| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of
*
Pathobiology and
Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104
During infection, CD4+ Th cell responses polarize to become primarily Th1 or Th2. Th1 cells, which make IFN-
, are crucial for immunity to many bacterial and protozoal infections, whereas Th2 cells, which make IL-4, IL-5, and IL-13, are important for resistance to helminth infections. Polarized Th1 responses are induced by dendritic cells (DCs), which respond to pathogen-derived TLR ligands to produce IL-12 and related cytokines that are instrumental in Th1 cell outgrowth, and coordinately process and present Ag in the context of MHC class II to activate naive Th cells. In this study we show that in addition to providing positive signals for Th1 cell development, mouse DCs activated by TLR engagement can also provide a potent negative signal that prevents the development of Th2 cells. Production of this signal, which is not IL-12, IL-18, IL-23, IL-27, or IFN- and is not provided via Th1 cells, is dependent upon a MyD88-dependent, TNF receptor-associated factor-6-independent signaling pathway in DCs. The signal is released from DCs in response to activation via TLR ligands and exerts an effect directly on Th cells rather than through a third-party cell. Our findings indicate that DCs can provide potent negative as well as positive instruction for Th response polarization, and that these instructional signals are distinct and independent.
This article has been cited by other articles:
|
|
 |
|
  J. Dai, N. J. Megjugorac, G. E. Gallagher, R. Y. L. Yu, and G. Gallagher IFN-{lambda}1 (IL-29) inhibits GATA3 expression and suppresses Th2 responses in human naive and memory T cells Blood, June 4, 2009; 113(23): 5829 - 5838. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Henry, D. A. Ornelles, L. M. Mitchell, K. L. Brzoza-Lewis, and E. M. Hiltbold IL-12 Produced by Dendritic Cells Augments CD8+ T Cell Activation through the Production of the Chemokines CCL1 and CCL17 J. Immunol., December 15, 2008; 181(12): 8576 - 8584. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Fairweather, S. Frisancho-Kiss, and N. R. Rose Sex Differences in Autoimmune Disease from a Pathological Perspective Am. J. Pathol., September 1, 2008; 173(3): 600 - 609. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Krawczyk, J. Sun, and E. J. Pearce Th2 Differentiation Is Unaffected by Jagged2 Expression on Dendritic Cells J. Immunol., June 15, 2008; 180(12): 7931 - 7937. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Woods, P. Soulas-Sprauel, B. Jaulhac, B. Arditi, A.-M. Knapp, J.-L. Pasquali, A.-S. Korganow, and T. Martin MyD88 Negatively Controls Hypergammaglobulinemia with Autoantibody Production during Bacterial Infection Infect. Immun., April 1, 2008; 76(4): 1657 - 1667. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Sun, C. J. Krawczyk, and E. J. Pearce Suppression of Th2 Cell Development by Notch Ligands Delta1 and Delta4 J. Immunol., February 1, 2008; 180(3): 1655 - 1661. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Yang, Q. Chen, S. B. Su, P. Zhang, K. Kurosaka, R. R. Caspi, S. M. Michalek, H. F. Rosenberg, N. Zhang, and J. J. Oppenheim Eosinophil-derived neurotoxin acts as an alarmin to activate the TLR2-MyD88 signal pathway in dendritic cells and enhances Th2 immune responses J. Exp. Med., January 21, 2008; 205(1): 79 - 90. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Raymond, M. Schaller, C. M. Hogaboam, N. W. Lukacs, R. Rochford, and S. L. Kunkel Toll-like Receptors, Notch Ligands, and Cytokines Drive the Chronicity of Lung Inflammation Proceedings of the ATS, December 1, 2007; 4(8): 635 - 641. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Schaller, R. Neupane, B. D. Rudd, S. L. Kunkel, L. E. Kallal, P. Lincoln, J. B. Lowe, Y. Man, and N. W. Lukacs Notch ligand Delta-like 4 regulates disease pathogenesis during respiratory viral infections by modulating Th2 cytokines J. Exp. Med., November 26, 2007; 204(12): 2925 - 2934. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Johnson and P. Scott STAT1 Expression in Dendritic Cells, but Not T Cells, Is Required for Immunity to Leishmania major J. Immunol., June 1, 2007; 178(11): 7259 - 7266. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Rigano, B. Buttari, E. Profumo, E. Ortona, F. Delunardo, P. Margutti, V. Mattei, A. Teggi, M. Sorice, and A. Siracusano Echinococcus granulosus Antigen B Impairs Human Dendritic Cell Differentiation and Polarizes Immature Dendritic Cell Maturation towards a Th2 Cell Response Infect. Immun., April 1, 2007; 75(4): 1667 - 1678. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Sun and E. J. Pearce Suppression of Early IL-4 Production Underlies the Failure of CD4 T Cells Activated by TLR-Stimulated Dendritic Cells to Differentiate into Th2 Cells J. Immunol., February 1, 2007; 178(3): 1635 - 1644. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Wang, R. M. McLoughlin, B. A. Cobb, M. Charrel-Dennis, K. J. Zaleski, D. Golenbock, A. O. Tzianabos, and D. L. Kasper A bacterial carbohydrate links innate and adaptive responses through Toll-like receptor 2 J. Exp. Med., December 25, 2006; 203(13): 2853 - 2863. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Rivera, H. L. Van Epps, T. M. Hohl, G. Rizzuto, and E. G. Pamer Distinct CD4+-T-Cell Responses to Live and Heat-Inactivated Aspergillus fumigatus Conidia Infect. Immun., November 1, 2005; 73(11): 7170 - 7179. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-Y. Huang, K. J. Ishii, S. Akira, J. Aliberti, and B. Golding Th1-Like Cytokine Induction by Heat-Killed Brucella abortus Is Dependent on Triggering of TLR9 J. Immunol., September 15, 2005; 175(6): 3964 - 3970. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
