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* Immunobiology Laboratory, Cancer Research U.K., London Research Institute, London, United Kingdom;
Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita City, Osaka, Japan; and
RIKEN Research Center for Allergy and Immunology, Yokohama City, Japan
Dendritic cells (DC) can produce Th-polarizing cytokines and direct
the class of the adaptive immune response. Microbial stimuli,
cytokines, chemokines, and T cell-derived signals all have been shown
to trigger cytokine synthesis by DC, but it remains unclear whether
these signals are functionally equivalent and whether they determine
the nature of the cytokine produced or simply initiate a preprogrammed
pattern of cytokine production, which may be DC subtype specific. Here,
we demonstrate that microbial and T cell-derived stimuli can synergize
to induce production of high levels of IL-12 p70 or IL-10 by individual
murine DC subsets but that the choice of cytokine is dictated by the
microbial pattern recognition receptor engaged. We show that bacterial
components such as CpG-containing DNA or extracts from
Mycobacterium tuberculosis predispose
CD8
+ and CD8-CD4- DC to
make IL-12 p70. In contrast, exposure of CD8+,
CD4+ and CD8-CD4- DC to
heat-killed yeasts leads to production of IL-10. In both cases,
secretion of high levels of cytokine requires a second signal from T
cells, which can be replaced by CD40 ligand. Consistent with their
differential effects on cytokine production, extracts from M.
tuberculosis promote IL-12 production primarily via Toll-like
receptor 2 and an MyD88-dependent pathway, whereas heat-killed yeasts
activate DC via a Toll-like receptor 2-, MyD88-, and Toll/IL-1R domain
containing protein-independent pathway. These results show that
T cell feedback amplifies innate signals for cytokine production by DC
and suggest that pattern recognition rather than ontogeny determines
the production of cytokines by individual DC
subsets.
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R. Zhang, C. J. Fichtenbaum, D. A. Hildeman, J. D. Lifson, and C. Chougnet CD40 Ligand Dysregulation in HIV Infection: HIV Glycoprotein 120 Inhibits Signaling Cascades Upstream of CD40 Ligand Transcription J. Immunol., February 15, 2004; 172(4): 2678 - 2686. [Abstract] [Full Text] [PDF]
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J. A. Perry, A. Rush, R. J. Wilson, C. S. Olver, and A. C. Avery Dendritic Cells from Malaria-Infected Mice Are Fully Functional APC J. Immunol., January 1, 2004; 172(1): 475 - 482. [Abstract] [Full Text] [PDF]
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R. Sporri and C. Reis e Sousa Newly Activated T Cells Promote Maturation of Bystander Dendritic Cells but Not IL-12 Production J. Immunol., December 15, 2003; 171(12): 6406 - 6413. [Abstract] [Full Text] [PDF]
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C. Asselin-Paturel, G. Brizard, J.-J. Pin, F. Briere, and G. Trinchieri Mouse Strain Differences in Plasmacytoid Dendritic Cell Frequency and Function Revealed by a Novel Monoclonal Antibody J. Immunol., December 15, 2003; 171(12): 6466 - 6477. [Abstract] [Full Text] [PDF]
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T. Darville, J. M. O'Neill, C. W. Andrews Jr., U. M. Nagarajan, L. Stahl, and D. M. Ojcius Toll-Like Receptor-2, but Not Toll-Like Receptor-4, Is Essential for Development of Oviduct Pathology in Chlamydial Genital Tract Infection J. Immunol., December 1, 2003; 171(11): 6187 - 6197. [Abstract] [Full Text] [PDF]
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C. Chougnet Role of CD40 Ligand dysregulation in HIV-associated dysfunction of antigen-presenting cells J. Leukoc. Biol., November 1, 2003; 74(5): 702 - 709. [Abstract] [Full Text] [PDF]
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H. Kuipers, D. Hijdra, V. C. de Vries, H. Hammad, J.-B. Prins, A. J. Coyle, H. C. Hoogsteden, and B. N. Lambrecht Lipopolysaccharide-Induced Suppression of Airway Th2 Responses Does Not Require IL-12 Production by Dendritic Cells J. Immunol., October 1, 2003; 171(7): 3645 - 3654. [Abstract] [Full Text] [PDF]
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C.-M. Sun, L. Fiette, M. Tanguy, C. Leclerc, and R. Lo-Man Ontogeny and innate properties of neonatal dendritic cells Blood, July 15, 2003; 102(2): 585 - 591. [Abstract] [Full Text] [PDF]
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A. D. Edwards, D. Chaussabel, S. Tomlinson, O. Schulz, A. Sher, and C. Reis e Sousa Relationships Among Murine CD11chigh Dendritic Cell Subsets as Revealed by Baseline Gene Expression Patterns J. Immunol., July 1, 2003; 171(1): 47 - 60. [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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