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*
Institute for Medical Microbiology, Immunology and Hygiene, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany; and
Institute for Experimental Hematology, GSF National Research Center for Environment and Health, Munich, Germany
Human plasmacytoid precursor dendritic cells (ppDC) are a major
source of type I IFN upon exposure to virus and bacteria, yet the
stimulus causing their maturation into DCs is unknown. After PBMC
activation with immunostimulatory bacterial DNA sequences
(CpG-DNA) we found that ppDC are the primary source of IFN-
. In
fact, either CpG-DNA or dsRNA (poly(I:C)) induced IFN- from purified
ppDC. Surprisingly, only CpG-DNA triggered purified ppDC survival,
maturation, and production of TNF, GM-CSF, IL-6, and IL-8, but not
IL-10 or IL-12. Known DC activators such as CD40 ligation triggered
ppDC maturation, but only IL-8 production, while bacterial LPS was
negative for all activation criteria. An additional finding was that
only CpG-DNA could counteract IL-4-induced apoptosis in ppDC.
Therefore, CpG-DNA represents a pathogen-associated molecular pattern
for ppDC. In contrast to these finding, CpG-DNA, like LPS, caused TNF,
IL-6, and IL-12 release from PBMC and purified monocytes; however,
differentiation of monocytes into DCs with GM-CSF and IL-4 unexpectedly
resulted in refractoriness to CpG-DNA, but not LPS. Taken together,
these results suggest that within a DC subset a multiplicity of
responses can be generated by distinct environmental stimuli and that
responses to a given stimulus may be dissimilar between DC
subsets.
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M.-C. Rissoan, T. Duhen, J.-M. Bridon, N. Bendriss-Vermare, C. Peronne, B. d. S. Vis, F. Briere, and E. E. M. Bates Subtractive hybridization reveals the expression of immunoglobulinlike transcript 7, Eph-B1, granzyme B, and 3 novel transcripts in human plasmacytoid dendritic cells Blood, October 16, 2002; 100(9): 3295 - 3303. [Abstract] [Full Text] [PDF]
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K. Heckelsmiller, K. Rall, S. Beck, A. Schlamp, J. Seiderer, B. Jahrsdorfer, A. Krug, S. Rothenfusser, S. Endres, and G. Hartmann Peritumoral CpG DNA Elicits a Coordinated Response of CD8 T Cells and Innate Effectors to Cure Established Tumors in a Murine Colon Carcinoma Model J. Immunol., October 1, 2002; 169(7): 3892 - 3899. [Abstract] [Full Text] [PDF]
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H. T. Ichikawa, L. P. Williams, and B. M. Segal Activation of APCs Through CD40 or Toll-Like Receptor 9 Overcomes Tolerance and Precipitates Autoimmune Disease J. Immunol., September 1, 2002; 169(5): 2781 - 2787. [Abstract] [Full Text] [PDF]
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M. Gierynska, U. Kumaraguru, S.-K. Eo, S. Lee, A. Krieg, and B. T. Rouse Induction of CD8 T-Cell-Specific Systemic and Mucosal Immunity against Herpes Simplex Virus with CpG-Peptide Complexes J. Virol., June 5, 2002; 76(13): 6568 - 6576. [Abstract] [Full Text] [PDF]
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T. Ito, R. Amakawa, T. Kaisho, H. Hemmi, K. Tajima, K. Uehira, Y. Ozaki, H. Tomizawa, S. Akira, and S. Fukuhara Interferon-{alpha} and Interleukin-12 Are Induced Differentially by Toll-like Receptor 7 Ligands in Human Blood Dendritic Cell Subsets J. Exp. Med., June 3, 2002; 195(11): 1507 - 1512. [Abstract] [Full Text] [PDF]
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V. Hornung, S. Rothenfusser, S. Britsch, A. Krug, B. Jahrsdorfer, T. Giese, S. Endres, and G. Hartmann Quantitative Expression of Toll-Like Receptor 1-10 mRNA in Cellular Subsets of Human Peripheral Blood Mononuclear Cells and Sensitivity to CpG Oligodeoxynucleotides J. Immunol., May 1, 2002; 168(9): 4531 - 4537. [Abstract] [Full Text] [PDF]
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W. Barchet, M. Cella, B. Odermatt, C. Asselin-Paturel, M. Colonna, and U. Kalinke Virus-induced Interferon {alpha} Production by a Dendritic Cell Subset in the Absence of Feedback Signaling In Vivo J. Exp. Med., February 19, 2002; 195(4): 507 - 516. [Abstract] [Full Text] [PDF]
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I. Miconnet, S. Koenig, D. Speiser, A. Krieg, P. Guillaume, J.-C. Cerottini, and P. Romero CpG Are Efficient Adjuvants for Specific CTL Induction Against Tumor Antigen-Derived Peptide J. Immunol., February 1, 2002; 168(3): 1212 - 1218. [Abstract] [Full Text] [PDF]
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 M. F. Lipscomb and B. J. Masten Dendritic Cells: Immune Regulators in Health and Disease Physiol Rev, January 1, 2002; 82(1): 97 - 130. [Abstract] [Full Text] [PDF]
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A. Dzionek, Y. Sohma, J. Nagafune, M. Cella, M. Colonna, F. Facchetti, G. Gunther, I. Johnston, A. Lanzavecchia, T. Nagasaka, et al. BDCA-2, a Novel Plasmacytoid Dendritic Cell-specific Type II C-type Lectin, Mediates Antigen Capture and Is a Potent Inhibitor of Interferon {alpha}/{beta} Induction J. Exp. Med., December 17, 2001; 194(12): 1823 - 1834. [Abstract] [Full Text] [PDF]
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H. Nakano, M. Yanagita, and M. D. Gunn Cd11c+B220+Gr-1+ Cells in Mouse Lymph Nodes and Spleen Display Characteristics of Plasmacytoid Dendritic Cells J. Exp. Med., October 15, 2001; 194(8): 1171 - 1178. [Abstract] [Full Text] [PDF]
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N. Kadowaki, S. Ho, S. Antonenko, R. de Waal Malefyt, R. A. Kastelein, F. Bazan, and Y.-J. Liu Subsets of Human Dendritic Cell Precursors Express Different Toll-like Receptors and Respond to Different Microbial Antigens J. Exp. Med., September 17, 2001; 194(6): 863 - 870. [Abstract] [Full Text] [PDF]
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M. Gilliet, A. Boonstra, C. Paturel, S. Antonenko, X.-L. Xu, G. Trinchieri, A. O'Garra, and Y.-J. Liu The Development of Murine Plasmacytoid Dendritic Cell Precursors Is Differentially Regulated by FLT3-ligand and Granulocyte/Macrophage Colony-Stimulating Factor J. Exp. Med., April 1, 2002; 195(7): 953 - 958. [Abstract] [Full Text] [PDF]
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