Signal Transduction in DC Differentiation: Winged Messengers and Achilles’ Heel

  • Inna Lindner
  • Pedro J. Cejas
  • Louise M. Carlson
  • Julie Torruellas
  • Gregory V. Plano
  • Kelvin P. Lee
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 590)


Dendritic cells (DC) are centrally involved in the initiation and regulation of the adaptive immune response, and different DC can have markedly different (e.g., opposing) function. Acquisition of specific functions is likely to be a result of both nature and nurture, namely differentiation of progenitors into distinct DC subsets as well as the influence of environmental signals. This is not unlike what is seen for T and B cells. This review will focus on the signal transduction pathways that allow an unusually wide range of hematopoietic progenitors to differentiate into DC, the functional characteristics regulated by these pathways, and the ability of pathogens to alter DC function by subverting these pathways during progenitor→DC differentiation.


Dendritic Cell Yersinia Enterocolitica Human Dendritic Cell Dendritic Cell Subset Dendritic Cell Differentiation 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

7. References

  1. 1.
    J. Sprent, H. Kishimoto. The thymus and negative selection. Immunol Rev 185:126–135 (2002).PubMedGoogle Scholar
  2. 2.
    D. Mathis and C. Benoist. Back to central tolerance. Immunity 20(5):509–516 (2004).PubMedGoogle Scholar
  3. 3.
    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(4):767–811 (2000).PubMedGoogle Scholar
  4. 4.
    J. Banchereau and R.M. Steinman. Dendritic cells and the control of immunity. Nature 392(6673):245–252 (1998).PubMedGoogle Scholar
  5. 5.
    M. Rescigno, C. Winzler, D. Delia, C. Mutini, M. Lutz and P. Ricciardi-Castagnoli. Dendritic cell maturation is required for initiation of the immune response. J Leukoc Biol 61(4):415–421 (1997).PubMedGoogle Scholar
  6. 6.
    P. Matzinger. Tolerance, danger, and the extended family. Annu Rev Immunol 12:991–1045 (1994).PubMedGoogle Scholar
  7. 7.
    C. Winzler, P. Rovere, M. Rescigno, F. Granucci, G. Penna, L. Adorini, V.S. Zimmermann, J. Davoust and P. Ricciardi-Castagnoli. Maturation stages of mouse dendritic cells in growth factor-dependent long-term cultures. J Exp Med 185(2):317–328 (1997).PubMedGoogle Scholar
  8. 8.
    E.C. de Jong, H.H. Smits and M.L. Kapsenberg. Dendritic cell-mediated T cell polarization. Springer Semin Immunopathol 26(3):289–307 (2005).PubMedGoogle Scholar
  9. 9.
    K.M. Murphy, W. Ouyang, J.D. Farrar, J. Yang, S. Ranganath, H. Asnagli, M. Afkarian and T.L. Murphy. Signaling and transcription in T helper development. Annu Rev Immunol 18:451–494 (2000).PubMedGoogle Scholar
  10. 10.
    M. Moser and K.M. Murphy. Dendritic cell regulation of TH1–TH2 development. Nat Immunol 1(3):199–205 (2000).PubMedGoogle Scholar
  11. 11.
    A. D’Andrea, X. Ma, M. Aste-Amezaga, C. Paganin and G. Trinchieri. Stimulatory and inhibitory effects of interleukin (IL)-4 and IL-13 on the production of cytokines by human peripheral blood mononuclear cells: priming for IL-12 and tumor necrosis factor alpha production. J Exp Med 181(2):537–546 (1995).PubMedGoogle Scholar
  12. 12.
    C. Heufler, F. Koch, U. Stanzl, G. Topar, M. Wysocka, G. Trinchieri, A. Enk, R.M. Steinman, N. Romani and G. Schuler. Interleukin-12 is produced by dendritic cells and mediates T helper 1 development as well as interferon-gamma production by T helper 1 cells. Eur J Immunol 26(3):659–668 (1996).PubMedGoogle Scholar
  13. 13.
    F. Koch, U. Stanzl, P. Jennewein, K. Janke, C. Heufler, E. Kampgen, N. Romani and G. Schuler. High level IL-12 production by murine dendritic cells: upregulation via MHC class II and CD40 molecules and downregulation by IL-4 and IL-10. J Exp Med 184(2):741–746 (1996).PubMedGoogle Scholar
  14. 14.
    M. Croft, D.D. Duncan and S.L. Swain. Response of naive antigen-specific CD4+ T cells in vitro: characteristics and antigen-presenting cell requirements. J Exp Med 176(5):1431–1437 (1992).PubMedGoogle Scholar
  15. 15.
    S.E. Macatonia, C.S. Hsieh, K.M. Murphy and A. O’Garra. Dendritic cells and macrophages are required for Th1 development of CD4+ T cells from alpha beta TCR transgenic mice: IL-12 substitution for macrophages to stimulate IFN-gamma production is IFN-gamma-dependent. Int Immunol 5(9):1119–1128 (1993).PubMedGoogle Scholar
  16. 16.
    A.H. Enk. Dendritic cells in tolerance induction. Immunol Lett 99(1):8–11 (2005).PubMedGoogle Scholar
  17. 17.
    M.V. Dhodapkar, R.M. Steinman, J. Krasovsky, C. Munz and N. Bhardwaj. Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J Exp Med 193(2):233–238 (2001).PubMedGoogle Scholar
  18. 18.
    M.B. Lutz, R.M. Suri, M. Niimi, A.L. Ogilvie, N.A. Kukutsch, S. Rossner, G. Schuler and J.M. Austyn. Immature dendritic cells generated with low doses of GMCSF in the absence of IL-4 are maturation resistant and prolong allograft survival in vivo. Eur J Immunol 30(7):1813–1822 (2000).PubMedGoogle Scholar
  19. 19.
    H. Jonuleit, E. Schmitt, G. Schuler, J. Knop and A.H. Enk. Induction of interleukin 10-producing, nonproliferating CD4(+) T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells. J Exp Med 192(9):1213–1222 (2000).PubMedGoogle Scholar
  20. 20.
    K. Steinbrink, M. Wolfl, H. Jonuleit, J. Knop and A.H. Enk. Induction of tolerance by IL-10-treated dendritic cells. J Immunol 159(10):4772–4780 (1997).PubMedGoogle Scholar
  21. 21.
    L. Piemonti, P. Monti, P. Allavena, M. Sironi, L. Soldini, B.E. Leone, C. Socci and V. Di Carlo. Glucocorticoids affect human dendritic cell differentiation and maturation. J Immunol 162(11):6473–6481 (1999).PubMedGoogle Scholar
  22. 22.
    L. Piemonti, P. Monti, M. Sironi, P. Fraticelli, B.E. Leone, E. Dal Cin, P. Allavena and V. Di Carlo. Vitamin D3 affects differentiation, maturation, and function of human monocyte-derived dendritic cells. J Immunol 164(9):4443–4451 (2000).PubMedGoogle Scholar
  23. 23.
    P. Kalinski, C.M. Hilkens, A. Snijders, F.G. Snijdewint and M.L. Kapsenberg. IL-12-deficient dendritic cells, generated in the presence of prostaglandin E2, promote type 2 cytokine production in maturing human naive T helper cells. J Immunol 159(1):28–35 (1997).PubMedGoogle Scholar
  24. 24.
    A.H. Enk, H. Jonuleit, J. Saloga and J. Knop. Dendritic cells as mediators of tumor-induced tolerance in metastatic melanoma. Int J Cancer 73(3):309–316 (1997).PubMedGoogle Scholar
  25. 25.
    C. Rastellini, L. Lu, C. Ricordi, T.E. Starzl, A.S. Rao and A.W. Thomson. Granulocyte/macrophage colony-stimulating factor-stimulated hepatic dendritic cell progenitors prolong pancreatic islet allograft survival. Transplantation 60(11):1366–1370 (1995).PubMedGoogle Scholar
  26. 26.
    E. Martin, B. O’Sullivan, P. Low and R. Thomas. Antigen-specific suppression of a primed immune response by dendritic cells mediated by regulatory T cells secreting interleukin-10. Immunity 18(1):155–167 (2003).PubMedGoogle Scholar
  27. 27.
    A.G. Thompson, B.J. O’Sullivan, H. Beamish and R. Thomas. T cells signaled by NF-kappa B-dendritic cells are sensitized not anergic to subsequent activation. J Immunol 173(3):1671–1680 (2004).PubMedGoogle Scholar
  28. 28.
    D. Gabrilovich, T. Ishida, T. Oyama, S. Ran, V. Kravtsov, S. Nadaf and D.P. Carbone. Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo. Blood 92(11):4150–4166 (1998).PubMedGoogle Scholar
  29. 29.
    K. Shortman and Y.J. Liu. Mouse and human dendritic cell subtypes. Nat Rev Immunol 2(3):151–161 (2002).PubMedGoogle Scholar
  30. 30.
    Q. Huang, D. Liu, P. Majewski, L.C. Schulte, J.M. Korn, R.A. Young, E.S. Lander and N. Hacohen. The plasticity of dendritic cell responses to pathogens and their components. Science 294(5543):870–875 (2001).PubMedGoogle Scholar
  31. 31.
    Y.J. Liu. Dendritic cell subsets and lineages, and their functions in innate and adaptive immunity. Cell 106(3):259–262 (2001).PubMedGoogle Scholar
  32. 32.
    R. Maldonado-Lopez, T. De Smedt, P. Michel, J. Godfroid, B. Pajak, C. Heirman, K. Thielemans, O. Leo, J. Urbain and M. Moser. CD8alpha+ and CD8alpha-subclasses of dendritic cells direct the development of distinct T helper cells in vivo. J Exp Med 189(3):587–592 (1999).PubMedGoogle Scholar
  33. 33.
    B. Pulendran, J.L. Smith, G. Caspary, K. Brasel, D. Pettit, E. Maraskovsky and C.R. Maliszewski. Distinct dendritic cell subsets differentially regulate the class of immune response in vivo. Proc Natl Acad Sci USA 96(3):1036–1041 (1999).PubMedGoogle Scholar
  34. 34.
    I. Szatmari, P. Gogolak, J.S. Im, B. Dezso, E. Rajnavolgyi and L. Nagy. Activation of PPARgamma specifies a dendritic cell subtype capable of enhanced induction of iNKT cell expansion. Immunity 21(1):95–106 (2004).PubMedGoogle Scholar
  35. 35.
    P. Cheng, Y. Nefedova, L. Miele, B.A. Osborne and D. Gabrilovich. Notch signaling is necessary but not sufficient for differentiation of dendritic cells. Blood 102(12):3980–3988 (2003).PubMedGoogle Scholar
  36. 36.
    K.L. Anderson, H. Perkin, C.D. Surh, S. Venturini, R.A. Maki and B.E. Torbett. Transcription factor PU.1 is necessary for development of thymic and myeloid progenitor-derived dendritic cells. J Immunol 164(4):1855–1861 (2000).PubMedGoogle Scholar
  37. 37.
    B. Almand, J.I. Clark, E. Nikitina, J. van Beynen, N.R. English, S.C. Knight, D.P. Carbone and D.I. Gabrilovich. Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer. J Immunol 166(1):678–689 (2001).PubMedGoogle Scholar
  38. 38.
    C. Caux, C. Dezutter-Dambuyant, D. Schmitt and J. Banchereau. GM-CSF and TNF-alpha cooperate in the generation of dendritic Langerhans cells. Nature 360(6401):258–261 (1992).PubMedGoogle Scholar
  39. 39.
    T.A. Davis, A.A. Saini, P.J. Blair, B.L. Levine, N. Craighead, D.M. Harlan, C.H. June and K.P. Lee, Phorbol esters induce differentiation of human CD34+ hemopoietic progenitors to dendritic cells: evidence for protein kinase C-mediated signaling. J Immunol 160(8):3689–3697 (1998).PubMedGoogle Scholar
  40. 40.
    R.E. Ryncarz and C. Anasetti. Expression of CD86 on human marrow CD34(+) cells identifies immunocompetent committed precursors of macrophages and dendritic cells. Blood 91(10):3892–3900 (1998).PubMedGoogle Scholar
  41. 41.
    M.G. Manz, D. Traver, K. Akashi, M. Merad, T. Miyamoto, E.G. Engleman and I.L. Weissman. Dendritic cell development from common myeloid progenitors. Ann NY Acad Sci 938(167–173; discussion 173–164) (2001).PubMedGoogle Scholar
  42. 42.
    M.G. Manz, D. Traver, T. Miyamoto, I.L. Weissman and K. Akashi. Dendritic cell potentials of early lymphoid and myeloid progenitors. Blood 97(11):3333–3341 (2001).PubMedGoogle Scholar
  43. 43.
    J.W. Young, P. Szabolcs and M.A. Moore. Identification of dendritic cell colonyforming units among normal human CD34+ bone marrow progenitors that are expanded by c-kit-ligand and yield pure dendritic cell colonies in the presence of granulocyte/macrophage colony-stimulating factor and tumor necrosis factor alpha. J Exp Med 182(4):1111–1119 (1995).PubMedGoogle Scholar
  44. 44.
    S.M. Kiertscher and M.D. Roth. Human CD14+ leukocytes acquire the phenotype and function of antigen-presenting dendritic cells when cultured in GM-CSF and IL-4. J Leukoc Biol 59(2):208–218 (1996).PubMedGoogle Scholar
  45. 45.
    L.J. Zhou and T.F. Tedder. CD14+ blood monocytes can differentiate into functionally mature CD83+ dendritic cells. Proc Natl Acad Sci USA 93(6):2588–2592 (1996).PubMedGoogle Scholar
  46. 46.
    L. Oehler, O. Majdic, W.F. Pickl, J. Stockl, E. Riedl, J. Drach, K. Rappersberger, K. Geissler and W. Knapp. Neutrophil granulocyte-committed cells can be driven to acquire dendritic cell characteristics. J Exp Med 187(7):1019–1028 (1998).PubMedGoogle Scholar
  47. 47.
    B.C. Hulette, G. Rowden, C.A. Ryan, C.M. Lawson, S.M. Dawes, G.M. Ridder and G.F. Gerberick. Cytokine induction of a human acute myelogenous leukemia cell line (KG-1) to a CD1a+ dendritic cell phenotype. Arch Dermatol Res 293(3):147–158 (2001).PubMedGoogle Scholar
  48. 48.
    A. Cignetti, E. Bryant, B. Allione, A. Vitale, R. Foa and M.A. Cheever. CD34(+) acute myeloid and lymphoid leukemic blasts can be induced to differentiate into dendritic cells. Blood 94(6):2048–2055 (1999).PubMedGoogle Scholar
  49. 49.
    B.A. Choudhury, J.C. Liang, E.K. Thomas, L. Flores-Romo, Q.S. Xie, K. Agusala, S. Sutaria, I. Sinha, R.E. Champlin and D.F. Claxton. Dendritic cells derived in vitro from acute myelogenous leukemia cells stimulate autologous, antileukemic T-cell responses. Blood 93(3):780–786 (1999).PubMedGoogle Scholar
  50. 50.
    A. Charbonnier, B. Gaugler, D. Sainty, M. Lafage-Pochitaloff and D. Olive. Human acute myeloblastic leukemia cells differentiate in vitro into mature dendritic cells and induce the differentiation of cytotoxic T cells against autologous leukemias. Eur J Immunol 29(8):2567–2578 (1999).PubMedGoogle Scholar
  51. 51.
    B.D. Harrison, J.A. Adams, M. Briggs, M.L. Brereton and J.A. Yin. Stimulation of autologous proliferative and cytotoxic T-cell responses by “leukemic dendritic cells” derived from blast cells in acute myeloid leukemia. Blood 97(9):2764–2771 (2001).PubMedGoogle Scholar
  52. 52.
    N. Bendriss-Vermare, C. Barthelemy, I. Durand, C. Bruand, C. Dezutter-Dambuyant, N. Moulian, S. Berrih-Aknin, C. Caux, G. Trinchieri and F. Briere. Human thymus contains IFN-alpha-producing CD11c(-), myeloid CD11c(+), and mature interdigitating dendritic cells. J Clin Invest 107(7):835–844 (2001).PubMedGoogle Scholar
  53. 53.
    A. Galy, M. Travis, D. Cen and B. Chen. Human T, B, natural killer, and dendritic cells arise from a common bone marrow progenitor cell subset. Immunity 3(4):459–473 (1995).PubMedGoogle Scholar
  54. 54.
    F. Sallusto and A. Lanzavecchia. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colonystimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha. J Exp Med 179(4):1109–1118 (1994).PubMedGoogle Scholar
  55. 55.
    M.C. Rissoan, V. Soumelis, N. Kadowaki, G. Grouard, F. Briere, R. de Waal Malefyt and Y.J. Liu. Reciprocal control of T helper cell and dendritic cell differentiation. Science 283(5405):1183–1186 (1999).PubMedGoogle Scholar
  56. 56.
    G.J. Randolph, S. Beaulieu, S. Lebecque, R.M. Steinman and W.A. Muller. Differentiation of monocytes into dendritic cells in a model of transendothelial trafficking. Science 282(5388):480–483 (1998).PubMedGoogle Scholar
  57. 57.
    G. Grouard, M.C. Rissoan, L. Filgueira, I. Durand, J. Banchereau and Y.J. Liu. The enigmatic plasmacytoid T cells develop into dendritic cells with interleukin (IL)-3 and CD40-ligand. J Exp Med 185(6):1101–1111 (1997).PubMedGoogle Scholar
  58. 58.
    C. Caux, C. Massacrier, B. Vanbervliet, B. Dubois, B. de Saint-Vis, C. Dezutter-Dambuyant, C. Jacquet, D. Schmitt and J. Banchereau. CD34+ hematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to GM-CSF+TNF alpha. Adv Exp Med Biol 417(5):21–25 (1997).PubMedGoogle Scholar
  59. 59.
    C. Caux, B. Vanbervliet, C. Massacrier, B. Dubois, C. Dezutter-Dambuyant, D. Schmitt and J. Banchereau. Characterization of human CD34+ derived dendritic/Langerhans cells (D-Lc). Adv Exp Med Biol 378:1–5 (1995).PubMedGoogle Scholar
  60. 60.
    M. Waclavicek, A. Berer, L. Oehler, J. Stockl, E. Schloegl, O. Majdic and W. Knapp. Calcium ionophore: a single reagent for the differentiation of primary human acute myelogenous leukaemia cells towards dendritic cells. Br J Haematol 114(2):466–473 (2001).PubMedGoogle Scholar
  61. 61.
    B.J. Czerniecki, C. Carter, L. Rivoltini, G.K. Koski, H.I. Kim, D.E. Weng, J.G. Roros, Y.M. Hijazi, S. Xu, S.A. Rosenberg and P.A. Cohen. Calcium ionophore-treated peripheral blood monocytes and dendritic cells rapidly display characteristics of activated dendritic cells. J Immunol 159(8):3823–3837 (1997).PubMedGoogle Scholar
  62. 62.
    G.K. Koski, G.N. Schwartz, D.E. Weng, B.J. Czerniecki, C. Carter, R.E. Gress and P.A. Cohen. Calcium mobilization in human myeloid cells results in acquisition of individual dendritic cell-like characteristics through discrete signaling pathways. J Immunol 163(1):82–92 (1999).PubMedGoogle Scholar
  63. 63.
    D.C. St Louis, J.B. Woodcock, G. Fransozo, P.J. Blair, L.M. Carlson, M. Murillo, M.R. Wells, A.J. Williams, D.S. Smoot, S. Kaushal, J.L. Grimes, D.M. Harlan, J.P. Chute, C.H. June, U. Siebenlist and K.P. Lee. Evidence for distinct intracellular signaling pathways in CD34+ progenitor to dendritic cell differentiation from a human cell line model. J Immunol 162(6):3237–3248 (1999).PubMedGoogle Scholar
  64. 64.
    L. Flores-Romo, P. Bjorck, V. Duvert, C. van Kooten, S. Saeland and J. Banchereau. CD40 ligation on human cord blood CD34+ hematopoietic progenitors induces their proliferation and differentiation into functional dendritic cells. J Exp Med 185(2):341–349 (1997).PubMedGoogle Scholar
  65. 65.
    L. Oehler, A. Berer, M. Kollars, F. Keil, M. Konig, M. Waclavicek, O. Haas, W. Knapp, K. Lechner and K. Geissler. Culture requirements for induction of dendritic cell differentiation in acute myeloid leukemia. Ann Hematol 79(7):355–362 (2000).PubMedGoogle Scholar
  66. 66.
    M. Heinzinger, C.F. Waller, A. von den Berg, A. Rosenstiel and W. Lange. Generation of dendritic cells from patients with chronic myelogenous leukemia. Ann Hematol 78(4):181–186 (1999).PubMedGoogle Scholar
  67. 67.
    D. Vremec and K. Shortman. Dendritic cell subtypes in mouse lymphoid organs: cross-correlation of surface markers, changes with incubation, and differences among thymus, spleen, and lymph nodes. J Immunol 159(2):565–573 (1997).PubMedGoogle Scholar
  68. 68.
    E. Maraskovsky, K. Brasel, M. Teepe, E.R. Roux, S.D. Lyman, K. Shortman and H.J. McKenna. Dramatic increase in the numbers of functionally mature dendritic cells in Flt3 ligand-treated mice: multiple dendritic cell subpopulations identified. J Exp Med 184(5):1953–1962 (1996).PubMedGoogle Scholar
  69. 69.
    B. Pulendran, J. Lingappa, M.K. Kennedy, J. Smith, M. Teepe, A. Rudensky, C.R. Maliszewski and E. Maraskovsky. Developmental pathways of dendritic cells in vivo: distinct function, phenotype, and localization of dendritic cell subsets in FLT3 ligand-treated mice. J Immunol 159(5):2222–2231 (1997).PubMedGoogle Scholar
  70. 70.
    A. Curti, M. Fogli, M. Ratta, S. Tura and R.M. Lemoli. Stem cell factor and FLT3-ligand are strictly required to sustain the long-term expansion of primitive CD34+DR-dendritic cell precursors. J Immunol 166(2):848–854 (2001).PubMedGoogle Scholar
  71. 71.
    J. Taieb, K. Maruyama, C. Borg, M. Terme and L. Zitvogel, Imatinib mesylate impairs Flt3L-mediated dendritic cell expansion and antitumor effects in vivo. Blood 103(5):1966–1967 [author reply, 1967] (2004).PubMedGoogle Scholar
  72. 72.
    K. Saraya and C.D. Reid. Stem cell factor and the regulation of dendritic cell production from CD34+ progenitors in bone marrow and cord blood. Br J Haematol 93(2):258–264 (1996).PubMedGoogle Scholar
  73. 73.
    S. Akira, K. Takeda and T. Kaisho. Toll-like receptors: critical proteins linking innate and acquired immunity. Nat Immunol 2(8):675–680 (2001).PubMedGoogle Scholar
  74. 74.
    G.M. Zou and Y.K. Tam, Cytokines in the generation and maturation of dendritic cells: recent advances. Eur Cytokine Network 13(2):186–199 (2002).Google Scholar
  75. 75.
    B. Eibl, S. Ebner, C. Duba, G. Bock, N. Romani, M. Erdel, A. Gachter, D. Niederwieser and G. Schuler. Dendritic cells generated from blood precursors of chronic myelogenous leukemia patients carry the Philadelphia translocation and can induce a CML-specific primary cytotoxic T-cell response. Genes Chromosomes Cancer 20(3):215–223 (1997).PubMedGoogle Scholar
  76. 76.
    A. Choudhury, A. Toubert, S. Sutaria, D. Charron, R.E. Champlin and D.F. Claxton. Human leukemia-derived dendritic cells: ex-vivo development of specific antileukemic cytotoxicity. Crit Rev Immunol 18(1–2):121–131 (1998).PubMedGoogle Scholar
  77. 77.
    F. Santiago-Schwarz, D.L. Coppock, A.A. Hindenburg and J. Kern. Identification of a malignant counterpart of the monocyte-dendritic cell progenitor in an acute myeloid leukemia. Blood 84(9):3054–3062 (1994).PubMedGoogle Scholar
  78. 78.
    C. Wang, H.M. Al-Omar, L. Radvanyi, A. Banerjee, D. Bouman, J. Squire and H.A. Messner. Clonal heterogeneity of dendritic cells derived from patients with chronic myeloid leukemia and enhancement of their T-cells stimulatory activity by IFN-alpha. Exp Hematol 27(7):1176–1184 (1999).PubMedGoogle Scholar
  79. 79.
    A. Cignetti, A. Vallario, I. Roato, P. Circosta, B. Allione, L. Casorzo, P. Ghia and F. Caligaris-Cappio. Leukemia-derived immature dendritic cells differentiate into functionally competent mature dendritic cells that efficiently stimulate T cell responses. J Immunol 173(4):2855–2865 (2004).PubMedGoogle Scholar
  80. 80.
    Y. Laouar, T. Welte, X.Y. Fu and R.A. Flavell. STAT3 is required for Flt3L-dependent dendritic cell differentiation. Immunity 19(6):903–912 (2003).PubMedGoogle Scholar
  81. 81.
    L. Wu, A. Nichogiannopoulou, K. Shortman and K. Georgopoulos. Cellautonomous defects in dendritic cell populations of Ikaros mutant mice point to a developmental relationship with the lymphoid lineage. Immunity 7(4):483–492 (1997).PubMedGoogle Scholar
  82. 82.
    Y. Laouar, I.N. Crispe and R.A. Flavell. Overexpression of IL-7R alpha provides a competitive advantage during early T-cell development. Blood 103(6):1985–1994 (2004).PubMedGoogle Scholar
  83. 83.
    R. Schotte, M.C. Rissoan, N. Bendriss-Vermare, J.M. Bridon, T. Duhen, K. Weijer, F. Briere and H. Spits. The transcription factor Spi-B is expressed in plasmacytoid DC precursors and inhibits T-, B-, and NK-cell development. Blood 101(3):1015–1023 (2003).PubMedGoogle Scholar
  84. 84.
    Y. Takai, A. Kishimoto, Y. Iwasa, Y. Kawahara, T. Mori and Y. Nishizuka. Calcium-dependent activation of a multifunctional protein kinase by membrane phospholipids. J Biol Chem 254(10):3692–3695 (1979).PubMedGoogle Scholar
  85. 85.
    Y. Takai, A. Kishimoto, U. Kikkawa, T. Mori and Y. Nishizuka. Unsaturated diacylglycerol as a possible messenger for the activation of calcium-activated, phospholipid-dependent protein kinase system. Biochem Biophys Res Commun 91(4):1218–1224 (1979).PubMedGoogle Scholar
  86. 86.
    M. Castagna, Y. Takai, K. Kaibuchi, K. Sano, U. Kikkawa and Y. Nishizuka. Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem 257(13):7847–7851 (1982).PubMedGoogle Scholar
  87. 87.
    A.S. Kraft and W.B. Anderson. Phorbol esters increase the amount of Ca2+, phospholipid-dependent protein kinase associated with plasma membrane. Nature 301(5901):621–623 (1983).PubMedGoogle Scholar
  88. 88.
    M. Spitaler and D.A. Cantrell. Protein kinase C and beyond. Nat Immunol 5(8):785–790 (2004).PubMedGoogle Scholar
  89. 89.
    W.S. Liu and C.A. Heckman. The sevenfold way of PKC regulation. Cell Signal 10(8):529–542 (1998).PubMedGoogle Scholar
  90. 90.
    D. Schechtman and D. Mochly-Rosen. Adaptor proteins in protein kinase C-mediated signal transduction. Oncogene 20(44):6339–6347 (2001).PubMedGoogle Scholar
  91. 91.
    J.C. Yan, Z.G. Wu, X.T. Kong, R.Q. Zong and L.Z. Zhang. Effect of CD40-CD40 ligand interaction on diacylglycerol-protein kinase C signal transduction pathway and intracellular calcium in cultured human monocytes. Acta Pharmacol Sin 24(7):687–691 (2003).PubMedGoogle Scholar
  92. 92.
    N. Geijsen, M. Spaargaren, J.A. Raaijmakers, J.W. Lammers, L. Koenderman and P.J. Coffer, Association of RACK1 and PKCbeta with the common beta-chain of the IL-5/IL-3/GM-CSF receptor. Oncogene 18(36):5126–5130 (1999).PubMedGoogle Scholar
  93. 93.
    A.L. Goodell, H.S. Oh, S.A. Meyer and R.C. Smart. Epidermal protein kinase C-beta 2 is highly sensitive to downregulation and is exclusively expressed in Langerhans cells: downregulation is associated with attenuated contact hypersensitivity. J Invest Dermatol 107(3):354–359 (1996).PubMedGoogle Scholar
  94. 94.
    P.J. Cejas, L.M. Carlson, J. Zhang, S. Padmanabhan, D. Kolonias, I. Lindner, S. Haley, L.H. Boise and K.P. Lee. Protein kinase C betaII plays an essential role in dendritic cell differentiation and autoregulates its own expression. J Biol Chem 280(31):28412–28423 (2005).PubMedGoogle Scholar
  95. 95.
    G. Ramadan, R.E. Schmidt and J. Schubert. In vitro generation of human CD86+ dendritic cells from CD34+ haematopoietic progenitors by PMA and in serum-free medium. Clin Exp Immunol 125(2):237–244 (2001).PubMedGoogle Scholar
  96. 96.
    I. Lindner, M.A. Kharfan-Dabaja, E. Ayala, D. Kolonias, L.M. Carlson, Y. Beazer-Barclay, U. Scherf, J.H. Hnatyszyn and K.P. Lee, Induced dendritic cell differentiation of chronic myeloid leukemia blasts is associated with down-regulation of BCRABL. J Immunol 171(4):1780–1791 (2003).PubMedGoogle Scholar
  97. 97.
    M. Kharfan-Dabaja, E. Ayala, I. Lindner, P.J. Cejas, N.J. Bahlis, D. Kolonias, L.M. Carlson and K.P. Lee. Differentiation of acute and chronic myeloid leukemic blasts into the dendritic cell lineage: analysis of various differentiation-inducing signals. Cancer Immunol Immunother 54(1):25–36 (2005).PubMedGoogle Scholar
  98. 98.
    P.J. Cejas, L.M. Carlson, D. Kolonias, J. Zhang, I. Lindner, D.D. Billadeau, L.H. Boise and K.P. Lee. Regulation of RelB expression during the initiation of dendritic cell differentiation. Mol Cell Biol 25(17):7900–7916 (2005).PubMedGoogle Scholar
  99. 99.
    A. Cariappa, L. Chen, K. Haider, M. Tang, E. Nebelitskiy, S.T. Moran and S. Pillai. A catalytically inactive form of protein kinase C-associated kinase/receptor interacting protein 4, a protein kinase C beta-associated kinase that mediates NF-kappa B activation, interferes with early B cell development. J Immunol 171(4):1875–1880 (2003).PubMedGoogle Scholar
  100. 100.
    A.K. Olsson, K. Vadhammar and E. Nanberg. Activation and protein kinase C-dependent nuclear accumulation of ERK in differentiating human neuroblastoma cells. Exp Cell Res 256(2):454–467 (2000).PubMedGoogle Scholar
  101. 101.
    T.T. Su, B. Guo, Y. Kawakami, K. Sommer, K. Chae, L.A. Humphries, R.M. Kato, S. Kang, L. Patrone, R. Wall, M. Teitell, M. Leitges, T. Kawakami and D.J. Rawlings. PKC-beta controls I kappa B kinase lipid raft recruitment and activation in response to BCR signaling. Nat Immunol 3(8):780–786 (2002).PubMedGoogle Scholar
  102. 102.
    A. Kumar, T.C. Chambers, B.A. Cloud-Heflin and K.D. Mehta. Phorbol ester-induced low density lipoprotein receptor gene expression in HepG2 cells involves protein kinase C-mediated p42/44 MAP kinase activation. J Lipid Res 38(11):2240–2248 (1997).PubMedGoogle Scholar
  103. 103.
    J. Xie, Y. Wang, M.E. Freeman 3rd, B. Barlogie and Q. Yi. Beta 2-microglobulin as a negative regulator of the immune system: high concentrations of the protein inhibit in vitro generation of functional dendritic cells. Blood 101(10):4005–4012 (2003).PubMedGoogle Scholar
  104. 104.
    L. Wu, A. D’Amico, K.D. Winkel, M. Suter, D. Lo and K. Shortman. RelB is essential for the development of myeloid-related CD8alpha-dendritic cells but not of lymphoid-related CD8alpha+ dendritic cells. Immunity 9(6):839–847 (1998).PubMedGoogle Scholar
  105. 105.
    J. Xie, J. Qian, S. Wang, M.E. Freeman 3rd, J. Epstein and Q. Yi. Novel and detrimental effects of lipopolysaccharide on in vitro generation of immature dendritic cells: involvement of mitogen-activated protein kinase p38. J Immunol 171(9):4792–4800 (2003).PubMedGoogle Scholar
  106. 106.
    J. Xie, J. Qian, J. Yang, S. Wang, M.E. Freeman 3rd and Q. Yi. Critical roles of Raf/MEK/ERK and PI3K/AKT signaling and inactivation of p38 MAP kinase in the differentiation and survival of monocyte-derived immature dendritic cells. Exp Hematol 33(5):564–572 (2005).PubMedGoogle Scholar
  107. 107.
    W. Lim, W. Ma, K. Gee, S. Aucoin, D. Nandan, F. Diaz-Mitoma, M. Kozlowski and A. Kumar. Distinct role of p38 and c-Jun N-terminal kinases in IL-10-dependent and IL-10-independent regulation of the costimulatory molecule B7.2 in lipopolysaccharide-stimulated human monocytic cells. J Immunol 168(4):1759–1769 (2002).PubMedGoogle Scholar
  108. 108.
    K. Sato, H. Nagayama, K. Tadokoro, T. Juji and T.A. Takahashi. Extracellular signal-regulated kinase, stress-activated protein kinase/c-Jun N-terminal kinase, and p38mapk are involved in IL-10-mediated selective repression of TNF-alpha-induced activation and maturation of human peripheral blood monocyte-derived dendritic cells. J Immunol 162(7):3865–3872 (1999).PubMedGoogle Scholar
  109. 109.
    J.F. Arrighi, M. Rebsamen, F. Rousset, V. Kindler and C. Hauser. A critical role for p38 mitogen-activated protein kinase in the maturation of human blood-derived dendritic cells induced by lipopolysaccharide, TNF-alpha, and contact sensitizers. J Immunol 166(6):3837–3845 (2001).PubMedGoogle Scholar
  110. 110.
    A. Puig-Kroger, M. Relloso, O. Fernandez-Capetillo, A. Zubiaga, A. Silva, C. Bernabeu and A.L. Corbi. Extracellular signal-regulated protein kinase signaling pathway negatively regulates the phenotypic and functional maturation of monocyte-derived human dendritic cells. Blood 98(7):2175–2182 (2001).PubMedGoogle Scholar
  111. 111.
    A. Puig-Kroger, F. Sanz-Rodriguez, N. Longo, P. Sanchez-Mateos, L. Botella, J. Teixido, C. Bernabeu and A.L. Corbi. Maturation-dependent expression and function of the CD49d integrin on monocyte-derived human dendritic cells. J Immunol 165(8):4338–4345 (2000).PubMedGoogle Scholar
  112. 112.
    Y. Yanagawa, N. Iijima, K. Iwabuchi and K. Onoe. Activation of extracellular signal-related kinase by TNF-alpha controls the maturation and function of murine dendritic cells. J Leukoc Biol 71(1):125–132 (2002).PubMedGoogle Scholar
  113. 113.
    M. Rescigno, M. Martino, C.L. Sutherland, M.R. Gold and P. Ricciardi-Castagnoli. Dendritic cell survival and maturation are regulated by different signaling pathways. J Exp Med 188(11):2175–2180 (1998).PubMedGoogle Scholar
  114. 114.
    S. Yoshimura, J. Bondeson, F.M. Brennan, B.M. Foxwell and M. Feldmann. Role of NFkappaB in antigen presentation and development of regulatory T cells elucidated by treatment of dendritic cells with the proteasome inhibitor PSI. Eur J Immunol 31(6):1883–1893 (2001).PubMedGoogle Scholar
  115. 115.
    S. Yoshimura, J. Bondeson, B.M. Foxwell, F.M. Brennan and M. Feldmann. Effective antigen presentation by dendritic cells is NF-kappaB dependent: coordinate regulation of MHC, co-stimulatory molecules and cytokines. Int Immunol 13(5):675–683 (2001).PubMedGoogle Scholar
  116. 116.
    F. Ouaaz, J. Arron, Y. Zheng, Y. Choi and A.A. Beg. Dendritic cell development and survival require distinct NF-kappaB subunits. Immunity 16(2):257–270 (2002).PubMedGoogle Scholar
  117. 117.
    A.R. Pettit, K.P. MacDonald, B. O’Sullivan and R. Thomas. Differentiated dendritic cells expressing nuclear RelB are predominantly located in rheumatoid synovial tissue perivascular mononuclear cell aggregates. Arthr Rheum 43(4):791–800 (2000).Google Scholar
  118. 118.
    P.A. Baeuerle and T. Henkel. Function and activation of NF-kappa B in the immune system. Annu Rev Immunol 12(141–1790 (1994).PubMedGoogle Scholar
  119. 119.
    S. Ghosh, M.J. May and E.B. Kopp. NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. Annu Rev Immunol 16:225–260 (1998).PubMedGoogle Scholar
  120. 120.
    F.G. Wulczyn, D. Krappmann and C. Scheidereit. The NF-kappa B/Rel and I kappa B gene families: mediators of immune response and inflammation. J Mol Med 74(12):749–769 (1996).PubMedGoogle Scholar
  121. 121.
    S. Yoshimura, J. Bondeson, B.M. Foxwell, F.M. Brennan and M. Feldmann. Effective antigen presentation by dendritic cells is NF-kappaB dependent: coordinate regulation of MHC, co-stimulatory molecules and cytokines. Int Immunol 13(5):675–683 (2001).PubMedGoogle Scholar
  122. 122.
    F. Ouaaz, J. Arron, Y. Zheng, Y. Choi and A.A. Beg. Dendritic cell development and survival require distinct NF-kappaB subunits. Immunity 16(2):257–270 (2002).PubMedGoogle Scholar
  123. 123.
    D.S. Weih, Z.B. Yilmaz and F. Weih. Essential role of RelB in germinal center and marginal zone formation and proper expression of homing chemokines. J Immunol 167(4):1909–1919 (2001).PubMedGoogle Scholar
  124. 124.
    R. Valero, M.L. Baron, S. Guerin, S. Beliard, H. Lelouard, B. Kahn-Perles, B. Vialettes, C. Nguyen, J. Imbert and P. Naquet. A defective NF-kappa B/RelB pathway in autoimmune-prone New Zealand black mice is associated with inefficient expansion of thymocyte and dendritic cells. J Immunol 169(1):185–192 (2002).PubMedGoogle Scholar
  125. 125.
    B.J. O’Sullivan, K.P. MacDonald, A.R. Pettit and R. Thomas. RelB nuclear translocation regulates B cell MHC molecule, CD40 expression, and antigen-presenting cell function. Proc Natl Acad Sci USA 97(21):11421–11426 (2000).PubMedGoogle Scholar
  126. 126.
    G.J. Clark, S. Gunningham, A. Troy, S. Vuckovic and D.N. Hart. Expression of the RelB transcription factor correlates with the activation of human dendritic cells. Immunology 98(2):189–196 (1999).PubMedGoogle Scholar
  127. 127.
    F. Weih, G. Warr, H. Yang and R. Bravo. Multifocal defects in immune responses in RelB-deficient mice. J Immunol 158(11):5211–5218 (1997).PubMedGoogle Scholar
  128. 128.
    M. Neumann, H. Fries, C. Scheicher, P. Keikavoussi, A. Kolb-Maurer, E. Brocker, E. Serfling and E. Kampgen. Differential expression of Rel/NF-kappaB and octamer factors is a hallmark of the generation and maturation of dendritic cells. Blood 95(1):277–285 (2000).PubMedGoogle Scholar
  129. 129.
    D. Carrasco, R.P. Ryseck and R. Bravo. Expression of relB transcripts during lymphoid organ development: specific expression in dendritic antigen-presenting cells. Development 118(4):1221–1231 (1993).PubMedGoogle Scholar
  130. 130.
    A.R. Pettit, K.P. MacDonald, B. O’Sullivan and R. Thomas. Differentiated dendritic cells expressing nuclear RelB are predominantly located in rheumatoid synovial tissue perivascular mononuclear cell aggregates. Arthr Rheum 43(4):791–800 (2000).Google Scholar
  131. 131.
    B. Platzer, A. Jorgl, S. Taschner, B. Hocher and H. Strobl. RelB regulates human dendritic cell subset development by promoting monocyte intermediates. Blood 104(12):3655–3663 (2004).PubMedGoogle Scholar
  132. 132.
    R.P. Ryseck, P. Bull, M. Takamiya, V. Bours, U. Siebenlist, P. Dobrzanski and R. Bravo. RelB, a new Rel family transcription activator that can interact with p50-NFkappa B. Mol Cell Biol 12(2):674–684 (1992).PubMedGoogle Scholar
  133. 133.
    P. Dobrzanski, R.P. Ryseck and R. Bravo. Specific inhibition of RelB/p52 transcriptional activity by the C-terminal domain of p100. Oncogene 10(5):1003–1007 (1995).PubMedGoogle Scholar
  134. 134.
    N.J. Solan, H. Miyoshi, E.M. Carmona, G.D. Bren and C.V. Paya. RelB cellular regulation and transcriptional activity are regulated by p100. J Biol Chem 277(2):1405–1418 (2002).PubMedGoogle Scholar
  135. 135.
    K. Speirs, L. Lieberman, J. Caamano, C.A. Hunter and P. Scott. Cutting edge: NFkappa B2 is a negative regulator of dendritic cell function. J Immunol 172(2):752–756 (2004).PubMedGoogle Scholar
  136. 136.
    G. Bonizzi and M. Karin. The two NF-kappaB activation pathways and their role in innate and adaptive immunity. Trends Immunol 25(6):280–288 (2004).PubMedGoogle Scholar
  137. 137.
    G. Xiao, E.W. Harhaj and S.C. Sun. NF-kappaB-inducing kinase regulates the processing of NF-kappaB2 p100. Mol Cell 7(2):401–409 (2001).PubMedGoogle Scholar
  138. 138.
    M. Karin and Y. Ben-Neriah. Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity. Annu Rev Immunol 18:621–663 (2000).PubMedGoogle Scholar
  139. 139.
    L. Lin, G.N. DeMartino and W.C. Greene. Cotranslational biogenesis of NF-kappaB p50 by the 26S proteasome. Cell 92(6):819–828 (1998).PubMedGoogle Scholar
  140. 140.
    T. Lernbecher, B. Kistler and T. Wirth. Two distinct mechanisms contribute to the constitutive activation of RelB in lymphoid cells. Embo J 13(17):4060–4069 (1994).PubMedGoogle Scholar
  141. 141.
    D.A. Francis, R. Sen, N. Rice and T.L. Rothstein. Receptor-specific induction of NF-kappaB components in primary B cells. Int Immunol 10(3):285–293 (1998).PubMedGoogle Scholar
  142. 142.
    B. Kistler, A. Rolink, R. Marienfeld, M. Neumann and T. Wirth. Induction of nuclear factor-kappa B during primary B cell differentiation. J Immunol 160(5):2308–2317 (1998).PubMedGoogle Scholar
  143. 143.
    M. Suhasini, C.D. Reddy, E.P. Reddy, J.A. DiDonato and R.B. Pilz. cAMP-induced NF-kappaB (p50/relB) binding to a c-myb intronic enhancer correlates with c-myb up-regulation and inhibition of erythroleukemia cell differentiation. Oncogene 15(15):1859–1870 (1997).PubMedGoogle Scholar
  144. 144.
    F. Rossi, M. McNagny, G. Smith, J. Frampton and T. Graf. Lineage commitment of transformed haematopoietic progenitors is determined by the level of PKC activity. Embo J 15(8):1894–1901 (1996).PubMedGoogle Scholar
  145. 145.
    S. Glennie, I. Soeiro, P.J. Dyson, E.W. Lam and F. Dazzi. Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells. Blood 105(7):2821–2827 (2005).PubMedGoogle Scholar
  146. 146.
    B. Verdoodt, T. Blazek, P. Rauch, G. Schuler, A. Steinkasserer, M.B. Lutz and J.O. Funk. The cyclin-dependent kinase inhibitors p27Kip1 and p21Cip1 are not essential in T cell anergy. Eur J Immunol 33(11):3154–3163 (2003).PubMedGoogle Scholar
  147. 147.
    A.D. Wells, M.C. Walsh, J.A. Bluestone and L.A. Turka. Signaling through CD28 and CTLA-4 controls two distinct forms of T cell anergy. J Clin Invest 108(6):895–903 (2001).PubMedGoogle Scholar
  148. 148.
    J. Sun, M. Alison Stalls, K.L. Thompson and N. Fisher Van Houten. Cell cycle block in anergic T cells during tolerance induction. Cell Immunol 225(1):33–41 (2003).PubMedGoogle Scholar
  149. 149.
    D.I. Gabrilovich, H.L. Chen, K.R. Girgis, H.T. Cunningham, G.M. Meny, S. Nadaf, D. Kavanaugh and D.P. Carbone. Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nat Med 2(10):1096–1103 (1996).PubMedGoogle Scholar
  150. 150.
    T. Oyama, S. Ran, T. Ishida, S. Nadaf, L. Kerr, D.P. Carbone and D.I. Gabrilovich. Vascular endothelial growth factor affects dendritic cell maturation through the inhibition of nuclear factor-kappa B activation in hemopoietic progenitor cells. J Immunol 160(3):1224–1232 (1998).PubMedGoogle Scholar
  151. 151.
    N. Boissel, P. Rousselot, E. Raffoux, J.M. Cayuela, O. Maarek, D. Charron, L. Degos, H. Dombret, A. Toubert and D. Rea. Defective blood dendritic cells in chronic myeloid leukemia correlate with high plasmatic VEGF and are not normalized by imatinib mesylate. Leukemia 18(10):1656–1661 (2004).PubMedGoogle Scholar
  152. 152.
    A. Agrawal, J. Lingappa, S.H. Leppla, S. Agrawal, A. Jabbar, C. Quinn and B. Pulendran. Impairment of dendritic cells and adaptive immunity by anthrax lethal toxin. Nature 424(6946):329–334 (2003).PubMedGoogle Scholar
  153. 153.
    S. Mahanty, K. Hutchinson, S. Agarwal, M. McRae, P.E. Rollin and B. Pulendran. Cutting edge: impairment of dendritic cells and adaptive immunity by Ebola and Lassa viruses. J Immunol 170(6):2797–2801 (2003).PubMedGoogle Scholar
  154. 154.
    G. Denecker, W. Declercq, C.A. Geuijen, A. Boland, R. Benabdillah, M. van Gurp, M.P. Sory, P. Vandenabeele and G.R. Cornelis. Yersinia enterocolitica YopPinduced apoptosis of macrophages involves the apoptotic signaling cascade upstream of bid. J Biol Chem 276(23):19706–19714 (2001).PubMedGoogle Scholar
  155. 155.
    C.J. Hueck. Type III protein secretion systems in bacterial pathogens of animals and plants. Microbiol Mol Biol Rev 62(2):379–433 (1998).PubMedGoogle Scholar
  156. 156.
    L.E. Palmer, A.R. Pancetti, S. Greenberg and J.B. Bliska. YopJ of Yersinia spp. Is sufficient to cause downregulation of multiple mitogen-activated protein kinases in eukaryotic cells. Infect Immun 67(2):708–716 (1999).PubMedGoogle Scholar
  157. 157.
    I. Sorg, U.M. Goehring, K. Aktories and G. Schmidt. Recombinant Yersinia YopT leads to uncoupling of RhoA-effector interaction. Infect Immun 69(12):7535–7543 (2001).PubMedGoogle Scholar
  158. 158.
    M. Iriarte and G.R. Cornelis. YopT, a new Yersinia Yop effector protein, affects the cytoskeleton of host cells. Mol Microbiol 29(3):915–929 (1998).PubMedGoogle Scholar
  159. 159.
    R. Rosqvist, A. Forsberg and H. Wolf-Watz. Intracellular targeting of the Yersinia YopE cytotoxin in mammalian cells induces actin microfilament disruption. Infect Immun 59(12):4562–4569 (1991).PubMedGoogle Scholar
  160. 160.
    K. Schesser, A.K. Spiik, J.M. Dukuzumuremyi, M.F. Neurath, S. Pettersson and H. Wolf-Watz. The yopJ locus is required for Yersinia-mediated inhibition of NFkappaB activation and cytokine expression: YopJ contains a eukaryotic SH2-like domain that is essential for its repressive activity. Mol Microbiol 28(6):1067–1079 (1998).PubMedGoogle Scholar
  161. 161.
    G.R. Cornelis, A. Boland, A.P. Boyd, C. Geuijen, M. Iriarte, C. Neyt, M.P. Sory and I. Stainier. The virulence plasmid of Yersinia, an antihost genome. Microbiol Mol Biol Rev 62(4):1315–1352 (1998).PubMedGoogle Scholar
  162. 162.
    M. Aepfelbacher, R. Zumbihl, K. Ruckdeschel, C.A. Jacobi, C. Barz and J. Heesemann. The tranquilizing injection of Yersinia proteins: a pathogen’s strategy to resist host defense. Biol Chem 380(7–8):795–802 (1999).PubMedGoogle Scholar
  163. 163.
    K. Ruckdeschel, S. Harb, A. Roggenkamp, M. Hornef, R. Zumbihl, S. Kohler, J. Heesemann and B. Rouot. Yersinia enterocolitica impairs activation of transcription factor NF-kappaB: involvement in the induction of programmed cell death and in the suppression of the macrophage tumor necrosis factor alpha production. J Exp Med 187(7):1069–1079 (1998).PubMedGoogle Scholar
  164. 164.
    K. Orth, Z. Xu, M.B. Mudgett, Z.Q. Bao, L.E. Palmer, J.B. Bliska, W.F. Mangel, B. Staskawicz and J.E. Dixon. Disruption of signaling by Yersinia effector YopJ, a ubiquitin-like protein protease. Science 290(5496):1594–1597 (2000).PubMedGoogle Scholar
  165. 165.
    K. Orth, L.E. Palmer, Z.Q. Bao, S. Stewart, A.E. Rudolph, J.B. Bliska and J.E. Dixon. Inhibition of the mitogen-activated protein kinase kinase superfamily by a Yersinia effector. Science 285(5435):1920–1923 (1999).PubMedGoogle Scholar
  166. 166.
    S.E. Erfurth, S. Grobner, U. Kramer, D.S. Gunst, I. Soldanova, M. Schaller, I.B. Autenrieth and S. Borgmann. Yersinia enterocolitica induces apoptosis and inhibits surface molecule expression and cytokine production in murine dendritic cells. Infect Immun 72(12):7045–7054 (2004).PubMedGoogle Scholar
  167. 167.
    M. Schoppet, A. Bubert and H.I. Huppertz. Dendritic cell function is perturbed by Yersinia enterocolitica infection in vitro. Clin Exp Immunol 122(3):316–323 (2000).PubMedGoogle Scholar
  168. 168.
    K. Trulzsch, G. Geginat, T. Sporleder, K. Ruckdeschel, R. Hoffmann, J. Heesemann and H. Russmann. Yersinia outer protein P inhibits CD8 T cell priming in the mouse infection model. J Immunol 174(7):4244–4251 (2005).PubMedGoogle Scholar
  169. 169.
    M.M. Marketon, R.W. Depaolo, K.L. Debord, B. Jabri and O. Schneewind. Plague bacteria target immune cells during infection. Science 309(5741):1739–1741 (2005).PubMedGoogle Scholar
  170. 170.
    B.A. Chromy: J. Perkins, J.L. Heidbrink, A.D. Gonzales, G.A. Murphy, J.P. Fitch and S.L. McCutchen-Maloney. Proteomic characterization of host response to Yersinia pestis and near neighbors. Biochem Biophys Res Commun 320(2):474–479 (2004).PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Inna Lindner
    • 1
  • Pedro J. Cejas
    • 1
  • Louise M. Carlson
    • 1
  • Julie Torruellas
    • 1
  • Gregory V. Plano
    • 1
  • Kelvin P. Lee
    • 1
  1. 1.University of Miami Miller School of MedicineMiamiUSA

Personalised recommendations