| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CUTTING EDGE |
Departments of
*
Medicine and
Pharmacology, University of California, San Diego, La Jolla, CA 92093; and
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231
Recognition of microbial components by APCs and their activation through Toll-like receptors (TLR) leads to the induction of adaptive immune responses. In this study, we show that activation of TLR2 by its synthetic ligand Pam3Cys, in contrast to activation of TLR9 by immunostimulatory DNA (ISS-ODN), induces a prominent Th2-biased immune response. Activation of APCs by Pam3Cys resulted in the induction of Th2-associated effector molecules like IL-13, and IL-1
, GM-CSF and up-regulation of B7RP-1, but low levels of Th1-associated cytokines (IL-12, IFN
, IL-18, IL-27). Accordingly, TLR2 ligands aggravated experimental asthma. These data indicate that the type of TLR stimulation during the initial phase of immune activation determines the polarization of the adaptive immune response and may play a role in the initiation of Th2-mediated immune disorders, such as asthma.
Related articles in The JI:
This article has been cited by other articles:
|
|
 |
|
  K. Page, J. R. Ledford, P. Zhou, and M. Wills-Karp A TLR2 Agonist in German Cockroach Frass Activates MMP-9 Release and Is Protective against Allergic Inflammation in Mice J. Immunol., September 1, 2009; 183(5): 3400 - 3408. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Yu, R. Vazquez, E. V. Khojeini, C. Patel, R. Venkataramani, and D. F. Larson IL-18 induction of osteopontin mediates cardiac fibrosis and diastolic dysfunction in mice Am J Physiol Heart Circ Physiol, July 1, 2009; 297(1): H76 - H85. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Phipps, C. E. Lam, G. E. Kaiko, S. Y. Foo, A. Collison, J. Mattes, J. Barry, S. Davidson, K. Oreo, L. Smith, et al. Toll/IL-1 Signaling Is Critical for House Dust Mite-specific Th1 and Th2 Responses Am. J. Respir. Crit. Care Med., May 15, 2009; 179(10): 883 - 893. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. W. Finn and T. D. Bigby Innate Immunity and Asthma Proceedings of the ATS, May 1, 2009; 6(3): 260 - 265. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Gaucher, R. Therrien, N. Kettaf, B. R. Angermann, G. Boucher, A. Filali-Mouhim, J. M. Moser, R. S. Mehta, D. R. Drake III, E. Castro, et al. Yellow fever vaccine induces integrated multilineage and polyfunctional immune responses J. Exp. Med., December 22, 2008; 205(13): 3119 - 3131. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Magalhaes, J. H. Fritz, L. Le Bourhis, G. Sellge, L. H. Travassos, T. Selvanantham, S. E. Girardin, J. L. Gommerman, and D. J. Philpott Nod2-Dependent Th2 Polarization of Antigen-Specific Immunity J. Immunol., December 1, 2008; 181(11): 7925 - 7935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Dittrich, H.-C. Chen, L. Xu, P. Ranney, S. Connolly, T. O. Yarovinsky, and H. K. Bottomly A New Mechanism for Inhalational Priming: IL-4 Bypasses Innate Immune Signals J. Immunol., November 15, 2008; 181(10): 7307 - 7315. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kiyokawa, S. Akashi-Takamura, T. Shibata, F. Matsumoto, C. Nishitani, Y. Kuroki, Y. Seto, and K. Miyake A single base mutation in the PRAT4A gene reveals differential interaction of PRAT4A with Toll-like receptors Int. Immunol., November 1, 2008; 20(11): 1407 - 1415. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Hudson, G. P. Christophi, R. C. Gruber, J. R. Wilmore, D. A. Lawrence, and P. T. Massa Induction of IL-33 expression and activity in central nervous system glia J. Leukoc. Biol., September 1, 2008; 84(3): 631 - 643. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Page, K. M. Lierl, V. S. Hughes, P. Zhou, J. R. Ledford, and M. Wills-Karp TLR2-Mediated Activation of Neutrophils in Response to German Cockroach Frass J. Immunol., May 1, 2008; 180(9): 6317 - 6324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B J Hales, L J Pearce, M M H Kusel, P G Holt, P D Sly, and W R Thomas Differences in the antibody response to a mucosal bacterial antigen between allergic and non-allergic subjectsSmoke-free legislation reduces exposure in children Thorax, March 1, 2008; 63(3): 221 - 227. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. E. Kaiko, S. Phipps, D. K. Hickey, C. E. Lam, P. M. Hansbro, P. S. Foster, and K. W. Beagley Chlamydia muridarum Infection Subverts Dendritic Cell Function to Promote Th2 Immunity and Airways Hyperreactivity J. Immunol., February 15, 2008; 180(4): 2225 - 2232. [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]
|
|
|
|
 |
|
 F. Fransen, C. J. Boog, J. P. van Putten, and P. van der Ley Agonists of Toll-Like Receptors 3, 4, 7, and 9 Are Candidates for Use as Adjuvants in an Outer Membrane Vaccine against Neisseria meningitidis Serogroup B Infect. Immun., December 1, 2007; 75(12): 5939 - 5946. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Pirhonen, J. Siren, I. Julkunen, and S. Matikainen IFN-{alpha} regulates Toll-like receptor-mediated IL-27 gene expression in human macrophages J. Leukoc. Biol., November 1, 2007; 82(5): 1185 - 1192. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. W. J. Schroder and M. Arditi IEIIS Meeting minireview: The role of innate immunity in the pathogenesis of asthma: evidence for the involvement of Toll-like receptor signaling Innate Immunity, October 1, 2007; 13(5): 305 - 312. [Abstract] [PDF]
|
|
|
|
|
|
H. Izadi, A. T. Motameni, T. C. Bates, E. R. Olivera, V. Villar-Suarez, I. Joshi, R. Garg, B. A. Osborne, R. J. Davis, M. Rincon, et al. c-Jun N-Terminal Kinase 1 Is Required for Toll-Like Receptor 1 Gene Expression in Macrophages Infect. Immun., October 1, 2007; 75(10): 5027 - 5034. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Bevelander, J. Mayette, L. A. Whittaker, S. A. Paveglio, C. C. Jones, J. Robbins, D. Hemenway, S. Akira, S. Uematsu, and M. E. Poynter Nitrogen Dioxide Promotes Allergic Sensitization to Inhaled Antigen J. Immunol., September 15, 2007; 179(6): 3680 - 3688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. S. Bandukwala, B. S. Clay, J. Tong, P. D. Mody, J. L. Cannon, R. A. Shilling, J. S. Verbeek, J. V. Weinstock, J. Solway, and A. I. Sperling Signaling through Fc{gamma}RIII is required for optimal T helper type (Th)2 responses and Th2-mediated airway inflammation J. Exp. Med., August 6, 2007; 204(8): 1875 - 1889. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. K. Wong, P. F. Y. Cheung, W. K. Ip, and C. W. K. Lam Intracellular Signaling Mechanisms Regulating Toll-Like Receptor-Mediated Activation of Eosinophils Am. J. Respir. Cell Mol. Biol., July 1, 2007; 37(1): 85 - 96. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Fichtner-Feigl, I. J. Fuss, C. A. Young, T. Watanabe, E. K. Geissler, H.-J. Schlitt, A. Kitani, and W. Strober Induction of IL-13 Triggers TGF-beta1-Dependent Tissue Fibrosis in Chronic 2,4,6-Trinitrobenzene Sulfonic Acid Colitis J. Immunol., May 1, 2007; 178(9): 5859 - 5870. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hamm, A. Heit, M. Koffler, K. M. Huster, S. Akira, D. H. Busch, H. Wagner, and S. Bauer Immunostimulatory RNA is a potent inducer of antigen-specific cytotoxic and humoral immune response in vivo Int. Immunol., March 1, 2007; 19(3): 297 - 304. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. O. Aliprantis, J. Wang, J. W. Fathman, R. Lemaire, D. M. Dorfman, R. Lafyatis, and L. H. Glimcher Transcription factor T-bet regulates skin sclerosis through its function in innate immunity and via IL-13 PNAS, February 20, 2007; 104(8): 2827 - 2830. [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]
|
|
|
|
|
|
R. Lang, M. Hammer, and J. Mages DUSP Meet Immunology: Dual Specificity MAPK Phosphatases in Control of the Inflammatory Response J. Immunol., December 1, 2006; 177(11): 7497 - 7504. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Fujimoto, C.-R. Yu, G. Shi, B. P. Vistica, E. F. Wawrousek, D. M. Klinman, C.-C. Chan, C. E. Egwuagu, and I. Gery Pertussis Toxin Is Superior to TLR Ligands in Enhancing Pathogenic Autoimmunity, Targeted at a Neo-Self Antigen, by Triggering Robust Expansion of Th1 Cells and Their Cytokine Production J. Immunol., November 15, 2006; 177(10): 6896 - 6903. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Hasebe, N. D. Pennock, H.-H. Mu, F. V. Chan, M. L. Taylor, and B. C. Cole A Microbial TLR2 Agonist Imparts Macrophage-Activating Ability to Apolipoprotein A-1 J. Immunol., October 1, 2006; 177(7): 4826 - 4832. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. J. Brown, S. H. Sacks, and M. G. Robson Toll-Like Receptor 2 Agonists Exacerbate Accelerated Nephrotoxic Nephritis J. Am. Soc. Nephrol., July 1, 2006; 17(7): 1931 - 1939. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. W. Denning, B. R. O'Driscoll, C. M. Hogaboam, P. Bowyer, and R. M. Niven The link between fungi and severe asthma: a summary of the evidence. Eur. Respir. J., March 1, 2006; 27(3): 615 - 626. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 H. Qiao, M. V. Andrade, F. A. Lisboa, K. Morgan, and M. A. Beaven Fc{epsilon}R1 and toll-like receptors mediate synergistic signals to markedly augment production of inflammatory cytokines in murine mast cells Blood, January 15, 2006; 107(2): 610 - 618. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
S. N. Georas, J. Guo, U. De Fanis, and V. Casolaro T-helper cell type-2 regulation in allergic disease Eur. Respir. J., December 1, 2005; 26(6): 1119 - 1137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 F Y Liew, M Patel, and D Xu Toll-like receptor 2 signalling and inflammation Ann Rheum Dis, November 1, 2005; 64(suppl_4): iv104 - iv105. [Full Text] [PDF]
|
|
|
|
|
|
C. S. Jack, N. Arbour, J. Manusow, V. Montgrain, M. Blain, E. McCrea, A. Shapiro, and J. P. Antel TLR Signaling Tailors Innate Immune Responses in Human Microglia and Astrocytes J. Immunol., October 1, 2005; 175(7): 4320 - 4330. [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]
|
|
|
|
|
|
M. Patel, D. Xu, P. Kewin, B. Choo-Kang, C. McSharry, N. C. Thomson, and F. Y. Liew TLR2 Agonist Ameliorates Established Allergic Airway Inflammation by Promoting Th1 Response and Not via Regulatory T Cells J. Immunol., June 15, 2005; 174(12): 7558 - 7563. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. F. Benjamim, S. K. Lundy, N. W. Lukacs, C. M. Hogaboam, and S. L. Kunkel Reversal of long-term sepsis-induced immunosuppression by dendritic cells Blood, May 1, 2005; 105(9): 3588 - 3595. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Zanin-Zhorov, R. Bruck, G. Tal, S. Oren, H. Aeed, R. Hershkoviz, I. R. Cohen, and O. Lider Heat Shock Protein 60 Inhibits Th1-Mediated Hepatitis Model via Innate Regulation of Th1/Th2 Transcription Factors and Cytokines J. Immunol., March 15, 2005; 174(6): 3227 - 3236. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Velasco, M. Campo, O. J. Manrique, A. Bellou, H. He, R. S. S. Arestides, B. Schaub, D. L. Perkins, and P. W. Finn Toll-Like Receptor 4 or 2 Agonists Decrease Allergic Inflammation Am. J. Respir. Cell Mol. Biol., March 1, 2005; 32(3): 218 - 224. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Vakharia and J. P. Hinson Lipopolysaccharide Directly Stimulates Cortisol Secretion by Human Adrenal Cells by a Cyclooxygenase-Dependent Mechanism Endocrinology, March 1, 2005; 146(3): 1398 - 1402. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Pulendran Variegation of the Immune Response with Dendritic Cells and Pathogen Recognition Receptors J. Immunol., March 1, 2005; 174(5): 2457 - 2465. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Sun, M. Walsh, A. V. Villarino, L. Cervi, C. A. Hunter, Y. Choi, and E. J. Pearce TLR Ligands Can Activate Dendritic Cells to Provide a MyD88-Dependent Negative Signal for Th2 Cell Development J. Immunol., January 15, 2005; 174(2): 742 - 751. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Q. Khan, Q. Chen, Z.-Q. Wu, J. C. Paton, and C. M. Snapper Both Innate Immunity and Type 1 Humoral Immunity to Streptococcus pneumoniae Are Mediated by MyD88 but Differ in Their Relative Levels of Dependence on Toll-Like Receptor 2 Infect. Immun., January 1, 2005; 73(1): 298 - 307. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Re and J. L. Strominger IL-10 Released by Concomitant TLR2 Stimulation Blocks the Induction of a Subset of Th1 Cytokines That Are Specifically Induced by TLR4 or TLR3 in Human Dendritic Cells J. Immunol., December 15, 2004; 173(12): 7548 - 7555. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Matsushima, N. Yamada, H. Matsue, and S. Shimada TLR3-, TLR7-, and TLR9-Mediated Production of Proinflammatory Cytokines and Chemokines from Murine Connective Tissue Type Skin-Derived Mast Cells but Not from Bone Marrow-Derived Mast Cells J. Immunol., July 1, 2004; 173(1): 531 - 541. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
