It’s Only Innate Immunity But I Like it

  • Emanuela Marcenaro
  • Mariella Della Chiesa
  • Alessandra Dondero
  • Bruna Ferranti
  • Alessandro MorettaEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 590)


Natural Killer (NK) cells are capable of discriminating between normal and virus-infected cells or cells undergoing tumor transformation1,2. The selective elimination of abnormal target cells, based on classical NK-mediated cytotoxicity, is the result of the combined function of activating receptors including NCR and NKG2D3,4 and inhibitory receptors such as Killer Ig-like receptors (KIR) and CD94/NKG2A5, 6, 7, 8 on NK cells as well as of the expression of their specific ligands on target cells9, 10, 11.


Dendritic Cell Mast Cell Natural Killer Cell Plasmacytoid Dendritic Cell Human Natural Killer Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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8. References

  1. 1.
    G. Trinchieri. Biology of natural killer cells. Adv Immunol 47:187–376 (1989).PubMedCrossRefGoogle Scholar
  2. 2.
    A. Moretta, C. Bottino, M.C. Mingari, R. Biassoni and L. Moretta. What is a natural killer cell? Nat Immunol 3(1):6–8 (2002).PubMedCrossRefGoogle Scholar
  3. 3.
    A. Moretta, C. Bottino, M. Vitale, D. Pende, C. Cantoni, M.C. Mingari, R. Biassoni and L. Moretta. Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. Annu Rev Immunol 19:197–223 (2001).PubMedCrossRefGoogle Scholar
  4. 4.
    E. Vivier, J.A. Nunes and F. Vely. Natural killer cell signaling pathways. Science 306(5701):1517–1519 (2004).PubMedCrossRefGoogle Scholar
  5. 5.
    A. Moretta, C. Bottino, M. Vitale, D. Pende, R. Biassoni, M.C. Mingari and L. Moretta. Receptors for HLA class-I molecules in human natural killer cells. Annu Rev Immunol 14:619–648 (1996).PubMedCrossRefGoogle Scholar
  6. 6.
    E.O. Long. Regulation of immune responses through inhibitory receptors. Annu Rev Immunol 17:875–904 (1999).PubMedCrossRefGoogle Scholar
  7. 7.
    M. Lopez-Botet, M. Llano, F. Navarro and T. Bellon. NK cell recognition of nonclassical HLA class I molecules. Semin Immunol 12(2):109–119 (2000).PubMedCrossRefGoogle Scholar
  8. 8.
    C. Vilches and P. Parham. KIR: diverse, rapidly evolving receptors of innate and adaptive immunity. Annu Rev Immunol 20:217–251 (2002).PubMedCrossRefGoogle Scholar
  9. 9.
    C. Bottino, R. Castriconi, L. Moretta and A. Moretta. Cellular ligands of activating NK receptors. Trends Immunol 26(4):221–226 (2005).PubMedCrossRefGoogle Scholar
  10. 10.
    A. Cerwenka and L.L. Lanier. Ligands for natural killer cell receptors: redundancy or specificity. Immunol Rev 181:158–169 (2001).PubMedCrossRefGoogle Scholar
  11. 11.
    D.H. Raulet. Roles of the NKG2D immunoreceptor and its ligands. Nat Rev Immunol 3(10):781–790 (2003).PubMedCrossRefGoogle Scholar
  12. 12.
    N.C. Fernandez, A. Lozier, C. Flament, P. Ricciardi-Castagnoli, D. Bellet, M. Suter, M. Perricaudet, T. Tursz, E. Maraskovsky and L. Zitvogel. Dendritic cells directly trigger NK cell functions: cross-talk relevant in innate anti-tumor immune responses in vivo. Nat Med 5(4):405–411 (1999).PubMedCrossRefGoogle Scholar
  13. 13.
    J.L. Wilson, L.C. Heffler, J. Charo, A. Scheynius, M.T. Bejarano and H.G. Ljunggren. Targeting of human dendritic cells by autologous NK cells. J Immunol 163(12):6365–6370 (1999).PubMedGoogle Scholar
  14. 14.
    E. Carbone, G. Terrazzano, G. Ruggiero, D. Zanzi, A. Ottaiano, C. Manzo, K. Karre and S. Zappacosta. Recognition of autologous dendritic cells by human NK cells. Eur J Immunol 29(12):4022–4029 (1999).PubMedCrossRefGoogle Scholar
  15. 15.
    G. Ferlazzo, M.L. Tsang, L. Moretta, G. Melioli, R. M Steinman and C. Munz. Human dendritic cells activate resting natural killer (NK) cells and are recognized via the NKp30 receptor by activated NK cells. J Exp Med 195(3):343–351 (2002).PubMedCrossRefGoogle Scholar
  16. 16.
    F. Gerosa, B. Baldani-Guerra, C. Nisii, V. Marchesini, G. Carra and G. Trinchieri. Reciprocal activating interaction between natural killer cells and dendritic cells. J Exp Med 195(3):327–333 (2002).PubMedCrossRefGoogle Scholar
  17. 17.
    D. Piccioli, S. Sbrana, E. Melandri and N.M. Valiante. Contact-dependent stimulation and inhibition of dendritic cells by natural killer cells. J Exp Med 195(3):335–341 (2002).PubMedCrossRefGoogle Scholar
  18. 18.
    M. Vitale, M. Della Chiesa, S. Carlomagno, C. Romagnani, A. Thiel, L. Moretta and A. Moretta. The small subset of CD56brightCD16-natural killer cells is selectively responsible for both cell proliferation and interferon-gamma production upon interaction with dendritic cells. Eur J Immunol 34(6):1715–1722 (2004).PubMedCrossRefGoogle Scholar
  19. 19.
    A. Moretta. Natural killer cells and dendritic cells: rendezvous in abused tissues. Nat Rev Immunol 2(12):957–964 (2002).PubMedCrossRefGoogle Scholar
  20. 20.
    M.A. Cooper, T.A. Fehniger, A. Fuchs, M. Colonna and M.A. Caligiuri. NK cell and DC interactions. Trends Immunol 25(1):47–52 (2004).PubMedCrossRefGoogle Scholar
  21. 21.
    L. Zitvogel. Dendritic and natural killer cells cooperate in the control/switch of innate immunity. J Exp Med 195(3):F9–F14 (2002).PubMedCrossRefGoogle Scholar
  22. 22.
    D.H. Raulet. Interplay of natural killer cells and their receptors with the adaptive immune response. Nat Immunol 5(10):996–1002 (2004).PubMedCrossRefGoogle Scholar
  23. 23.
    T. Walzer, M. Dalod, S.H. Robbins, L. Zitvogel and E. Vivier. Natural-killer cells and dendritic cells: “l’union fait la force”. Blood 106(7):2252–2258 (2005).PubMedCrossRefGoogle Scholar
  24. 24.
    M. Della Chiesa, S. Sivori, R. Castriconi, E. Marcenaro and A. Moretta. Pathogeninduced private conversations between natural killer and dendritic cells. Trends Microbiol 13(3):128–136 (2005).PubMedCrossRefGoogle Scholar
  25. 25.
    A. Moretta. The dialogue between human natural killer cells and dendritic cells. Curr Opin Immunol 17(3):306–311 (2005).PubMedCrossRefGoogle Scholar
  26. 26.
    A. Moretta, E. Marcenaro, S. Sivori, M. Della Chiesa, M. Vitale and L. Moretta. Early liaisons between cells of the innate immune system in inflamed peripheral tissues. Trends Immunol 26(12):668–675 (2005).PubMedCrossRefGoogle Scholar
  27. 27.
    S. Sivori, M. Falco, M. Della Chiesa, S. Carlomagno, M. Vitale, L. Moretta and A. Moretta. CpG and double-stranded RNA trigger human NK cells by Toll-like receptors: induction of cytokine release and cytotoxicity against tumors and dendritic cells. Proc Natl Acad Sci USA 101(27):10116–10121 (2004).PubMedCrossRefGoogle Scholar
  28. 28.
    K.N. Schmidt, B. Leung, M. Kwong, K.A. Zarember, S. Satyal, T.A. Navas, F. Wang and P.J. Godowski. APC-independent activation of NK cells by the Toll-like receptor 3 agonist double-stranded RNA. J Immunol 172(1):138–143 (2004).PubMedGoogle Scholar
  29. 29.
    S. Pisegna, G. Pirozzi, M. Piccoli, L. Frati, A. Santoni and G. Palmieri. p38 MAPK activation controls the TLR3-mediated up-regulation of cytotoxicity and cytokine production in human NK cells. Blood 104(13):4157–4164 (2004).PubMedCrossRefGoogle Scholar
  30. 30.
    S. Akira and K. Takeda. Toll-like receptor signalling. Nat Rev Immunol 4(7):499–511 (2004).PubMedCrossRefGoogle Scholar
  31. 31.
    F. Sallusto and A. Lanzavecchia. Mobilizing dendritic cells for tolerance. priming and chronic inflammation. J Exp Med 189(4):611–614 (1999).PubMedCrossRefGoogle Scholar
  32. 32.
    J. Banchereau, F. Briere, C. Caux, J. Davoust, S. Lebecque, Y.J. Liu, B. Pulendran and K. Palucka. Immunobiology of dendritic cells. Annu Rev Immunol 18:767–811 (2000).PubMedCrossRefGoogle Scholar
  33. 33.
    C. Reis e Sousa. Dendritic cells as sensors of infection. Immunity 14(5):495–498 (2001).PubMedCrossRefGoogle Scholar
  34. 34.
    G. Trinchieri. Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol 3(2):133–146 (2003).PubMedCrossRefGoogle Scholar
  35. 35.
    M. Della Chiesa, M. Vitale, S. Carlomagno, G. Ferlazzo, L. Moretta and A. Moretta. The natural killer cell-mediated killing of autologous dendritic cells is confined to a cell subset expressing CD94/NKG2A, but lacking inhibitory killer Ig-like receptors. Eur J Immunol 33(6):1657–1666 (2003).PubMedCrossRefGoogle Scholar
  36. 36.
    R.B. Mailliard, S.M. Alber, H. Shen, S.C. Watkins, J.M. Kirkwood, R.B. Herberman and P. Kailnski. IL-18-induced CD83+ CCR7+ NK helper cells. J Exp Med 200(7):941–953 (2005).CrossRefGoogle Scholar
  37. 37.
    A. Kaser, S. Kaser, N.C. Kaneider, B. Enrich, C.J. Wiedermann and H. Tilg. Interleukin-18 attracts plasmacytoid dendritic cells (DC2s) and promotes Th1 induction by DC2 through IL-18 receptor expression. Blood 103(2):648–655 (2004).PubMedCrossRefGoogle Scholar
  38. 38.
    F. Gerosa, A. Gobbi, P. Zorzi, S. Burg, F. Briere, G. Carra and G. Trinchieri. The reciprocal interaction of NK cells with plasmacytoid or myeloid dendritic cells profoundly affects innate resistance functions. J Immunol 174(2):727–734 (2005).PubMedGoogle Scholar
  39. 39.
    C. Romagnani, M. Della Chiesa, S. Kohler, B. Moewes, A. Radbruch, L. Moretta, A. Moretta and A. Thiel. Activation of human NK cells by plasmacytoid dendritic cells and its modulation by CD4+ T helper cells and CD4+ CD25hi T regulatory cells. Eur J Immunol 35(8):2452–2458 (2005).PubMedCrossRefGoogle Scholar
  40. 40.
    D. Jarrossay, G. Napolitani, M. Colonna, F. Sallusto and A. Lanzavecchia. Specialization and complementarity in microbial molecule recognition by human myeloid and plasmacytoid dendritic cells. Eur J Immunol 31(11):3388–3393 (2001).PubMedCrossRefGoogle Scholar
  41. 41.
    C. Asselin-Paturel and G. Trinchieri. Production of type I interferons: plasmacytoid dendritic cells and beyond. J Exp Med 202(4):461–465 (2005).PubMedCrossRefGoogle Scholar
  42. 42.
    A.M. Krieg. CpG motifs in bacterial DNA and their immune effects. Annu Rev Immunol 20:709–760 (2002).PubMedCrossRefGoogle Scholar
  43. 43.
    V. Supajatura, H. Ushio, A. Nakao, S. Akira, K. Okumura, C. Ra and H. Ogawa. Differential responses of mast cell Toll-like receptors 2 and 4 in allergy and innate immunity. J Clin Invest 109(10):1351–1359 (2002).PubMedCrossRefGoogle Scholar
  44. 44.
    M. Kulka, L. Alexopoulou, R.A. Flavell and D.D. Metcalfe. Activation of mast cells by double-stranded RNA: evidence for activation through Toll-like receptor 3. J Allergy Clin Immunol 114(1):174–182 (2004).PubMedCrossRefGoogle Scholar
  45. 45.
    J.S. Marshall. Mast-cell responses to pathogens. Nat Rev Immunol 4(10):787–799 (2004).PubMedCrossRefGoogle Scholar
  46. 46.
    K.P. van Gisbergen, T.B. Geijtenbeek and Y. van Kooyk. Close encounters of neutrophils and DCs. Trends Immunol 26(12):626–631 (2005).PubMedCrossRefGoogle Scholar
  47. 47.
    H. Nagase, S. Okugawa, Y. Ota, M. Yamaguchi, H. Tomizawa, K. Matsushima, K. Ohta, K. Yamamoto and K. Hirai. Expression and function of Toll-like receptors in eosinophils: activation by Toll-like receptor 7 ligand. J Immunol 171(8):3977–3982 (2003).PubMedGoogle Scholar
  48. 48.
    M. Colonna, G. Trinchieri and Y.J. Liu. Plasmacytoid dendritic cells in immunity. Nat Immunol 5(12):1219–1226 (2004).PubMedCrossRefGoogle Scholar
  49. 49.
    E. Marcenaro, M. Della Chiesa, F. Bellora, S. Parolini, R. Millo, L. Moretta and A. Moretta. IL-12 or IL-4 prime human NK cells to mediate functionally divergent interactions with dendritic cells or tumors. J Immunol 174(7):3992–3998 (2005).PubMedGoogle Scholar
  50. 50.
    R.B. Mailliard, Y.I. Son, R. Redlinger, P.T. Coates, A. Giermasz, P.A. Morel, W.J. Storkus and P. Kalinski. Dendritic cells mediate NK cell help for Th1 and CTL responses: two-signal requirement for the induction of NK cell helper function. J Immunol 171(5):2366–2373 (2003).PubMedGoogle Scholar
  51. 51.
    M. Vitale, M. Della Chiesa, S. Carlomagno, D. Pende, M. Arico, L. Moretta and A. Moretta. NK-dependent DC maturation is mediated by TNFalpha and IFNgamma released upon engagement of the NKp30 triggering receptor. Blood 106(2):566–571 (2005).PubMedCrossRefGoogle Scholar
  52. 52.
    S. Bennouna, S.K. Bliss, T.J. Curiel and E.Y. Denkers. Cross-talk in the innate immune system: neutrophils instruct recruitment and activation of dendritic cells during microbial infection. J Immunol 171(11):6052–6058 (2003).PubMedGoogle Scholar
  53. 53.
    K.P. van Gisbergen, M. Sanchez-Hernandez, T.B. Geijtenbeek and Y. van Kooyk. Neutrophils mediate immune modulation of dendritic cells through glycosylation-dependent interactions between Mac-1 and DC-SIGN. J Exp Med 201(8):1281–1292 (2005).PubMedCrossRefGoogle Scholar
  54. 54.
    M.A. Cassatella. The production of cytokines by polymorphonuclear neutrophils. Immunol Today 16(1):21–26 (1995).PubMedCrossRefGoogle Scholar
  55. 55.
    S. Bennouna and E.Y. Denkers. Microbial antigen triggers rapid mobilization of TNF-alpha to the surface of mouse neutrophils transforming them into inducers of high-level dendritic cell TNF-alpha production. J Immunol 174(8):4845–4851 (2005).PubMedGoogle Scholar
  56. 56.
    I. Sabroe, L.R. Prince, E.C. Jones, M.J. Horsburgh, S.J. Foster, S.N. Vogel, S.K. Dower and M.K. Whyte. Selective roles for Toll-like receptor (TLR)2 and TLR4 in the regulation of neutrophil activation and life span. J Immunol 170(10):5268–5275 (2003).PubMedGoogle Scholar
  57. 57.
    P. Scapini, J.A. Lapinet-Vera, S. Gasperini, F. Calzetti, F. Bazzoni and M.A. Cassatella. The neutrophil as a cellular source of chemokines. Immunol Rev 177:195–203 (2000).PubMedCrossRefGoogle Scholar
  58. 58.
    S.J. Galli, S. Nakae and M. Tsai. Mast cells in the development of adaptive immune responses. Nat Immunol 6(2):135–142 (2005).PubMedCrossRefGoogle Scholar
  59. 59.
    C.A. Biron, K.B. Nguyen, G.C. Pien, L.P. Cousens and T.P. Salazar-Mather. Natural killer cells in antiviral defense: function and regulation by innate cytokines. Annu Rev Immunol 17:189–220 (1999).PubMedCrossRefGoogle Scholar
  60. 60.
    S.L. Constant and K. Bottomly. Induction of Th1 and Th2 CD4+ T cell responses: the alternative approaches. Annu Rev Immunol 15:297–322 (1997).PubMedCrossRefGoogle Scholar
  61. 61.
    E. Marcenaro, B. Ferranti and A. Moretta. NK-DC interaction: on the usefulness of auto-aggression. Autoimmun Rev 4(8):520–525 (2005).PubMedCrossRefGoogle Scholar
  62. 62.
    D. Dombrowicz and M. Capron. Eosinophils, allergy and parasites. Curr Opin Immunol 13(6):716–720 (2001).PubMedCrossRefGoogle Scholar
  63. 63.
    C. Bandeira-Melo and P.F. Weller. Mechanisms of eosinophil cytokine release. Mem Inst Oswaldo Cruz 100(Suppl 1)73–81 (2005).PubMedGoogle Scholar
  64. 64.
    B. Lamkhioued, A.S. Gounni, D. Aldebert, E. Delaporte, L. Prin, A. Capron and M. Capron. Synthesis of type 1 (IFN gamma) and type 2 (IL-4, IL-5, and IL-10) cytokines by human eosinophils. Ann NY Acad Sci 796:203–208 (1996).PubMedCrossRefGoogle Scholar
  65. 65.
    C. Bandeira-Melo, K. Sugiyama, L.J. Woods and P.F. Weller. Cutting edge: eotaxin elicits rapid vesicular transport-mediated release of preformed IL-4 from human eosinophils. J Immunol 166(8):4813–4817 (2001).PubMedGoogle Scholar
  66. 66.
    M. Grewe, W. Czech, A. Morita, T. Werfel, M. Klammer, A. Kapp, T. Ruzicka, E. Schopf and J. Krutmann. Human eosinophils produce biologically active IL-12: implications for control of T cell responses. J Immunol 161(1):415–420 (1998).PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Emanuela Marcenaro
    • 1
    • 2
  • Mariella Della Chiesa
    • 1
  • Alessandra Dondero
    • 1
  • Bruna Ferranti
    • 1
  • Alessandro Moretta
    • 1
    • 3
    Email author
  1. 1.Dipartimento di Medicina SperimentaleUniversità degli Studi di GenovaItaly
  2. 2.Istituto Giannina GasliniGenovaItaly
  3. 3.Centro di Eccellenza per le Ricerche BiomedicheUniversità degli Studi di GenovaGenovaItaly

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