immunol 10(6):427–439

    Article  CAS  PubMed  Google Scholar 

  116. Soehnlein O, Weber C, Lindbom L (2009) Neutrophil granule proteins tune monocytic cell function. Trends Immunol 30(11):538–546

    Article  CAS  PubMed  Google Scholar 

  117. Soehnlein O, Zernecke A, Eriksson EE, Rothfuchs AG, Pham CT, Herwald H, Bidzhekov K, Rottenberg ME, Weber C, Lindbom L (2008) Neutrophil secretion products pave the way for inflammatory monocytes. Blood 112(4):1461–1471

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Stark K, Eckart A, Haidari S, Tirniceriu A, Lorenz M, von Bruhl ML, Gartner F, Khandoga AG, Legate KR, Pless R, Hepper I, Lauber K, Walzog B, Massberg S (2013) Capillary and arteriolar pericytes attract innate leukocytes exiting through venules and ‘instruct’ them with pattern-recognition and motility programs. Nat Immunol 14(1):41–51

    Article  CAS  PubMed  Google Scholar 

  119. Stark MA, Huo Y, Burcin TL, Morris MA, Olson TS, Ley K (2005) Phagocytosis of apoptotic neutrophils regulates granulopoiesis via IL-23 and IL-17. Immunity 22(3):285–294

    Article  CAS  PubMed  Google Scholar 

  120. Sugiyama T, Kohara H, Noda M, Nagasawa T (2006) Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity 25(6):977–988

    Article  CAS  PubMed  Google Scholar 

  121. Sumaria N, Roediger B, Ng LG, Qin J, Pinto R, Cavanagh LL, Shklovskaya E, Fazekas de St Groth B, Triccas JA, Weninger W (2011) Cutaneous immunosurveillance by self-renewing dermal gammadelta T cells. J Exp Med 208(3):505–518

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Suratt BT, Petty JM, Young SK, Malcolm KC, Lieber JG, Nick JA, Gonzalo JA, Henson PM, Worthen GS (2004) Role of the CXCR4/SDF-1 chemokine axis in circulating neutrophil homeostasis. Blood 104(2):565–571

    Article  CAS  PubMed  Google Scholar 

  123. Sweeney CM, Tobin AM, Kirby B (2011) Innate immunity in the pathogenesis of psoriasis. Arch Dermatol Res 303(10):691–705

    Article  CAS  PubMed  Google Scholar 

  124. Tkalcevic J, Novelli M, Phylactides M, Iredale JP, Segal AW, Jr R (2000) Impaired immunity and enhanced resistance to endotoxin in the absence of neutrophil elastase and cathepsin G. Immunity 12(2):201–210

    Article  CAS  PubMed  Google Scholar 

  125. Turner J, Cho Y, Dinh N-N, Waring AJ, Lehrer RI (1998) Activities of LL-37, a cathelin-associated antimicrobial peptide of human neutrophils. Antimicrob Agents Chemother 42(9):2206–2214

    CAS  PubMed  PubMed Central  Google Scholar 

  126. van de Veerdonk FL, Plantinga TS, Hoischen A, Smeekens SP, Joosten LA, Gilissen C, Arts P, Rosentul DC, Carmichael AJ, Smits-van der Graaf CA, Kullberg BJ, van der Meer JW, Lilic D, Veltman JA, Netea MG (2011) STAT1 mutations in autosomal dominant chronic mucocutaneous candidiasis. N Engl J Med 365(1):54–61

    Article  PubMed  Google Scholar 

  127. van der Veen BS, de Winther MP, Heeringa P (2009) Myeloperoxidase: molecular mechanisms of action and their relevance to human health and disease. Antioxid Redox Signal 11(11):2899–2937

    Article  PubMed  CAS  Google Scholar 

  128. Voisin MB, Probstl D, Nourshargh S (2010) Venular basement membranes ubiquitously express matrix protein low-expression regions: characterization in multiple tissues and remodeling during inflammation. Am J Pathol 176(1):482–495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. von Bernuth H, Picard C, Jin Z, Pankla R, Xiao H, Ku CL, Chrabieh M, Mustapha IB, Ghandil P, Camcioglu Y, Vasconcelos J, Sirvent N, Guedes M, Vitor AB, Herrero-Mata MJ, Arostegui JI, Rodrigo C, Alsina L, Ruiz-Ortiz E, Juan M, Fortuny C, Yague J, Anton J, Pascal M, Chang HH, Janniere L, Rose Y, Garty BZ, Chapel H, Issekutz A, Marodi L, Rodriguez-Gallego C, Banchereau J, Abel L, Li X, Chaussabel D, Puel A, Casanova JL (2008) Pyogenic bacterial infections in humans with MyD88 deficiency. Science 321(5889):691–696

    Article  CAS  Google Scholar 

  130. von Vietinghoff S, Ley K (2009) IL-17A controls IL-17F production and maintains blood neutrophil counts in mice. J Immunol 183(2):865–873

    Article  CAS  Google Scholar 

  131. Wang S, Voisin MB, Larbi KY, Dangerfield J, Scheiermann C, Tran M, Maxwell PH, Sorokin L, Nourshargh S (2006) Venular basement membranes contain specific matrix protein low expression regions that act as exit points for emigrating neutrophils. J Exp Med 203(6):1519–1532

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Weinrauch Y, Drujan D, Shapiro SD, Weiss J, Zychlinsky A (2002) Neutrophil elastase targets virulence factors of enterobacteria. Nature 417(6884):91–94

    Article  CAS  PubMed  Google Scholar 

  133. Wengner AM, Pitchford SC, Furze RC, Rankin SM (2008) The coordinated action of G-CSF and ELR + CXC chemokines in neutrophil mobilization during acute inflammation. Blood 111(1):42–49

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Winterbourn CC, Kettle AJ (2013) Redox reactions and microbial killing in the neutrophil phagosome. Antioxid Redox Signal 18(6):642–660

    Article  CAS  PubMed  Google Scholar 

  135. Yamada M, Kubo H, Kobayashi S, Ishizawa K, He M, Suzuki T, Fujino N, Kunishima H, Hatta M, Nishimaki K, Aoyagi T, Tokuda K, Kitagawa M, Yano H, Tamamura H, Fujii N, Kaku M (2011) The increase in surface CXCR4 expression on lung extravascular neutrophils and its effects on neutrophils during endotoxin-induced lung injury. Cell Mol Immunol 8(4):305–314

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Yang CW, Strong BS, Miller MJ, Unanue ER (2010) Neutrophils influence the level of antigen presentation during the immune response to protein antigens in adjuvants. J Immunol 185(5):2927–2934

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Yipp BG, Kubes P (2013) NETosis: how vital is it? Blood 122(16):2784–2794

    Article  CAS  PubMed  Google Scholar 

  138. Yipp BG, Petri B, Salina D, Jenne CN, Scott BN, Zbytnuik LD, Pittman K, Asaduzzaman M, Wu K, Meijndert HC, Malawista SE, de Boisfleury CA, Zhang K, Conly J, Kubes P (2012) Infection-induced NETosis is a dynamic process involving neutrophil multitasking in vivo. Nat Med 18(9):1386–1393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Yousefi S, Mihalache C, Kozlowski E, Schmid I, Simon HU (2009) Viable neutrophils release mitochondrial DNA to form neutrophil extracellular traps. Cell Death Differ 16(11):1438–1444

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank Drs Maté Biro and Shweta Tikoo for their critical reading and inputs on the paper. This work was supported by grants from the NHMRC and the ARC. WW is a fellow of the Cancer Institute New South Wales.

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Authors and Affiliations

  1. The Centenary Institute, Newtown, NSW, 2042, Australia

    Rohit Jain, Andrew J. Mitchell, Szun S. Tay, Ben Roediger & Wolfgang Weninger

  2. Discipline of Dermatology, Sydney Medical School, Sydney, 2006, NSW, Australia

    Wolfgang Weninger

  3. Department of Dermatology, Royal Prince Alfred Hospital, Camperdown, 2050, NSW, Australia

    Wolfgang Weninger

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  1. Rohit Jain
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Correspondence to Wolfgang Weninger .

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  1. Department of Dermatology, Kyoto University Grad Sch of Med., Sakyo-ku, Kyoto, Japan

    Kenji Kabashima

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Jain, R., Mitchell, A.J., Tay, S.S., Roediger, B., Weninger, W. (2016). Neutrophils. In: Kabashima, K. (eds) Immunology of the Skin. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55855-2_9

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