Plasticity of Dendritic Cell Transcriptional Responses to Antigen: Functional States of Dendritic Cells

  • Paul Kellam
  • Antonia Kwan


The vertebrate immune system protects the host from harmful encounters with pathogenic microorganisms and other dangerous components of the environment. To do this the immune system must gather information about the ‘nonself’ pathogens and by processing this information, initiate an appropriate immunological response. The immune system represents an example of emergent behavior from a complex, multifactorial, adaptive system. To understand emergent behavior we need to know the systems components and the rules that govern the system. To identify the components, immunology research has catalogued and characterized probably all major cell types involved in the innate and adaptive immune response. In the postgenomic world, we are now able to further characterize global changes in cellular gene expression and thereby identify and infer changes in the functional state of the cells. Together this should allow modeling of immune system function. Dendritic cells orchestrate the host immune response. By identifying a pathogen and processing this information through a coordinated differentiation program, phenotypic changes effected in dentritic cells allow appropriate information to be conveyed to the adaptive arm of the immune system, thereby shaping downstream immunological responses. Transcriptional profiling of human and mouse dendritic cell responses to different antigens have demonstrated this functional plasticity. Understanding the regulation of these dendritic cell differentiation states will contribute to computational models of the immune system, and our understanding of the parameters that affect the immune system response to infection.


Dendritic Cell Gene Expression Program Plasmacytoid Dendritic Cell Switch Threshold Functional Plasticity 
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.


  1. Akira, S., and Takeda, K. (2004) Toll-like receptor signalling. Nat. Rev. Immunol. 4:499-511.PubMedCrossRefGoogle Scholar
  2. Allan, M.J., Callard, R., Stark, J., and Yates, A. (2004) Comparing antigen-independent mechanisms of T cell regulation. J. Theor. Biol. 228:81-95.PubMedCrossRefGoogle Scholar
  3. Amsen, D., Blander, J.M., Lee, G.R., Tanigaki, K., Honjo, T., and Flavell, R.A. (2004) Instruction of distinct CD4 T helper cell fates by different notch ligands on antigen-presenting cells. Cell 117:515-526.PubMedCrossRefGoogle Scholar
  4. Andrews, D.M., Andoniou, C.E., Granucci, F., Ricciardi-Castagnoli, P., and Degli-Esposti, M.A. (2001) Infection of dendritic cells by murine cytomegalovirus induces functional paralysis. Nat. Immunol. 2:1077-1084.PubMedCrossRefGoogle Scholar
  5. Bar-Joseph, Z. (2004) Analyzing time series gene expression data. Bioinformatics 20:2493-2503.PubMedCrossRefGoogle Scholar
  6. Bleharski, J.R., Niazi, K.R., Sieling, P.A., Cheng, G., and Modlin, R.L. (2001) Signaling lymphocytic activation molecule is expressed on CD40 ligand-activated dendritic cells and directly augments production of inflammatory cytokines. J. Immunol. 167:3174-3181.PubMedGoogle Scholar
  7. Bouwmeester, T., Bauch, A., Ruffner, H., Angrand, P.O., Bergamini, G., Croughton, K., Cruciat, C., Eberhard, D., Gagneur, J., Ghidelli, S., Hopf, C., Huhse, B., Mangano, R., Michon, A.M., Schirle, M., Schlegl, J., Schwab, M., Stein, M.A., Bauer, A., Casari, G., Drewes, G., Gavin, A.C., Jackson, D.B., Joberty, G., Neubauer, G., Rick, J., Kuster, B., and Superti-Furga, G. (2004) A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. Nat. Cell Biol. 6:97-105.PubMedCrossRefGoogle Scholar
  8. Callard, R., George, A.J., and Stark, J. (1999) Cytokines, chaos, and complexity. Immunity 11:507-513.PubMedCrossRefGoogle Scholar
  9. Chaussabel, D., Semnani, R.T., McDowell, M.A., Sacks, D., Sher, A., and Nutman, T.B. (2003) Unique gene expression profiles of human macrophages and dendritic cells to phylogenetically distinct parasites. Blood 102:672-681.PubMedCrossRefGoogle Scholar
  10. Cho, K.H., Shin, S.Y., Lee, H.W., and Wolkenhauer, O. (2003) Investigations into the analysis and modeling of the TNF alpha-mediated NF-kappa B-signaling pathway. Genome Res. 13:2413-2422.PubMedCrossRefGoogle Scholar
  11. Gavin, A.C., Bosche, M., Krause, R., Grandi, P., Marzioch, M., Bauer, A., Schultz, J., Rick, J.M., Michon, A.M., Cruciat, C.M., Remor, M., Hofert, C., Brajenovic, M., Ruffner, H., Merino, A., Klein, K., Hudak, M., Dickson, D., Rudi, T., Gnau, V., Bauch, A., Bastuck, S., Huhse, B., Leutwein, C., Heurtier, M.A., Copley, R.R., Edelmann, A., Querfurth, E., Rybin, V., Drewes, G., Raida, M., Bouwmeester, T., Bork, P., Seraphin, B., Kuster, B., Neubauer, G., and Superti-Furga, G. (2002) Functional organization of the yeast proteome by systematic analysis of protein complexes. Nature 415:141-147.PubMedCrossRefGoogle Scholar
  12. Granucci, F., Vizzardelli, C., Virzi, E., Rescigno, M., and Ricciardi-Castagnoli, P. (2001a) Transcriptional reprogramming of dendritic cells by differentiation stimuli. Eur. J. Immunol. 31:2539-2546.CrossRefGoogle Scholar
  13. Granucci, F., Vizzardelli, C., Pavelka, N., Feau, S., Persico, M., Virzi, E., Rescigno, M., Moro, G., and Ricciardi-Castagnoli, P. (2001b) Inducible IL-2 production by dendritic cells revealed by global gene expression analysis. Nat. Immunol. 2:882-888.CrossRefGoogle Scholar
  14. Hoebe, K., Janssen, E., and Beutler, B. (2004) The interface between innate and adaptive immunity. Nat. Immunol. 5:971-974.PubMedCrossRefGoogle Scholar
  15. Huang, Q., Liu, D., Majewski, P., Schulte, L.C., Korn, J.M., Young, R.A., Lander, E.S., and Hacohen, N. (2001) The plasticity of dendritic cell responses to pathogens and their components. Science 294:870-875.PubMedCrossRefGoogle Scholar
  16. Iwasaki, A., and Medzhitov, R. (2004). Toll-like receptor control of the adaptive immune responses. Nat. Immunol. 5:987-995.PubMedCrossRefGoogle Scholar
  17. Izmailova, E., Bertley, F.M., Huang, Q., Makori, N., Miller, C.J., Young, R.A., and Aldovini, A. (2003) HIV-1 Tat reprograms immature dendritic cells to express chemoattractants for activated T cells and macrophages. Nat. Med. 9:191-197.PubMedCrossRefGoogle Scholar
  18. Jego, G., Palucka, A.K., Blanck, J.P., Chalouni, C., Pascual, V., and Banchereau, J. (2003) Plasmacytoid dendritic cells induce plasma cell differentiation through type I interferon and interleukin 6. Immunity 19:225-234.PubMedCrossRefGoogle Scholar
  19. Kellam, P., Liu, X., Martin, N., Orengo, C., Swift, S., and Tucker, A. (2001) A framework for modelling short, high-dimensional multivariate time series. Preliminary results in virus gene expression data analysis. In: Advances in Intelligent Data Analysis: 4th International Conference, IDA 2001. Lecture Notes in Computer Science 2189. Springer, Berlin, pp. 218-227.Google Scholar
  20. Kitano, H. (2004) Biological robustness. Nat. Rev. Genet. 5:826-837.PubMedCrossRefGoogle Scholar
  21. Langenkamp, A., Messi, M., Lanzavecchia, A., and Sallusto, F. (2000) Kinetics of dendritic cell activation: Impact on priming of TH1, TH2 and nonpolarized T cells. Nat. Immunol. 1:311-316.PubMedCrossRefGoogle Scholar
  22. Maekawa, Y., Tsukumo, S., Chiba, S., Hirai, H., Hayashi, Y., Okada, H., Kishihara, K., and Yasutomo, K. (2003) Delta1-Notch3 interactions bias the functional differentiation of activated CD4+ T cells. Immunity 19:549-559.PubMedCrossRefGoogle Scholar
  23. Mempel, T.R., Henrickson, S.E., and Von Andrian, U.H. (2004) T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases. Nature 427:154-159.PubMedCrossRefGoogle Scholar
  24. O’Garra, A. (1998) Cytokines induce the development of functionally heterogeneous T helper cell subsets. Immunity 8:275-283.PubMedCrossRefGoogle Scholar
  25. Poeck, H., Wagner, M., Battiany, J., Rothenfusser, S., Wellisch, D., Hornung, V., Jahrsdorfer, B., Giese, T., Endres, S., and Hartmann, G. (2004). Plasmacytoid dendritic cells, antigen, and CpG-C license human B cells for plasma cell differentiation and immunoglobulin production in the absence of T-cell help. Blood 103:3058-3064.PubMedCrossRefGoogle Scholar
  26. Ryan, C.A., Gildea, L.A., Hulette, B.C., Dearman, R.J., Kimber, I., and Gerberick, G.F. (2004) Gene expression changes in peripheral blood-derived dendritic cells following exposure to a contact allergen. Toxicol. Lett. 150:301-316.PubMedCrossRefGoogle Scholar
  27. Shigematsu, H., Reizis, B., Iwasaki, H., Mizuno, S., Hu, D., Traver, D., Leder, P., Sakaguchi, N., Akashi, K. (2004). Plasmacytoid dendritic cells activate lymphoid-specific genetic programs irrespective of their cellular origin. Immunity 21:43-53.PubMedCrossRefGoogle Scholar
  28. Shortman, K., and Liu, Y.J. (2002) Mouse and human dendritic cell subtypes. Nat. Rev. Immunol. 2:151-161.Google Scholar
  29. Suciu-Foca Cortesini, N., Piazza, F., Ho, E., Ciubotariu, R., LeMaoult, J., Dalla-Favera, R., and Cortesini, R. (2001) Distinct mRNA microarray profiles of tolerogenic dendritic cells. Hum. Immunol. 62:1065-1072.PubMedCrossRefGoogle Scholar
  30. Xie, H., Ye, M., Feng, R., and Graf, T. (2004). Stepwise reprogramming of B cells into macrophages. Cell 117:663-676.Google Scholar
  31. Yan, W., Lee, H., Yi, E.C., Reiss, D., Shannon, P., Kwieciszewski, B.K., Coito, C., Li, X.J., Keller, A., Eng. J., Galitski, T., Goodlett, D.R., Aebersold, R., and Katze, M.G. (2004) System-based proteomic analysis of the interferon response in human liver cells. Genome Biol. 5:R54.PubMedCrossRefGoogle Scholar
  32. Yates, A., Callard, R., and Stark, J. (2004) Combining cytokine signalling with T-bet and GATA-3 regulation in Th1 and Th2 differentiation: A model for cellular decision-making. J. Theor. Biol. 231:181-196.PubMedCrossRefGoogle Scholar
  33. Zhou, X., Kao, M.C., and Wong, W.H. (2002) Transitive functional annotation by shortest-path analysis of gene expression data. Proc. Natl. Acad. Sci. USA 99:12783-12788.Google Scholar
  34. Zuniga, E.I., McGavern, D.B., Pruneda-Paz, J.L., Teng, C., and Oldstone, M.B. (2004) Bone marrow plasmacytoid dendritic cells can differentiate into myeloid dendritic cells upon virus infection. Nat. Immunol. 5:1227-1234.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Paul Kellam
    • 1
  • Antonia Kwan
    • 1
  1. 1.Department of InfectionUniversity College LondonLondonUK

Personalised recommendations