Mobile Innate Immune Cells

  • Walter Gottlieb Land


This chapter describes the broad variety of mobile cells of the innate immune system. The cells include phagocytic cells such as monocytes/macrophages, polymorphonuclear neutrophils, and dendritic cells; cells that release inflammatory mediators such as eosinophils, basophils, and mast cells; and innate lymphoid cells such as natural killer cells as well as unconventional “non-classical” T cells with partial innate function such as natural killer T cells, mucosal-associated invariant T cells, and gammadelta T cells. These mobile innate immune cells represent the core of the immune defense system on the level of those professional cells which operate at the initial phase of infective and sterile tissue injury. Many of these cells are grouped into several subsets. Typically, these cells execute different defense functions such as phagocytic capabilities of phagocytes and killing properties of natural killer cells and unconventional T cells, all properties aimed at getting rid of inciting insults and restoring homeostasis. Another striking feature of these mobile innate immune cells is their role in preparing a robust adaptive immune response upon the presence of nonself or altered-self antigens. In this regard, one can even notice some overlapping functions between innate and adaptive immune cells. Finally, the mobile cells are also involved in the integration of the sessile cells of the innate immune system to combat injury commonly.


  1. 1.
    Kay AB. Paul Ehrlich and the early history of granulocytes. Microbiol Spectr. 2016;4 Available from:
  2. 2.
    Zhang L, Wang C-C. Inflammatory response of macrophages in infection. Hepatobiliary Pancreat Dis Int. 2014;13:138–52. Available from: Scholar
  3. 3.
    Bloom BR, Modlin RL. Mechanisms of defense against intracellular pathogens mediated by human macrophages. Microbiol Spectr. 2016;4 Available from:
  4. 4.
    Robinson JM. Reactive oxygen species in phagocytic leukocytes. Histochem Cell Biol. 2008;130:281–97. Available from: Scholar
  5. 5.
    Segal AW. The function of the NADPH oxidase of phagocytes and its relationship to other NOXs in plants, invertebrates, and mammals. Int J Biochem Cell Biol. 2008;40:604–18. Available from: Scholar
  6. 6.
    Teng T-S, Ji A-L, Ji X-Y, Li Y-Z. Neutrophils and immunity: from bactericidal action to being conquered. J Immunol Res. 2017;2017:9671604. Available from: Scholar
  7. 7.
    Gordon S. Phagocytosis: an immunobiologic process. Immunity. 2016;44:463–75. Available from: Scholar
  8. 8.
    Urb M, Sheppard DC. The role of mast cells in the defence against pathogens. Heitman J, editor. PLoS Pathog. 2012;8:e1002619. Available from: Scholar
  9. 9.
    Hashimoto D, Chow A, Noizat C, Teo P, Beasley MB, Leboeuf M, et al. Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes. Immunity. 2013;38:792–804. Available from: Scholar
  10. 10.
    Wynn TA, Vannella KM. Macrophages in tissue repair, regeneration, and fibrosis. Immunity. 2016;44:450–62. Available from: Scholar
  11. 11.
    Epelman S, Lavine KJ, Randolph GJ. Origin and functions of tissue macrophages. Immunity. 2014;41:21–35. Available from: Scholar
  12. 12.
    Kierdorf K, Prinz M, Geissmann F, Gomez Perdiguero E. Development and function of tissue resident macrophages in mice. Semin Immunol. 2015;27:369–78. Available from: Scholar
  13. 13.
    Robbins CS, Swirski FK. The multiple roles of monocyte subsets in steady state and inflammation. Cell Mol Life Sci. 2010;67:2685–93. Available from: Scholar
  14. 14.
    Davies LC, Jenkins SJ, Allen JE, Taylor PR. Tissue-resident macrophages. Nat Immunol. 2013;14:986–95. Available from: Scholar
  15. 15.
    Gordon S. The macrophage: past, present and future. Eur J Immunol. 2007;37(Suppl 1):S9–17. Available from: Scholar
  16. 16.
    Wynn TA, Chawla A, Pollard JW. Macrophage biology in development, homeostasis and disease. Nature. 2013;496:445–55. Available from: Scholar
  17. 17.
    Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW, Goerdt S, et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity. 2014;41:14–20. Available from: Scholar
  18. 18.
    Gordon S, Taylor PR. Monocyte and macrophage heterogeneity. Nat Rev Immunol. 2005;5:953–64. Available from: Scholar
  19. 19.
    Lawrence T, Natoli G. Transcriptional regulation of macrophage polarization: enabling diversity with identity. Nat Rev Immunol. 2011;11:750–61. Available from: Scholar
  20. 20.
    Mills CD, Kincaid K, Alt JM, Heilman MJ, Hill AM. M-1/M-2 macrophages and the Th1/Th2 paradigm. J Immunol. 2000;164:6166–73. Available from: Scholar
  21. 21.
    Mills CD. M1 and M2 macrophages: oracles of health and disease. Crit Rev Immunol. 2012;32:463–88. Available from: Scholar
  22. 22.
    Murray PJ, Wynn TA. Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol. 2011;11:723–37. Available from: Scholar
  23. 23.
    Yu X, Guo C, Fisher PB, Subjeck JR, Wang X-Y. Scavenger receptors: emerging roles in cancer biology and immunology. Adv Cancer Res. 2015;128:309–64. Available from: Scholar
  24. 24.
    Taylor PR, Martinez-Pomares L, Stacey M, Lin H-H, Brown GD, Gordon S. Macrophage receptors and immune recognition. Annu Rev Immunol. 2005;23:901–44. Available from: Scholar
  25. 25.
    McCoy CE, O’Neill LAJ. The role of toll-like receptors in macrophages. Front Biosci. 2008;13:62–70. Available from: Scholar
  26. 26.
    Elinav E, Strowig T, Henao-Mejia J, Flavell RA. Regulation of the antimicrobial response by NLR proteins. Immunity. 2011;34:665–79. Available from: Scholar
  27. 27.
    Kawai T, Akira S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity. 2011;34:637–50. Available from: Scholar
  28. 28.
    Osorio F, Reis e Sousa C. Myeloid C-type lectin receptors in pathogen recognition and host defense. Immunity. 2011;34:651–64. Available from: Scholar
  29. 29.
    Odegaard JI, Ricardo-Gonzalez RR, Goforth MH, Morel CR, Subramanian V, Mukundan L, et al. Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance. Nature. 2007;447:1116–20. Available from: Scholar
  30. 30.
    Glass CK, Natoli G. Molecular control of activation and priming in macrophages. Nat Immunol. 2016;17:26–33. Available from: Scholar
  31. 31.
    Martinez FO, Helming L, Gordon S. Alternative activation of macrophages: an immunologic functional perspective. Annu Rev Immunol. 2009;27:451–83. Available from: Scholar
  32. 32.
    Meng X-M, Tang PM-K, Li J, Lan HY. Macrophage phenotype in kidney injury and repair. Kidney Dis (Basel, Switzerland). 2015;1:138–46. Available from: Scholar
  33. 33.
    Van Dyken SJ, Locksley RM. Interleukin-4- and interleukin-13-mediated alternatively activated macrophages: roles in homeostasis and disease. Annu Rev Immunol. 2013;31:317–43. Available from: Scholar
  34. 34.
    Geering B, Stoeckle C, Conus S, Simon H-U. Living and dying for inflammation: neutrophils, eosinophils, basophils. Trends Immunol. 2013;34:398–409. Available from: Scholar
  35. 35.
    Scapini P, Marini O, Tecchio C, Cassatella MA. Human neutrophils in the saga of cellular heterogeneity: insights and open questions. Immunol Rev. 2016;273:48–60. Available from: Scholar
  36. 36.
    Mayadas TN, Cullere X, Lowell CA. The multifaceted functions of neutrophils. Annu Rev Pathol. 2014;9:181–218. Available from: Scholar
  37. 37.
    Amulic B, Cazalet C, Hayes GL, Metzler KD, Zychlinsky A. Neutrophil function: from mechanisms to disease. Annu Rev Immunol. 2012;30:459–89. Available from: Scholar
  38. 38.
    Desai J, Mulay SR, Nakazawa D, Anders H-J. Matters of life and death. How neutrophils die or survive along NET release and is “NETosis” = necroptosis? Cell Mol Life Sci. 2016;73:2211–9. Available from: Scholar
  39. 39.
    Scapini P, Lapinet-Vera JA, Gasperini S, Calzetti F, Bazzoni F, Cassatella MA. The neutrophil as a cellular source of chemokines. Immunol Rev. 2000;177:195–203. Available from: Scholar
  40. 40.
    Futosi K, Fodor S, Mócsai A. Neutrophil cell surface receptors and their intracellular signal transduction pathways. Int Immunopharmacol. 2013;17:638–50. Available from: Scholar
  41. 41.
    de Oliveira S, Rosowski EE, Huttenlocher A. Neutrophil migration in infection and wound repair: going forward in reverse. Nat Rev Immunol. 2016;16:378–91. Available from: Scholar
  42. 42.
    Li X, Utomo A, Cullere X, Choi MM, Milner DA, Venkatesh D, et al. 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. 2011;10:603–15. Available from: Scholar
  43. 43.
    Trinchieri G, Sher A. Cooperation of Toll-like receptor signals in innate immune defence. Nat Rev Immunol. 2007;7:179–90. Available from: Scholar
  44. 44.
    Kanneganti T-D, Lamkanfi M, Núñez G. Intracellular NOD-like receptors in host defense and disease. Immunity. 2007;27:549–59. Available from: Scholar
  45. 45.
    Kolli D, Velayutham TS, Casola A. Host-viral interactions: role of pattern recognition receptors (PRRs) in human pneumovirus infections. Pathogens. 2013;2:2. Available from: Scholar
  46. 46.
    Sundd P, Pospieszalska MK, Ley K. Neutrophil rolling at high shear: flattening, catch bond behavior, tethers and slings. Mol Immunol. 2013;55:59–69. Available from: Scholar
  47. 47.
    Brinkmann V, Zychlinsky A. Neutrophil extracellular traps: is immunity the second function of chromatin? J Cell Biol. 2012;198:773–83. Available from: Scholar
  48. 48.
    Dąbrowska D, Jabłońska E, Garley M, Ratajczak-Wrona W, Iwaniuk A. New aspects of the biology of neutrophil extracellular traps. Scand J Immunol. 2016;84:317. Available from: Scholar
  49. 49.
    Yang H, Biermann MH, Brauner JM, Liu Y, Zhao Y, Herrmann M. New insights into neutrophil extracellular traps: mechanisms of formation and role in inflammation. Front Immunol. 2016;7:302. Available from: Scholar
  50. 50.
    Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, et al. Neutrophil extracellular traps kill bacteria. Science. 2004;303:1532–5. Available from: Scholar
  51. 51.
    Metzler KD, Goosmann C, Lubojemska A, Zychlinsky A, Papayannopoulos V. A myeloperoxidase-containing complex regulates neutrophil elastase release and actin dynamics during NETosis. Cell Rep. 2014;8:883–96. Available from: Scholar
  52. 52.
    Fuchs TA, 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;176:231–41. Available from: Scholar
  53. 53.
    Iba T, Hashiguchi N, Nagaoka I, Tabe Y, Murai M. Neutrophil cell death in response to infection and its relation to coagulation. J Intens Care. 2013;1:13. Available from: Scholar
  54. 54.
    Leliefeld PHC, Wessels CM, Leenen LPH, Koenderman L, Pillay J. The role of neutrophils in immune dysfunction during severe inflammation. Crit Care. 2016;20:73. Available from: Scholar
  55. 55.
    Ehrlich P. Beitrage zur Kenntnis der granulierten Bindegewebszellen und der eosinophilen Leukocyten. Arch Anat Physiol. 1879;3:166. Available from:äge+zur+Kenntnis+der+granulierten+Bindegewebszellen+und+der+eosinophilen+Leukocythen.&publication_year=1879&pages=166-169.Google Scholar
  56. 56.
    Schadewaldt H. Paul Ehrlich und die Faszination der Farben. Chemother. J. 2004;13:41–5. Available from: Scholar
  57. 57.
    Hogan SP, Rosenberg HF, Moqbel R, Phipps S, Foster PS, Lacy P, et al. Eosinophils: biological properties and role in health and disease. Clin Exp Allergy. 2008;38:709–50. Available from: Scholar
  58. 58.
    Long H, Liao W, Wang L, Lu Q. A player and coordinator: the versatile roles of eosinophils in the immune system. Transfus Med Hemother. 2016;43:96–108. Available from: Scholar
  59. 59.
    Shamri R, Xenakis JJ, Spencer LA. Eosinophils in innate immunity: an evolving story. Cell Tissue Res. 2011;343:57–83. Available from: Scholar
  60. 60.
    Kvarnhammar AM, Cardell LO. Pattern-recognition receptors in human eosinophils. Immunology. 2012;136:11–20. Available from: Scholar
  61. 61.
    Driss V, Legrand F, Hermann E, Loiseau S, Guerardel Y, Kremer L, et al. TLR2-dependent eosinophil interactions with mycobacteria: role of alpha-defensins. Blood. 2009;113:3235–44. Available from: Scholar
  62. 62.
    Lotfi R, Herzog GI, DeMarco RA, Beer-Stolz D, Lee JJ, Rubartelli A, et al. Eosinophils oxidize damage-associated molecular pattern molecules derived from stressed cells. J Immunol. 2009;183:5023–31. Available from: Scholar
  63. 63.
    Kobayashi T, Kouzaki H, Kita H. Human eosinophils recognize endogenous danger signal crystalline uric acid and produce proinflammatory cytokines mediated by autocrine ATP. J Immunol. 2010;184:6350–8. Available from: Scholar
  64. 64.
    Acharya KR, Ackerman SJ. Eosinophil granule proteins: form and function. J Biol Chem. 2014;289:17406–15. Available from: Scholar
  65. 65.
    Marone G, Borriello F, Varricchi G, Genovese A, Granata F. Basophils: historical reflections and perspectives. Chem Immunol Allergy. 2014;100:172–92. Available from: Scholar
  66. 66.
    Oetjen LK, Noti M, Kim BS. New insights into basophil heterogeneity. Semin Immunopathol. 2016;38:549–61. Available from: Scholar
  67. 67.
    Lundberg K, Rydnert F, Broos S, Andersson M, Greiff L, Lindstedt M. C-type lectin receptor expression on human basophils and effects of allergen-specific immunotherapy. Scand J Immunol. 2016;84:150–7. Available from: Scholar
  68. 68.
    Suurmond J, Stoop JN, Rivellese F, Bakker AM, Huizinga TWJ, Toes REM. Activation of human basophils by combined toll-like receptor- and FcεRI-triggering can promote Th2 skewing of naive T helper cells. Eur J Immunol. 2014;44:386–96. Available from: Scholar
  69. 69.
    Schwartz C, Eberle JU, Voehringer D. Basophils in inflammation. Eur J Pharmacol. 2016;778:90–5. Available from: Scholar
  70. 70.
    Marone G, Varricchi G, Loffredo S, Galdiero MR, Rivellese F, de Paulis A. Are basophils and mast cells masters in HIV infection? Int Arch Allergy Immunol. 2016;171:158–65. Available from: Scholar
  71. 71.
    Miyake K, Karasuyama H. Emerging roles of basophils in allergic inflammation. Allergol Int. 2017;66:382. Available from: Scholar
  72. 72.
    Okayama Y, Kawakami T. Development, migration, and survival of mast cells. Immunol Res. 2006;34:97–115. Available from: Scholar
  73. 73.
    Abraham SN, St John AL. Mast cell-orchestrated immunity to pathogens. Nat Rev Immunol. 2010;10:440–52. Available from: Scholar
  74. 74.
    Singh J, Shah R, Singh D. Targeting mast cells: uncovering prolific therapeutic role in myriad diseases. Int Immunopharmacol. 2016;40:362–84. Available from: Scholar
  75. 75.
    DeBruin EJ, Gold M, Lo BC, Snyder K, Cait A, Lasic N, et al. Mast cells in human health and disease. Methods Mol. Biol. 2015;1220:93–119. Available from: Scholar
  76. 76.
    Morita H, Saito H, Matsumoto K, Nakae S. Regulatory roles of mast cells in immune responses. Semin Immunopathol. 2016;38:623–9. Available from: Scholar
  77. 77.
    Arthur G, Bradding P. New developments in mast cell biology: clinical implications. Chest. 2016;150:680–93. Available from: Scholar
  78. 78.
    Krystel-Whittemore M, Dileepan KN, Wood JG. Mast cell: a multi-functional master cell. Front Immunol. 2015;6:620. Available from: Scholar
  79. 79.
    Irani AA, Schechter NM, Craig SS, DeBlois G, Schwartz LB. Two types of human mast cells that have distinct neutral protease compositions. Proc Natl Acad Sci U S A. 1986;83:4464–8. Available from: Scholar
  80. 80.
    Sandig H, Bulfone-Paus S. TLR signaling in mast cells: common and unique features. Front Immunol. 2012;3:185. Available from: Scholar
  81. 81.
    Graham AC, Hilmer KM, Zickovich JM, Obar JJ. Inflammatory response of mast cells during influenza A virus infection is mediated by active infection and RIG-I signaling. J Immunol. 2013;190:4676–84. Available from: Scholar
  82. 82.
    Bax HJ, Keeble AH, Gould HJ. Cytokinergic IgE action in mast cell activation. Front Immunol. 2012;3:229. Available from: Scholar
  83. 83.
    Dema B, Suzuki R, Rivera J. Rethinking the role of immunoglobulin E and its high-affinity receptor: new insights into allergy and beyond. Int Arch Allergy Immunol. 2014;164:271–9. Available from: Scholar
  84. 84.
    Qiao H, Andrade MV, Lisboa FA, Morgan K, Beaven MA. FcepsilonR1 and toll-like receptors mediate synergistic signals to markedly augment production of inflammatory cytokines in murine mast cells. Blood. 2006;107:610–8. Available from: Scholar
  85. 85.
    Sibilano R, Frossi B, Pucillo CE. Mast cell activation: a complex interplay of positive and negative signaling pathways. Eur J Immunol. 2014;44:2558–66. Available from: Scholar
  86. 86.
    Jin M, Yu B, Zhang W, Zhang W, Xiao Z, Mao Z, et al. Toll-like receptor 2-mediated MAPKs and NF-κB activation requires the GNAO1-dependent pathway in human mast cells. Integr Biol (Camb). 2016;8:968–75. Available from: Scholar
  87. 87.
    Williams CM, Galli SJ. The diverse potential effector and immunoregulatory roles of mast cells in allergic disease. J Allergy Clin Immunol. 2000;105:847–59. Available from: Scholar
  88. 88.
    Agier J, Brzezińska-Błaszczyk E. Cathelicidins and defensins regulate mast cell antimicrobial activity. Postȩpy Hig i Med doświadczalnej. 2016;70:618–36. Available from: Scholar
  89. 89.
    Enoksson M, Lyberg K, Möller-Westerberg C, Fallon PG, Nilsson G, Lunderius-Andersson C. Mast cells as sensors of cell injury through IL-33 recognition. J Immunol. 2011;186:2523–8. Available from: Scholar
  90. 90.
    Suurmond J, Dorjée AL, Knol EF, Huizinga TWJ, Toes REM. Differential TLR-induced cytokine production by human mast cells is amplified by FcɛRI triggering. Clin Exp Allergy. 2015;45:788–96. Available from: Scholar
  91. 91.
    Theoharides TC, Alysandratos K-D, Angelidou A, Delivanis D-A, Sismanopoulos N, Zhang B, et al. Mast cells and inflammation. Biochim Biophys Acta. 2012;1822:21–33. Available from: Scholar
  92. 92.
    Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9:654–9. Available from: Scholar
  93. 93.
    Li F, Wang Y, Lin L, Wang J, Xiao H, Li J, et al. Mast cell-derived exosomes promote Th2 cell differentiation via OX40L-OX40 ligation. J Immunol Res. 2016;2016:3623898. Available from: Scholar
  94. 94.
    Möllerherm H, von Köckritz-Blickwede M, Branitzki-Heinemann K. Antimicrobial activity of mast cells: role and relevance of extracellular DNA traps. Front Immunol. 2016;7:265. Available from: Scholar
  95. 95.
    Metz M, Grimbaldeston MA, Nakae S, Piliponsky AM, Tsai M, Galli SJ. Mast cells in the promotion and limitation of chronic inflammation. Immunol Rev. 2007;217:304–28. Available from: Scholar
  96. 96.
    Virk H, Arthur G, Bradding P. Mast cells and their activation in lung disease. Transl Res. 2016;174:60–76. Available from: Scholar
  97. 97.
    Steinman RM, Cohn ZA. Pillars article: identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J. Exp. Med.1973. 137: 1142–1162. J Immunol. 2007;178:5–25. Available from: Scholar
  98. 98.
    Steinman RM. Decisions about dendritic cells: past, present, and future. Annu Rev Immunol. 2012;30:1–22. Available from: Scholar
  99. 99.
    Steinman RM, Hemmi H. Dendritic cells: translating innate to adaptive immunity. Curr Top Microbiol Immunol. 2006;311:17–58. Available from: Scholar
  100. 100.
    Shortman K, Liu Y-J. Mouse and human dendritic cell subtypes. Nat Rev Immunol. 2002;2:151–61. Available from: Scholar
  101. 101.
    Kushwah R, Hu J. Complexity of dendritic cell subsets and their function in the host immune system. Immunology. 2011;133:409–19. Available from: Scholar
  102. 102.
    Steinman RM, Idoyaga J. Features of the dendritic cell lineage. Immunol Rev. 2010;234:5–17. Available from: Scholar
  103. 103.
    Chen P, Denniston AK, Hirani S, Hannes S, Nussenblatt RB. Role of dendritic cell subsets in immunity and their contribution to noninfectious uveitis. Surv Ophthalmol. 2015;60:242–9. Available from: Scholar
  104. 104.
    Merad M, Sathe P, Helft J, Miller J, Mortha A. The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu Rev Immunol. 2013;31:563–604. Available from: Scholar
  105. 105.
    Villadangos JA, Schnorrer P. Intrinsic and cooperative antigen-presenting functions of dendritic-cell subsets in vivo. Nat Rev Immunol. 2007;7:543–55. Available from: Scholar
  106. 106.
    Segura E, Villadangos JA. Antigen presentation by dendritic cells in vivo. Curr Opin Immunol. 2009;21:105–10. Available from: Scholar
  107. 107.
    Joffre OP, Segura E, Savina A, Amigorena S. Cross-presentation by dendritic cells. Nat Rev Immunol. 2012;12:557–69. Available from: Scholar
  108. 108.
    Förster R, Braun A, Worbs T. Lymph node homing of T cells and dendritic cells via afferent lymphatics. Trends Immunol. 2012;33:271–80. Available from: Scholar
  109. 109.
    Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature. 1998;392:245–52. Available from: Scholar
  110. 110.
    Durand M, Segura E. The known unknowns of the human dendritic cell network. Front Immunol. 2015;6:129. Available from: Scholar
  111. 111.
    Heesters BA, Myers RC, Carroll MC. Follicular dendritic cells: dynamic antigen libraries. Nat Rev Immunol. 2014;14:495–504. Available from: Scholar
  112. 112.
    Kranich J, Krautler NJ. How follicular dendritic cells shape the B-cell antigenome. Front Immunol. 2016;7:225. Available from: Scholar
  113. 113.
    Dalod M, Chelbi R, Malissen B, Lawrence T. Dendritic cell maturation: functional specialization through signaling specificity and transcriptional programming. EMBO J. 2014;33:1104–16. Available from: Scholar
  114. 114.
    Cella M, Jarrossay D, Facchetti F, Alebardi O, Nakajima H, Lanzavecchia A, et al. Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon. Nat Med. 1999;5:919–23. Available from: Scholar
  115. 115.
    Nizzoli G, Krietsch J, Weick A, Steinfelder S, Facciotti F, Gruarin P, et al. Human CD1c+ dendritic cells secrete high levels of IL-12 and potently prime cytotoxic T-cell responses. Blood. 2013;122:932–42. Available from: Scholar
  116. 116.
    Spits H, Artis D, Colonna M, Diefenbach A, Di Santo JP, Eberl G, et al. Innate lymphoid cells--a proposal for uniform nomenclature. Nat Rev Immunol. 2013;13:145–9. Available from: Scholar
  117. 117.
    Sonnenberg GF, Mjösberg J, Spits H, Artis D. SnapShot: innate lymphoid cells. Immunity. 2013;39:622–622.e1. Available from: Scholar
  118. 118.
    Walker JA, Barlow JL, McKenzie ANJ. Innate lymphoid cells--how did we miss them? Nat Rev Immunol. 2013;13:75–87. Available from: Scholar
  119. 119.
    Artis D, Spits H. The biology of innate lymphoid cells. Nature. 2015;517:293–301. Available from: Scholar
  120. 120.
    Sonnenberg GF, Artis D. Innate lymphoid cells in the initiation, regulation and resolution of inflammation. Nat Med. 2015;21:698–708. Available from: Scholar
  121. 121.
    Klose CSN, Artis D. Innate lymphoid cells as regulators of immunity, inflammation and tissue homeostasis. Nat Immunol. 2016;17:765–74. Available from: Scholar
  122. 122.
    Lai D-M, Shu Q, Fan J. The origin and role of innate lymphoid cells in the lung. Mil Med Res. 2016;3:25. Available from: Scholar
  123. 123.
    Kiessling R, Klein E, Pross H, Wigzell H. “Natural” killer cells in the mouse. II. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Characteristics of the killer cell. Eur J Immunol. 1975;5:117–21. Available from: Scholar
  124. 124.
    Pross HF, Jondal M. Cytotoxic lymphocytes from normal donors. A functional marker of human non-T lymphocytes. Clin Exp Immunol. 1975;21:226–35. Available from: Scholar
  125. 125.
    Mebius RE, Rennert P, Weissman IL. Developing lymph nodes collect CD4+CD3- LTbeta+ cells that can differentiate to APC, NK cells, and follicular cells but not T or B cells. Immunity. 1997;7:493–504. Available from: Scholar
  126. 126.
    Martinez-Gonzalez I, Mathä L, Steer CA, Takei F. Immunological memory of group 2 innate lymphoid cells. Trends Immunol. 2017;38:423–31. Available from: Scholar
  127. 127.
    Sun JC, Lanier LL. NK cell development, homeostasis and function: parallels with CD8+ T cells. Nat Rev Immunol. 2011;11:645–57. Available from: Scholar
  128. 128.
    Lanier LL. NKG2D receptor and its ligands in host defense. Cancer Immunol Res. 2015;3:575–82. Available from: Scholar
  129. 129.
    Klose CSN, Flach M, Möhle L, Rogell L, Hoyler T, Ebert K, et al. Differentiation of type 1 ILCs from a common progenitor to all helper-like innate lymphoid cell lineages. Cell. 2014;157:340–56. Available from: Scholar
  130. 130.
    Sanati G, Aryan Z, Barbadi M, Rezaei N. Innate lymphoid cells are pivotal actors in allergic, inflammatory and autoimmune diseases. Expert Rev Clin Immunol. 2015;11:885–95. Available from: Scholar
  131. 131.
    Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S. Functions of natural killer cells. Nat Immunol. 2008;9:503–10. Available from: Scholar
  132. 132.
    Mandal A, Viswanathan C. Natural killer cells: in health and disease. Hematol Oncol Stem Cell Ther. 2015;8:47–55. Scholar
  133. 133.
    Moffett A, Colucci F. Uterine NK cells: active regulators at the maternal-fetal interface. J Clin Invest. 2014;124:1872–9. Available from: Scholar
  134. 134.
    Björkström NK, Ljunggren H-G, Michaëlsson J. Emerging insights into natural killer cells in human peripheral tissues. Nat Rev Immunol. 2016;16:310–20. Available from: Scholar
  135. 135.
    Cooper MA, Fehniger TA, Caligiuri MA. The biology of human natural killer-cell subsets. Trends Immunol. 2001;22:633–40. Available from: Scholar
  136. 136.
    Cooper MA, Fehniger TA, Turner SC, Chen KS, Ghaheri BA, Ghayur T, et al. Human natural killer cells: a unique innate immunoregulatory role for the CD56(bright) subset. Blood. 2001;97:3146–51. Available from: Scholar
  137. 137.
    Björkström NK, Riese P, Heuts F, Andersson S, Fauriat C, Ivarsson MA, et al. Expression patterns of NKG2A, KIR, and CD57 define a process of CD56dim NK-cell differentiation uncoupled from NK-cell education. Blood. 2010;116:3853–64. Available from: Scholar
  138. 138.
    Lopez-Vergès S, Milush JM, Pandey S, York VA, Arakawa-Hoyt J, Pircher H, et al. CD57 defines a functionally distinct population of mature NK cells in the human CD56dimCD16+ NK-cell subset. Blood. 2010;116:3865–74. Available from: Scholar
  139. 139.
    Yu J, Mao HC, Wei M, Hughes T, Zhang J, Park I, et al. CD94 surface density identifies a functional intermediary between the CD56bright and CD56dim human NK-cell subsets. Blood. 2010;115:274–81. Available from: Scholar
  140. 140.
    Bryceson YT, Chiang SCC, Darmanin S, Fauriat C, Schlums H, Theorell J, et al. Molecular mechanisms of natural killer cell activation. J Innate Immun. 2011;3:216–26. Available from: Scholar
  141. 141.
    Vilches C, Parham P. KIR: diverse, rapidly evolving receptors of innate and adaptive immunity. Annu Rev Immunol. 2002;20:217–51. Available from: Scholar
  142. 142.
    Ashouri E, Dabbaghmanesh MH, Ranjbar Omrani G. Presence of more activating KIR genes is associated with Hashimoto’s thyroiditis. Endocrine. 2014;46:519–25. Available from: Scholar
  143. 143.
    Popko K, Górska E. The role of natural killer cells in pathogenesis of autoimmune diseases. Cent Eur J Immunol. 2015;4:470–6. Available from: Scholar
  144. 144.
    Ferlazzo G, Morandi B. Cross-talks between natural killer cells and distinct subsets of dendritic cells. Front Immunol. 2014;5:159. Available from: Scholar
  145. 145.
    Ljunggren HG, Kärre K. In search of the “missing self”: MHC molecules and NK cell recognition. Immunol Today. 1990;11:237–44. Available from: Scholar
  146. 146.
    Kim S, Poursine-Laurent J, Truscott SM, Lybarger L, Song Y-J, Yang L, et al. Licensing of natural killer cells by host major histocompatibility complex class I molecules. Nature. 2005;436:709–13. Available from: Scholar
  147. 147.
    Boudreau JE, Liu X-R, Zhao Z, Zhang A, Shultz LD, Greiner DL, et al. Cell-extrinsic MHC class I molecule engagement augments human NK cell education programmed by cell-intrinsic MHC class I. Immunity. 2016;45:280–91. Available from: Scholar
  148. 148.
    Fauriat C, Long EO, Ljunggren H-G, Bryceson YT. Regulation of human NK-cell cytokine and chemokine production by target cell recognition. Blood. 2010;115:2167–76. Available from: Scholar
  149. 149.
    O’Sullivan TE, Sun JC, Lanier LL. Natural killer cell memory. Immunity. 2015;43:634–45. Available from: Scholar
  150. 150.
    Cerwenka A, Lanier LL. Natural killer cell memory in infection, inflammation and cancer. Nat Rev Immunol. 2016;16:112–23. Available from: Scholar
  151. 151.
    Rölle A, Brodin P. Immune adaptation to environmental influence: the case of NK cells and HCMV. Trends Immunol. 2016;37:233–43. Available from: Scholar
  152. 152.
    Baggio L, Laureano ÁM, Silla LM da R, Lee DA. Natural killer cell adoptive immunotherapy: coming of age. Clin Immunol. 2017;117:3. Available from: Scholar
  153. 153.
    Li S, Yang D, Peng T, Wu Y, Tian Z, Ni B. Innate lymphoid cell-derived cytokines in autoimmune diseases. J Autoimmun. 2017;83:62. Available from: Scholar
  154. 154.
    Kronenberg M, Gapin L. The unconventional lifestyle of NKT cells. Nat Rev Immunol. 2002;2:557–68. Available from: Scholar
  155. 155.
    Godfrey DI, Stankovic S, Baxter AG. Raising the NKT cell family. Nat Immunol. 2010;11:197–206. Available from: Scholar
  156. 156.
    Godfrey DI, Uldrich AP, McCluskey J, Rossjohn J, Moody DB. The burgeoning family of unconventional T cells. Nat Immunol. 2015;16:1114–23. Available from: Scholar
  157. 157.
    Dusseaux M, Martin E, Serriari N, Péguillet I, Premel V, Louis D, et al. Human MAIT cells are xenobiotic-resistant, tissue-targeted, CD161hi IL-17-secreting T cells. Blood. 2011;117:1250–9. Available from: Scholar
  158. 158.
    Kurioka A, Walker LJ, Klenerman P, Willberg CB. MAIT cells: new guardians of the liver. Clin Transl Immunol. 2016;5:e98. Available from: Scholar
  159. 159.
    Jiang H, Chess L. The specific regulation of immune responses by CD8+ T cells restricted by the MHC class Ib molecule, Qa-1. Annu Rev Immunol. 2000;18:185–216. Available from: Scholar
  160. 160.
    Anderson CK, Brossay L. The role of MHC class Ib-restricted T cells during infection. Immunogenetics. 2016;68:677–91. Available from: Scholar
  161. 161.
    Malik S, Want MY, Awasthi A. The emerging roles of gamma-delta T cells in tissue inflammation in experimental autoimmune encephalomyelitis. Front Immunol. 2016;7:14. Available from: Scholar
  162. 162.
    Bendelac A, Savage PB, Teyton L. The biology of NKT cells. Annu Rev Immunol. 2007;25:297–336. Available from: Scholar
  163. 163.
    Dasgupta S, Kumar V. Type II NKT cells: a distinct CD1d-restricted immune regulatory NKT cell subset. Immunogenetics. 2016;68:665–76. Available from: Scholar
  164. 164.
    Chan AC, Leeansyah E, Cochrane A, d’Udekem d’Acoz Y, Mittag D, Harrison LC, et al. Ex-vivo analysis of human natural killer T cells demonstrates heterogeneity between tissues and within established CD4(+) and CD4(-) subsets. Clin Exp Immunol. 2013;172:129–37. Available from: Scholar
  165. 165.
    Kain L, Costanzo A, Webb B, Holt M, Bendelac A, Savage PB, et al. Endogenous ligands of natural killer T cells are alpha-linked glycosylceramides. Mol Immunol. 2015;68:94–7. Available from: Scholar
  166. 166.
    Kuylenstierna C, Björkström NK, Andersson SK, Sahlström P, Bosnjak L, Paquin-Proulx D, et al. NKG2D performs two functions in invariant NKT cells: direct TCR-independent activation of NK-like cytolysis and co-stimulation of activation by CD1d. Eur J Immunol. 2011;41:1913–23. Available from: Scholar
  167. 167.
    Kohlgruber AC, Donado CA, LaMarche NM, Brenner MB, Brennan PJ. Activation strategies for invariant natural killer T cells. Immunogenetics. 2016;68:649–63. Available from: Scholar
  168. 168.
    Tatituri RVV, Watts GFM, Bhowruth V, Barton N, Rothchild A, Hsu F-F, et al. Recognition of microbial and mammalian phospholipid antigens by NKT cells with diverse TCRs. Proc Natl Acad Sci U S A. 2013;110:1827–32. Available from: Scholar
  169. 169.
    Treiner E, Duban L, Moura IC, Hansen T, Gilfillan S, Lantz O. Mucosal-associated invariant T (MAIT) cells: an evolutionarily conserved T cell subset. Microbes Infect. 2005;7:552–9. Available from: Scholar
  170. 170.
    Ussher JE, Klenerman P, Willberg CB. Mucosal-associated invariant T-cells: new players in anti-bacterial immunity. Front Immunol. 2014;5:450. Available from: Scholar
  171. 171.
    Wong EB, Ndung’u T, Kasprowicz VO. The role of MAIT cells in infectious diseases. Immunology. 2017;150:45. Available from: Scholar
  172. 172.
    Le Bourhis L, Martin E, Péguillet I, Guihot A, Froux N, Coré M, et al. Antimicrobial activity of mucosal-associated invariant T cells. Nat Immunol. 2010;11:701–8. Available from: Scholar
  173. 173.
    Kjer-Nielsen L, Patel O, Corbett AJ, Le Nours J, Meehan B, Liu L, et al. MR1 presents microbial vitamin B metabolites to MAIT cells. Nature. 2012;491:717–23. Available from: Scholar
  174. 174.
    Gold MC, Cerri S, Smyk-Pearson S, Cansler ME, Vogt TM, Delepine J, et al. Human mucosal-associated invariant T cells detect bacterially infected cells. PLoS Biol. 2010;8:e1000407. Available from: Scholar
  175. 175.
    Georgel P, Radosavljevic M, Macquin C, Bahram S. The non-conventional MHC class I MR1 molecule controls infection by Klebsiella pneumoniae in mice. Mol Immunol. 2011;48:769–75. Available from: Scholar
  176. 176.
    Carding SR, Egan PJ. Gammadelta T cells: functional plasticity and heterogeneity. Nat Rev Immunol. 2002;2:336–45. Available from: Scholar
  177. 177.
    Ribeiro ST, Ribot JC, Silva-Santos B. Five layers of receptor signaling in γδ T-cell differentiation and activation. Front Immunol. 2015;6:15. Available from: Scholar
  178. 178.
    Fay NS, Larson EC, Jameson JM. Chronic inflammation and γδ T cells. Front Immunol. 2016;7:210. Available from: Scholar
  179. 179.
    Lalor SJ, McLoughlin RM. Memory γδ T cells-newly appreciated protagonists in infection and immunity. Trends Immunol. 2016;37:690–702. Available from: Scholar
  180. 180.
    Kabelitz D, Déchanet-Merville J. Recent advances in gamma/delta T cell biology: new ligands, new functions, and new translational perspectives. Front Immunol. 2015;6:371. Available from: Scholar
  181. 181.
    Ribot JC, Debarros A, Silva-Santos B. Searching for “signal 2”: costimulation requirements of γδ T cells. Cell Mol Life Sci. 2011;68:2345–55. Available from: Scholar
  182. 182.
    Correia DV, Lopes A, Silva-Santos B. Tumor cell recognition by γδ T lymphocytes: T-cell receptor vs. NK-cell receptors. Oncoimmunology. 2013;2:e22892. Available from: Scholar
  183. 183.
    Watanabe N, Gavrieli M, Sedy JR, Yang J, Fallarino F, Loftin SK, et al. BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1. Nat Immunol. 2003;4:670–9. Available from: Scholar
  184. 184.
    Tefit JN, Crabé S, Orlandini B, Nell H, Bendelac A, Deng S, et al. Efficacy of ABX196, a new NKT agonist, in prophylactic human vaccination. Vaccine. 2014;32:6138–45. Available from: Scholar
  185. 185.
    Legut M, Cole DK, Sewell AK. The promise of γδ T cells and the γδ T cell receptor for cancer immunotherapy. Cell Mol Immunol. 2015;12:656–68. Available from: Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.University of StrasbourgMolecular ImmunoRheumatology, Laboratory of Excellence TransplantexStrasbourgFrance

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