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Departments of
*
Cell Biology and Histology and
Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
Department of Infectious Disease and Immunology, Okinawa-Asia Research Center of Medical Sciences, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan; and
Department of Parasitology, Medical Center Leiden, Leiden, The Netherlands
Upon microbial infection, specific Th1 or Th2 responses develop depending on the type of microbe. Here, we demonstrate that different microbial compounds polarize the maturation of human myeloid dendritic cells (DCs) into stably committed Th1 cell-promoting (DC1) or Th2 cell-promoting (DC2) effector DCs that polarize Th cells via different mechanisms. Protein extract derived from the helminth Schistosoma mansoni induced the development of DC2s that promote the development of Th2 cells via the enhanced expression of OX40 ligand. Likewise, toxin from the extracellular bacterium Vibrio cholerae induced development of DC2s as well, however, via an OX40 ligand-independent, still unknown mechanism. In contrast, toxin from the intracellular bacterium Bordetella pertussis induced the development of DC1s with enhanced IL-12 production, which promotes a Th1 cell development. Poly(I:C) (dsRNA, mimic for virus) induced the development of extremely potent Th1-inducing DC1, surprisingly, without an enhanced IL-12 production. The obtained DC1s and DC2s are genuine effector cells that stably express Th cell-polarizing factors and are unresponsive to further modulation. The data suggest that the molecular basis of Th1/Th2 polarization via DCs is unexpectedly diverse and is adapted to the nature of the microbial compounds.
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A. D. Straw, A. S. MacDonald, E. Y. Denkers, and E. J. Pearce CD154 Plays a Central Role in Regulating Dendritic Cell Activation During Infections That Induce Th1 or Th2 Responses J. Immunol., January 15, 2003; 170(2): 727 - 734. [Abstract] [Full Text] [PDF]
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A. Boonstra, C. Asselin-Paturel, M. Gilliet, C. Crain, G. Trinchieri, Y.-J. Liu, and A. O'Garra Flexibility of Mouse Classical and Plasmacytoid-derived Dendritic Cells in Directing T Helper Type 1 and 2 Cell Development: Dependency on Antigen Dose and Differential Toll-like Receptor Ligation J. Exp. Med., January 6, 2003; 197(1): 101 - 109. [Abstract] [Full Text] [PDF]
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D. Sewell, Z. Qing, E. Reinke, D. Elliot, J. Weinstock, M. Sandor, and Z. Fabry Immunomodulation of experimental autoimmune encephalomyelitis by helminth ova immunization Int. Immunol., January 1, 2003; 15(1): 59 - 69. [Abstract] [Full Text] [PDF]
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 D. van der Kleij, E. Latz, J. F. H. M. Brouwers, Y. C. M. Kruize, M. Schmitz, E. A. Kurt-Jones, T. Espevik, E. C. de Jong, M. L. Kapsenberg, D. T. Golenbock, et al. A Novel Host-Parasite Lipid Cross-talk. SCHISTOSOMAL LYSO-PHOSPHATIDYLSERINE ACTIVATES TOLL-LIKE RECEPTOR 2 AND AFFECTS IMMUNE POLARIZATION J. Biol. Chem., December 6, 2002; 277(50): 48122 - 48129. [Abstract] [Full Text] [PDF]
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A. D. Edwards, S. P. Manickasingham, R. Sporri, S. S. Diebold, O. Schulz, A. Sher, T. Kaisho, S. Akira, and C. Reis e Sousa Microbial Recognition Via Toll-Like Receptor-Dependent and -Independent Pathways Determines the Cytokine Response of Murine Dendritic Cell Subsets to CD40 Triggering J. Immunol., October 1, 2002; 169(7): 3652 - 3660. [Abstract] [Full Text] [PDF]
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T. Tatsumi, L. S. Kierstead, E. Ranieri, L. Gesualdo, F. P. Schena, J. H. Finke, R. M. Bukowski, J. Mueller-Berghaus, J. M. Kirkwood, W. W. Kwok, et al. Disease-associated Bias in T Helper Type 1 (Th1)/Th2 CD4+ T Cell Responses Against MAGE-6 in HLA-DRB10401+ Patients With Renal Cell Carcinoma or Melanoma J. Exp. Med., September 2, 2002; 196(5): 619 - 628. [Abstract] [Full Text] [PDF]
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R. W. Sanders, E. C. de Jong, C. E. Baldwin, J. H. N. Schuitemaker, M. L. Kapsenberg, and B. Berkhout Differential Transmission of Human Immunodeficiency Virus Type 1 by Distinct Subsets of Effector Dendritic Cells J. Virol., June 27, 2002; 76(15): 7812 - 7821. [Abstract] [Full Text] [PDF]
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S. Ebner, S. Hofer, V. A. Nguyen, C. Furhapter, M. Herold, P. Fritsch, C. Heufler, and N. Romani A Novel Role for IL-3: Human Monocytes Cultured in the Presence of IL-3 and IL-4 Differentiate into Dendritic Cells That Produce Less IL-12 and Shift Th Cell Responses Toward a Th2 Cytokine Pattern J. Immunol., June 15, 2002; 168(12): 6199 - 6207. [Abstract] [Full Text] [PDF]
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 M. Yazdanbakhsh, P. G. Kremsner, and R. van Ree Allergy, Parasites, and the Hygiene Hypothesis Science, April 19, 2002; 296(5567): 490 - 494. [Abstract] [Full Text] [PDF]
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