| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Pulmonary Medicine, Erasmus University MC, Rotterdam, The Netherlands;
Sylviuslaboratorium, Proef Dier Centrum-Leids Universitair Medisch Centrum, Leiden, The Netherlands; and
Millennium Pharmaceuticals, Cambridge, MA 02139
The prevalence of atopic asthma, a Th2-dependent disease, is reaching epidemic proportions partly due to improved hygiene in industrialized countries. There is an inverse correlation between the level of environmental endotoxin exposure and the prevalence of atopic sensitization. As dendritic cells (DC) have been implicated in causing sensitization to inhaled Ag, we studied the effect of endotoxin on Th2 development induced by bone marrow DC in vitro and by intratracheal injection in vivo, with particular emphasis on the role played by the polarizing cytokine IL-12. Bone marrow-derived DC stimulated with Escherichia coli O26:B6 LPS produced IL-12p70 for a limited period of time, after which production became refractory to further stimulation with CD40 ligand, a phenomenon previously called "exhaustion." The level of IL-12 production of DC did not correlate with Th1 development, as exhausted OVA-pulsed DC were still capable of shifting the cytokine pattern of responding OVA-specific Th cells toward Th1 in vitro and in vivo. When mice were first immunized by intratracheal injection of OVA-DC and subsequently challenged with OVA aerosol, prior in vitro stimulation of DC with LPS reduced the development of airway eosinophilia and Th2 cytokine production. Most surprisingly, the capacity of LPS to reduce Th2-dependent eosinophilic airway inflammation was IL-12-independent altogether, as IL-12p40 knockout DC had a similar reduced capacity to prime for Th2 responses. These results suggest that LPS reduces sensitization to inhaled Ag by reducing DC-driven Th2 development, but that IL-12 is not necessary for this effect.
Related articles in The JI:
This article has been cited by other articles:
|
|
 |
|
  W. Duan, T. So, and M. Croft Antagonism of Airway Tolerance by Endotoxin/Lipopolysaccharide through Promoting OX40L and Suppressing Antigen-Specific Foxp3+ T Regulatory Cells J. Immunol., December 15, 2008; 181(12): 8650 - 8659. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Gorelik, M. Kauth, K. Gehlhar, A. Bufe, O. Holst, and M. Peters Modulation of dendritic cell function by cowshed dust extract Innate Immunity, December 1, 2008; 14(6): 345 - 355. [Abstract] [PDF]
|
|
|
|
 |
|
 F. W. van Ginkel, T. Iwamoto, B. D. Schultz, and J. M. Tomich Immunity to a Self-Derived, Channel-Forming Peptide in the Respiratory Tract Clin. Vaccine Immunol., February 1, 2008; 15(2): 260 - 266. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. K. Oyoshi, P. Bryce, S. Goya, M. Pichavant, D. T. Umetsu, H. C. Oettgen, and E. N. Tsitsikov TNF Receptor-Associated Factor 1 Expressed in Resident Lung Cells Is Required for the Development of Allergic Lung Inflammation J. Immunol., February 1, 2008; 180(3): 1878 - 1885. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sel, M. Wegmann, S. Sel, S. Bauer, H. Garn, G. Alber, and H. Renz Immunomodulatory Effects of Viral TLR Ligands on Experimental Asthma Depend on the Additive Effects of IL-12 and IL-10 J. Immunol., June 15, 2007; 178(12): 7805 - 7813. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-K. Kim, S.-Y. Oh, S. G. Jeon, H.-W. Park, S.-Y. Lee, E.-Y. Chun, B. Bang, H.-S. Lee, M.-H. Oh, Y.-S. Kim, et al. Airway Exposure Levels of Lipopolysaccharide Determine Type 1 versus Type 2 Experimental Asthma J. Immunol., April 15, 2007; 178(8): 5375 - 5382. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Faith, E. Peek, J. McDonald, Z. Urry, D. F. Richards, C. Tan, G. Santis, and C. Hawrylowicz Plasmacytoid Dendritic Cells from Human Lung Cancer Draining Lymph Nodes Induce Tc1 Responses Am. J. Respir. Cell Mol. Biol., March 1, 2007; 36(3): 360 - 367. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. W. Hellings, A. Kasran, D. Bullens, L. Overbergh, C. Mathieu, H. Heremans, P. Matthys, L. Boon, M. Jorissen, and J. L. Ceuppens IL-10- and IL-12-Independent Down-Regulation of Allergic Sensitization by Stimulation of CD40 Signaling J. Immunol., October 15, 2006; 177(8): 5138 - 5144. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Wikstrom, E. Batanero, M. Smith, J. A. Thomas, C. von Garnier, P. G. Holt, and P. A. Stumbles Influence of Mucosal Adjuvants on Antigen Passage and CD4+ T Cell Activation during the Primary Response to Airborne Allergen J. Immunol., July 15, 2006; 177(2): 913 - 924. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Vermaelen and R. Pauwels Pulmonary Dendritic Cells Am. J. Respir. Crit. Care Med., September 1, 2005; 172(5): 530 - 551. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Miyazaki, H. Inoue, M. Matsumura, K. Matsumoto, T. Nakano, M. Tsuda, S. Hamano, A. Yoshimura, and H. Yoshida Exacerbation of Experimental Allergic Asthma by Augmented Th2 Responses in WSX-1-Deficient Mice J. Immunol., August 15, 2005; 175(4): 2401 - 2407. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Bozanich, R. A. Collins, C. Thamrin, Z. Hantos, P. D. Sly, and D. J. Turner Developmental changes in airway and tissue mechanics in mice J Appl Physiol, July 1, 2005; 99(1): 108 - 113. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Revets, G. Pynaert, J. Grooten, and P. De Baetselier Lipoprotein I, a TLR2/4 Ligand Modulates Th2-Driven Allergic Immune Responses J. Immunol., January 15, 2005; 174(2): 1097 - 1103. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kuipers, C. Heirman, D. Hijdra, F. Muskens, M. Willart, S. van Meirvenne, K. Thielemans, H. C. Hoogsteden, and B. N. Lambrecht Dendritic cells retrovirally overexpressing IL-12 induce strong Th1 responses to inhaled antigen in the lung but fail to revert established Th2 sensitization J. Leukoc. Biol., November 1, 2004; 76(5): 1028 - 1038. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Bhatt, S. P. Hickman, and P. Salgame Cutting Edge: A New Approach to Modeling Early Lung Immunity in Murine Tuberculosis J. Immunol., March 1, 2004; 172(5): 2748 - 2751. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
