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CUTTING EDGE |
*
Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84132;
Institute for Medical Microbiology and Immunology, Technical University of Munich, Muenchen, Germany; and
Tularik, Inc., South San Francisco, CA 94080
The agent of Lyme disease, Borrelia burgdorferi,
produces membrane lipoproteins possessing potent inflammatory
properties linked to disease pathology. The recent association of
toll-like receptors (TLR) 2 and 4 with LPS responses prompted the
examination of TLR involvement in lipoprotein signaling. The ability of
human cell lines to respond to lipoproteins was correlated with the
expression of TLR2. Transfection of TLR2 into cell lines conferred
responsiveness to lipoproteins, lipopeptides, and sonicated B.
burgdorferi, as measured by nuclear translocation of NF-
B
and cytokine production. The physiological importance of this
interaction was demonstrated by the 10-fold greater sensitivity of
TLR2-transfected cells to lipoproteins than LPS. Futhermore,
TLR2-dependant signaling by lipoproteins was facilitated by CD14. These
data indicate that TLR2 facilitates the inflammatory events associated
with Lyme arthritis. In addition, the widespread expression of
lipoproteins by other bacterial species suggests that this interaction
may have broad implications in microbial inflammation and
pathogenesis.
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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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C. S. Berenson, T. F. Murphy, C. T. Wrona, and S. Sethi Outer Membrane Protein P6 of Nontypeable Haemophilus influenzae Is a Potent and Selective Inducer of Human Macrophage Proinflammatory Cytokines Infect. Immun., May 1, 2005; 73(5): 2728 - 2735. [Abstract] [Full Text] [PDF]
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K. Craig-Mylius, G. F. Weber, J. Coburn, and L. Glickstein Borrelia burgdorferi, an extracellular pathogen, circumvents osteopontin in inducing an inflammatory cytokine response J. Leukoc. Biol., May 1, 2005; 77(5): 710 - 718. [Abstract] [Full Text] [PDF]
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S. Ghosh, A. C. Steere, B. D. Stollar, and B. T. Huber In Situ Diversification of the Antibody Repertoire in Chronic Lyme Arthritis Synovium J. Immunol., March 1, 2005; 174(5): 2860 - 2869. [Abstract] [Full Text] [PDF]
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M. Akamine, F. Higa, N. Arakaki, K. Kawakami, K. Takeda, S. Akira, and A. Saito Differential Roles of Toll-Like Receptors 2 and 4 in In Vitro Responses of Macrophages to Legionella pneumophila Infect. Immun., January 1, 2005; 73(1): 352 - 361. [Abstract] [Full Text] [PDF]
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X. Wang, Y. Ma, J. H. Weis, J. F. Zachary, C. J. Kirschning, and J. J. Weis Relative Contributions of Innate and Acquired Host Responses to Bacterial Control and Arthritis Development in Lyme Disease Infect. Immun., January 1, 2005; 73(1): 657 - 660. [Abstract] [Full Text] [PDF]
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T. Vasselon, P. A. Detmers, D. Charron, and A. Haziot TLR2 Recognizes a Bacterial Lipopeptide through Direct Binding J. Immunol., December 15, 2004; 173(12): 7401 - 7405. [Abstract] [Full Text] [PDF]
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N. Hyakushima, H. Mitsuzawa, C. Nishitani, H. Sano, K. Kuronuma, M. Konishi, T. Himi, K. Miyake, and Y. Kuroki Interaction of Soluble Form of Recombinant Extracellular TLR4 Domain with MD-2 Enables Lipopolysaccharide Binding and Attenuates TLR4-Mediated Signaling J. Immunol., December 1, 2004; 173(11): 6949 - 6954. [Abstract] [Full Text] [PDF]
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G. H. Giambartolomei, A. Zwerdling, J. Cassataro, L. Bruno, C. A. Fossati, and M. T. Philipp Lipoproteins, Not Lipopolysaccharide, Are the Key Mediators of the Proinflammatory Response Elicited by Heat-Killed Brucella abortus J. Immunol., October 1, 2004; 173(7): 4635 - 4642. [Abstract] [Full Text] [PDF]
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A. J. Gehring, K. M. Dobos, J. T. Belisle, C. V. Harding, and W. H. Boom Mycobacterium tuberculosis LprG (Rv1411c): A Novel TLR-2 Ligand That Inhibits Human Macrophage Class II MHC Antigen Processing J. Immunol., August 15, 2004; 173(4): 2660 - 2668. [Abstract] [Full Text] [PDF]
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N. W. J. Schroder, H. Heine, C. Alexander, M. Manukyan, J. Eckert, L. Hamann, U. B. Gobel, and R. R. Schumann Lipopolysaccharide Binding Protein Binds to Triacylated and Diacylated Lipopeptides and Mediates Innate Immune Responses J. Immunol., August 15, 2004; 173(4): 2683 - 2691. [Abstract] [Full Text] [PDF]
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M. Siedlar, M. Frankenberger, E. Benkhart, T. Espevik, M. Quirling, K. Brand, M. Zembala, and L. Ziegler-Heitbrock Tolerance Induced by the Lipopeptide Pam3Cys Is Due to Ablation of IL-1R-Associated Kinase-1 J. Immunol., August 15, 2004; 173(4): 2736 - 2745. [Abstract] [Full Text] [PDF]
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D. D. Bolz, R. S. Sundsbak, Y. Ma, S. Akira, C. J. Kirschning, J. F. Zachary, J. H. Weis, and J. J. Weis MyD88 Plays a Unique Role in Host Defense but Not Arthritis Development in Lyme Disease J. Immunol., August 1, 2004; 173(3): 2003 - 2010. [Abstract] [Full Text] [PDF]
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N. Liu, R. R. Montgomery, S. W. Barthold, and L. K. Bockenstedt Myeloid Differentiation Antigen 88 Deficiency Impairs Pathogen Clearance but Does Not Alter Inflammation in Borrelia burgdorferi-Infected Mice Infect. Immun., June 1, 2004; 72(6): 3195 - 3203. [Abstract] [Full Text] [PDF]
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A.-H. Hovav, L. Davidovitch, G. Nussbaum, J. Mullerad, Y. Fishman, and H. Bercovier Mitogenicity of the Recombinant Mycobacterial 27-Kilodalton Lipoprotein Is Not Connected to Its Antiprotective Effect Infect. Immun., June 1, 2004; 72(6): 3383 - 3390. [Abstract] [Full Text] [PDF]
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J. J. Shin, A. V. Bryksin, H. P. Godfrey, and F. C. Cabello Localization of BmpA on the Exposed Outer Membrane of Borrelia burgdorferi by Monospecific Anti-Recombinant BmpA Rabbit Antibodies Infect. Immun., April 1, 2004; 72(4): 2280 - 2287. [Abstract] [Full Text] [PDF]
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T. Okusawa, M. Fujita, J.-i. Nakamura, T. Into, M. Yasuda, A. Yoshimura, Y. Hara, A. Hasebe, D. T. Golenbock, M. Morita, et al. Relationship between Structures and Biological Activities of Mycoplasmal Diacylated Lipopeptides and Their Recognition by Toll-Like Receptors 2 and 6 Infect. Immun., March 1, 2004; 72(3): 1657 - 1665. [Abstract] [Full Text] [PDF]
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S. Knapp, C. W. Wieland, C. van 't Veer, O. Takeuchi, S. Akira, S. Florquin, and T. van der Poll Toll-Like Receptor 2 Plays a Role in the Early Inflammatory Response to Murine Pneumococcal Pneumonia but Does Not Contribute to Antibacterial Defense J. Immunol., March 1, 2004; 172(5): 3132 - 3138. [Abstract] [Full Text] [PDF]
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M. A. Campos, G. M. S. Rosinha, I. C. Almeida, X. S. Salgueiro, B. W. Jarvis, G. A. Splitter, N. Qureshi, O. Bruna-Romero, R. T. Gazzinelli, and S. C. Oliveira Role of Toll-Like Receptor 4 in Induction of Cell-Mediated Immunity and Resistance to Brucella abortus Infection in Mice Infect. Immun., January 1, 2004; 72(1): 176 - 186. [Abstract] [Full Text] [PDF]
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P. L. Fisette, S. Ram, J. M. Andersen, W. Guo, and R. R. Ingalls The Lip Lipoprotein from Neisseria gonorrhoeae Stimulates Cytokine Release and NF-{kappa}B Activation in Epithelial Cells in a Toll-like Receptor 2-dependent Manner J. Biol. Chem., November 21, 2003; 278(47): 46252 - 46260. [Abstract] [Full Text] [PDF]
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K. Saito, T. Yajima, H. Nishimura, K. Aiba, R. Ishimitsu, T. Matsuguchi, T. Fushimi, Y. Ohshima, Y. Tsukamoto, and Y. Yoshikai Soluble Branched {beta}-(1,4)Glucans from Acetobacter Species Show Strong Activities to Induce Interleukin-12 in Vitro and Inhibit T-helper 2 Cellular Response with Immunoglobulin E Production in Vivo J. Biol. Chem., October 3, 2003; 278(40): 38571 - 38578. [Abstract] [Full Text] [PDF]
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J. L. Coleman and J. L. Benach The Urokinase Receptor Can Be Induced by Borrelia burgdorferi through Receptors of the Innate Immune System Infect. Immun., October 1, 2003; 71(10): 5556 - 5564. [Abstract] [Full Text] [PDF]
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M. Fujita, T. Into, M. Yasuda, T. Okusawa, S. Hamahira, Y. Kuroki, A. Eto, T. Nisizawa, M. Morita, and K.-i. Shibata Involvement of Leucine Residues at Positions 107, 112, and 115 in a Leucine-Rich Repeat Motif of Human Toll-Like Receptor 2 in the Recognition of Diacylated Lipoproteins and Lipopeptides and Staphylococcus aureus Peptidoglycans J. Immunol., October 1, 2003; 171(7): 3675 - 3683. [Abstract] [Full Text] [PDF]
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 F. Hayashi, T. K. Means, and A. D. Luster Toll-like receptors stimulate human neutrophil function Blood, October 1, 2003; 102(7): 2660 - 2669. [Abstract] [Full Text] [PDF]
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K. Sau, S. S. Mambula, E. Latz, P. Henneke, D. T. Golenbock, and S. M. Levitz The Antifungal Drug Amphotericin B Promotes Inflammatory Cytokine Release by a Toll-like Receptor- and CD14-dependent Mechanism J. Biol. Chem., September 26, 2003; 278(39): 37561 - 37568. [Abstract] [Full Text] [PDF]
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N. W. J. Schroder, U. Schombel, H. Heine, U. B. Gobel, U. Zahringer, and R. R. Schumann Acylated Cholesteryl Galactoside as a Novel Immunogenic Motif in Borrelia burgdorferi Sensu Stricto J. Biol. Chem., September 5, 2003; 278(36): 33645 - 33653. [Abstract] [Full Text] [PDF]
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J. C. Leemans, M. Heikens, K. P. M. van Kessel, S. Florquin, and T. van der Poll Lipoteichoic Acid and Peptidoglycan from Staphylococcus aureus Synergistically Induce Neutrophil Influx into the Lungs of Mice Clin. Vaccine Immunol., September 1, 2003; 10(5): 950 - 953. [Abstract] [Full Text] [PDF]
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C. A. Forestal, J. L. Benach, C. Carbonara, J. K. Italo, T. J. Lisinski, and M. B. Furie Francisella tularensis Selectively Induces Proinflammatory Changes in Endothelial Cells J. Immunol., September 1, 2003; 171(5): 2563 - 2570. [Abstract] [Full Text] [PDF]
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J. C. Salazar, C. D. Pope, T. J. Sellati, H. M. Feder Jr, T. G. Kiely, K. R. Dardick, R. L. Buckman, M. W. Moore, M. J. Caimano, J. G. Pope, et al. Coevolution of Markers of Innate and Adaptive Immunity in Skin and Peripheral Blood of Patients with Erythema Migrans J. Immunol., September 1, 2003; 171(5): 2660 - 2670. [Abstract] [Full Text] [PDF]
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M. F. Smith Jr., A. Mitchell, G. Li, S. Ding, A. M. Fitzmaurice, K. Ryan, S. Crowe, and J. B. Goldberg Toll-like Receptor (TLR) 2 and TLR5, but Not TLR4, Are Required for Helicobacter pylori-induced NF-{kappa}B Activation and Chemokine Expression by Epithelial Cells J. Biol. Chem., August 29, 2003; 278(35): 32552 - 32560. [Abstract] [Full Text] [PDF]
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R. I. Tapping and P. S. Tobias Mycobacterial lipoarabinomannan mediates physical interactions between TLR1 and TLR2 to induce signaling Innate Immunity, August 1, 2003; 9(4): 264 - 268. [Abstract] [PDF]
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H. M. Paterson, T. J. Murphy, E. J. Purcell, O. Shelley, S. J. Kriynovich, E. Lien, J. A. Mannick, and J. A. Lederer Injury Primes the Innate Immune System for Enhanced Toll-Like Receptor Reactivity J. Immunol., August 1, 2003; 171(3): 1473 - 1483. [Abstract] [Full Text] [PDF]
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 E. S. Van Amersfoort, T. J. C. Van Berkel, and J. Kuiper Receptors, Mediators, and Mechanisms Involved in Bacterial Sepsis and Septic Shock Clin. Microbiol. Rev., July 1, 2003; 16(3): 379 - 414. [Abstract] [Full Text] [PDF]
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A. Yoder, X. Wang, Y. Ma, M. T. Philipp, M. Heilbrun, J. H. Weis, C. J. Kirschning, R. M. Wooten, and J. J. Weis Tripalmitoyl-S-Glyceryl-Cysteine-Dependent OspA Vaccination of Toll-Like Receptor 2-Deficient Mice Results in Effective Protection from Borrelia burgdorferi Challenge Infect. Immun., July 1, 2003; 71(7): 3894 - 3900. [Abstract] [Full Text] [PDF]
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I. Diterich, C. Rauter, C. J. Kirschning, and T. Hartung Borrelia burgdorferi-Induced Tolerance as a Model of Persistence via Immunosuppression Infect. Immun., July 1, 2003; 71(7): 3979 - 3987. [Abstract] [Full Text] [PDF]
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H. Crowley and B. T. Huber Host-Adapted Borrelia burgdorferi in Mice Expresses OspA during Inflammation Infect. Immun., July 1, 2003; 71(7): 4003 - 4010. [Abstract] [Full Text] [PDF]
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M. Sato, H. Sano, D. Iwaki, K. Kudo, M. Konishi, H. Takahashi, T. Takahashi, H. Imaizumi, Y. Asai, and Y. Kuroki Direct Binding of Toll-Like Receptor 2 to Zymosan, and Zymosan-Induced NF-{kappa}B Activation and TNF-{alpha} Secretion Are Down-Regulated by Lung Collectin Surfactant Protein A J. Immunol., July 1, 2003; 171(1): 417 - 425. [Abstract] [Full Text] [PDF]
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