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CUTTING EDGE |
* Emory Vaccine Center, Atlanta, GA 30329;
Departments of Pathology and Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77550;
Department of Pathology, Emory University, Atlanta, GA 30322;
Department of Cell Biology, Harvard Medical School, Boston, MA 02115; and
¶ Department of Periodontology and Oral Biology, Boston University School of Dental Medicine, Boston, MA 02215
Dendritic cells (DCs) are pivotal in determining the class of an adaptive immune response. However, the molecular mechanisms within DCs that determine this decision-making process are unknown. Here, we demonstrate that distinct Toll-like receptor (TLR) ligands instruct human DCs to induce distinct Th cell responses by differentially modulating mitogen-activated protein kinase signaling. Thus, Escherichia coli LPS and flagellin, which trigger TLR4 and TLR5, respectively, instruct DCs to stimulate Th1 responses via IL-12p70 production, which depends on the phosphorylation of p38 and c-Jun N-terminal kinase 1/2. In contrast, the TLR2 agonist, Pam3cys, and the Th2 stimulus, schistosome egg Ags: 1) barely induce IL-12p70; 2) stimulate sustained duration and magnitude of extracellular signal-regulated kinase 1/2 phosphorylation, which results in stabilization of the transcription factor c-Fos, a suppressor of IL-12; and 3) yield a Th2 bias. Thus, distinct TLR agonists differentially modulate extracellular signal-regulated kinase signaling, c-Fos activity, and cytokine responses in DCs to stimulate different Th responses.
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A. Agrawal, S. Dillon, T. L. Denning, and B. Pulendran ERK1-/- Mice Exhibit Th1 Cell Polarization and Increased Susceptibility to Experimental Autoimmune Encephalomyelitis J. Immunol., May 15, 2006; 176(10): 5788 - 5796. [Abstract] [Full Text] [PDF]
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 E. Caparros, P. Munoz, E. Sierra-Filardi, D. Serrano-Gomez, A. Puig-Kroger, J. L. Rodriguez-Fernandez, M. Mellado, J. Sancho, M. Zubiaur, and A. L. Corbi DC-SIGN ligation on dendritic cells results in ERK and PI3K activation and modulates cytokine production Blood, May 15, 2006; 107(10): 3950 - 3958. [Abstract] [Full Text] [PDF]
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M. A. Delgado, J. F. Poschet, and V. Deretic Nonclassical Pathway of Pseudomonas aeruginosa DNA-Induced Interleukin-8 Secretion in Cystic Fibrosis Airway Epithelial Cells. Infect. Immun., May 1, 2006; 74(5): 2975 - 2984. [Abstract] [Full Text] [PDF]
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N. Ray, M. Kuwahara, Y. Takada, K. Maruyama, T. Kawaguchi, H. Tsubone, H. Ishikawa, and K. Matsuo c-Fos suppresses systemic inflammatory response to endotoxin Int. Immunol., May 1, 2006; 18(5): 671 - 677. [Abstract] [Full Text] [PDF]
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 E. L. Cooper Role of TOLL-like Receptors in Adjuvant-Augmented Immune Therapies by T. Seya. Evid. Based Complement. Altern. Med., March 1, 2006; 3(1): 133 - 137. [Full Text] [PDF]
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Y.-T.A. Teng Protective and Destructive Immunity in the Periodontium: Part 1--Innate and Humoral Immunity and the Periodontium Journal of Dental Research, March 1, 2006; 85(3): 198 - 208. [Abstract] [Full Text] [PDF]
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J.-S. Chang, J. F. Huggett, K. Dheda, L. U. Kim, A. Zumla, and G. A. W. Rook Myobacterium tuberculosis Induces Selective Up-Regulation of TLRs in the Mononuclear Leukocytes of Patients with Active Pulmonary Tuberculosis. J. Immunol., March 1, 2006; 176(5): 3010 - 3018. [Abstract] [Full Text] [PDF]
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A. Banerjee, R. Gugasyan, M. McMahon, and S. Gerondakis Diverse Toll-like receptors utilize Tpl2 to activate extracellular signal-regulated kinase (ERK) in hemopoietic cells PNAS, February 28, 2006; 103(9): 3274 - 3279. [Abstract] [Full Text] [PDF]
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T. Querec, S. Bennouna, S. Alkan, Y. Laouar, K. Gorden, R. Flavell, S. Akira, R. Ahmed, and B. Pulendran Yellow fever vaccine YF-17D activates multiple dendritic cell subsets via TLR2, 7, 8, and 9 to stimulate polyvalent immunity J. Exp. Med., February 21, 2006; 203(2): 413 - 424. [Abstract] [Full Text] [PDF]
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M. F. Tomczak, M. Gadjeva, Y. Y. Wang, K. Brown, I. Maroulakou, P. N. Tsichlis, S. E. Erdman, J. G. Fox, and B. H. Horwitz Defective Activation of ERK in Macrophages Lacking the p50/p105 Subunit of NF-{kappa}B Is Responsible for Elevated Expression of IL-12 p40 Observed after Challenge with Helicobacter hepaticus J. Immunol., January 15, 2006; 176(2): 1244 - 1251. [Abstract] [Full Text] [PDF]
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C.-C. Chen, S. Louie, B. A. McCormick, W. A. Walker, and H. N. Shi Helminth-Primed Dendritic Cells Alter the Host Response to Enteric Bacterial Infection J. Immunol., January 1, 2006; 176(1): 472 - 483. [Abstract] [Full Text] [PDF]
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M. Yasutomi, Y. Ohshima, N. Omata, A. Yamada, H. Iwasaki, Y. Urasaki, and M. Mayumi Erythromycin Differentially Inhibits Lipopolysaccharide- or Poly(I:C)-Induced but Not Peptidoglycan-Induced Activation of Human Monocyte-Derived Dendritic Cells J. Immunol., December 15, 2005; 175(12): 8069 - 8076. [Abstract] [Full Text] [PDF]
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H. Tada, S. Aiba, K.-I. Shibata, T. Ohteki, and H. Takada Synergistic Effect of Nod1 and Nod2 Agonists with Toll-Like Receptor Agonists on Human Dendritic Cells To Generate Interleukin-12 and T Helper Type 1 Cells Infect. Immun., December 1, 2005; 73(12): 7967 - 7976. [Abstract] [Full Text] [PDF]
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S. Appel, V. Mirakaj, A. Bringmann, M. M. Weck, F. Grunebach, and P. Brossart PPAR-{gamma} agonists inhibit toll-like receptor-mediated activation of dendritic cells via the MAP kinase and NF-{kappa}B pathways Blood, December 1, 2005; 106(12): 3888 - 3894. [Abstract] [Full Text] [PDF]
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C. A. A. van der Graaf, M. G. Netea, I. Verschueren, J. W. M. van der Meer, and B. J. Kullberg Differential Cytokine Production and Toll-Like Receptor Signaling Pathways by Candida albicans Blastoconidia and Hyphae Infect. Immun., November 1, 2005; 73(11): 7458 - 7464. [Abstract] [Full Text] [PDF]
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 M. G. Netea, J. W. M. Van der Meer, R. P. Sutmuller, G. J. Adema, and B.-J. Kullberg From the Th1/Th2 Paradigm towards a Toll-Like Receptor/T-Helper Bias Antimicrob. Agents Chemother., October 1, 2005; 49(10): 3991 - 3996. [Full Text] [PDF]
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H. Tsujimoto, T. Uchida, P. A. Efron, P. O. Scumpia, A. Verma, T. Matsumoto, S. K. Tschoeke, R. F. Ungaro, S. Ono, S. Seki, et al. Flagellin enhances NK cell proliferation and activation directly and through dendritic cell-NK cell interactions J. Leukoc. Biol., October 1, 2005; 78(4): 888 - 897. [Abstract] [Full Text] [PDF]
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S. E. Applequist, E. Rollman, M. D. Wareing, M. Liden, B. Rozell, J. Hinkula, and H.-G. Ljunggren Activation of Innate Immunity, Inflammation, and Potentiation of DNA Vaccination through Mammalian Expression of the TLR5 Agonist Flagellin J. Immunol., September 15, 2005; 175(6): 3882 - 3891. [Abstract] [Full Text] [PDF]
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L. Freeman, M. Hewison, S. V. Hughes, K. N. Evans, D. Hardie, T. K. Means, and R. Chakraverty Expression of 11{beta}-hydroxysteroid dehydrogenase type 1 permits regulation of glucocorticoid bioavailability by human dendritic cells Blood, September 15, 2005; 106(6): 2042 - 2049. [Abstract] [Full Text] [PDF]
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K. Minami, Y. Yanagawa, K. Iwabuchi, N. Shinohara, T. Harabayashi, K. Nonomura, and K. Onoe Negative feedback regulation of T helper type 1 (Th1)/Th2 cytokine balance via dendritic cell and natural killer T cell interactions Blood, September 1, 2005; 106(5): 1685 - 1693. [Abstract] [Full Text] [PDF]
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P. G. Thomas, M. R. Carter, A. A. Da'dara, T. M. DeSimone, and D. A. Harn A Helminth Glycan Induces APC Maturation via Alternative NF-{kappa}B Activation Independent of I{kappa}B{alpha} Degradation J. Immunol., August 15, 2005; 175(4): 2082 - 2090. [Abstract] [Full Text] [PDF]
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P. O. Krutzik, M. B. Hale, and G. P. Nolan Characterization of the Murine Immunological Signaling Network with Phosphospecific Flow Cytometry J. Immunol., August 15, 2005; 175(4): 2366 - 2373. [Abstract] [Full Text] [PDF]
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J. C. Salazar, C. D. Pope, M. W. Moore, J. Pope, T. G. Kiely, and J. D. Radolf Lipoprotein-Dependent and -Independent Immune Responses to Spirochetal Infection Clin. Vaccine Immunol., August 1, 2005; 12(8): 949 - 958. [Abstract] [Full Text] [PDF]
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 E Cario BACTERIAL INTERACTIONS WITH CELLS OF THE INTESTINAL MUCOSA: TOLL-LIKE RECEPTORS AND NOD2 Gut, August 1, 2005; 54(8): 1182 - 1193. [Full Text] [PDF]
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I. Zanoni, M. Foti, P. Ricciardi-Castagnoli, and F. Granucci TLR-Dependent Activation Stimuli Associated with Th1 Responses Confer NK Cell Stimulatory Capacity to Mouse Dendritic Cells J. Immunol., July 1, 2005; 175(1): 286 - 292. [Abstract] [Full Text] [PDF]
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S. Bluml, S. Kirchberger, V. N. Bochkov, G. Kronke, K. Stuhlmeier, O. Majdic, G. J. Zlabinger, W. Knapp, B. R. Binder, J. Stockl, et al. Oxidized Phospholipids Negatively Regulate Dendritic Cell Maturation Induced by TLRs and CD40 J. Immunol., July 1, 2005; 175(1): 501 - 508. [Abstract] [Full Text] [PDF]
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