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Science 30 July 1999:
Vol. 285. no. 5428, pp. 736 - 739
DOI: 10.1126/science.285.5428.736
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Reports

Cell Activation and Apoptosis by Bacterial Lipoproteins Through Toll-like Receptor-2

Antonios O. Aliprantis, 1* Ruey-Bing Yang, 2* Melanie R. Mark, 2 Shelly Suggett, 3 Brigitte Devaux, 3 Justin D. Radolf, 4 Gary R. Klimpel, 5 Paul Godowski, 2 Arturo Zychlinsky 1dagger

Apoptosis is implicated in the generation and resolution of inflammation in response to bacterial pathogens. All bacterial pathogens produce lipoproteins (BLPs), which trigger the innate immune response. BLPs were found to induce apoptosis in THP-1 monocytic cells through human Toll-like receptor-2 (hTLR2). BLPs also initiated apoptosis in an epithelial cell line transfected with hTLR2. In addition, BLPs stimulated nuclear factor-kappa B, a transcriptional activator of multiple host defense genes, and activated the respiratory burst through hTLR2. Thus, hTLR2 is a molecular link between microbial products, apoptosis, and host defense mechanisms.

1 Skirball Institute and Department of Microbiology, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA.
2 Department of Molecular Biology and
3 Antibody Technology Group, Genentech, South San Francisco, CA 94080, USA.
4 Center for Microbial Pathogenesis, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA.
5 Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: zychlins{at}saturn.med.nyu.edu

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J. C. Setubal, M. Reis, J. Matsunaga, and D. A. Haake (2006)
Microbiology 152, 113-121
   Abstract »    Full Text »    PDF »
Toll-Like Receptor 2 Deficiency Delays Pneumococcal Phagocytosis and Impairs Oxidative Killing by Granulocytes.
M. Letiembre, H. Echchannaoui, P. Bachmann, F. Ferracin, C. Nieto, M. Espinosa, and R. Landmann (2005)
Infect. Immun. 73, 8397-8401
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Proinflammatory Effects of Bacterial Recombinant Human C-Reactive Protein Are Caused by Contamination With Bacterial Products, Not by C-Reactive Protein Itself.
M. B. Pepys, P. N. Hawkins, M. C. Kahan, G. A. Tennent, J. R. Gallimore, D. Graham, C. A. Sabin, A. Zychlinsky, and J. de Diego (2005)
Circ. Res. 97, e97-e103
   Abstract »    Full Text »    PDF »
Domain Exchange between Human Toll-like Receptors 1 and 6 Reveals a Region Required for Lipopeptide Discrimination.
K. O. Omueti, J. M. Beyer, C. M. Johnson, E. A. Lyle, and R. I. Tapping (2005)
J. Biol. Chem. 280, 36616-36625
   Abstract »    Full Text »    PDF »
From the Th1/Th2 Paradigm towards a Toll-Like Receptor/T-Helper Bias.
M. G. Netea, J. W. M. Van der Meer, R. P. Sutmuller, G. J. Adema, and B.-J. Kullberg (2005)
Antimicrob. Agents Chemother. 49, 3991-3996
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The Apoptotic Response to Pneumolysin Is Toll-Like Receptor 4 Dependent and Protects against Pneumococcal Disease.
A. Srivastava, P. Henneke, A. Visintin, S. C. Morse, V. Martin, C. Watkins, J. C. Paton, M. R. Wessels, D. T. Golenbock, and R. Malley (2005)
Infect. Immun. 73, 6479-6487
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A Dipalmitoylated Lipoprotein from Mycoplasma pneumoniae Activates NF-{kappa}B through TLR1, TLR2, and TLR6.
T. Shimizu, Y. Kida, and K. Kuwano (2005)
J. Immunol. 175, 4641-4646
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Regulation of Lipopolysaccharide-Induced Lung Inflammation by Plasminogen Activator Inhibitor-1 through a JNK-Mediated Pathway.
P. G. Arndt, S. K. Young, and G. S. Worthen (2005)
J. Immunol. 175, 4049-4059
   Abstract »    Full Text »    PDF »
Genetic Loci of Major Antigenic Protein Genes of Edwardsiella tarda.
N. Verjan, I. Hirono, and T. Aoki (2005)
Appl. Envir. Microbiol. 71, 5654-5658
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Lipoprotein-Dependent and -Independent Immune Responses to Spirochetal Infection.
J. C. Salazar, C. D. Pope, M. W. Moore, J. Pope, T. G. Kiely, and J. D. Radolf (2005)
Clin. Vaccine Immunol. 12, 949-958
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MyD88, but Not Toll-Like Receptors 4 and 2, Is Required for Efficient Clearance of Brucella abortus.
D. S. Weiss, K. Takeda, S. Akira, A. Zychlinsky, and E. Moreno (2005)
Infect. Immun. 73, 5137-5143
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Direct Stimulation of Human T Cells via TLR5 and TLR7/8: Flagellin and R-848 Up-Regulate Proliferation and IFN-{gamma} Production by Memory CD4+ T Cells.
G. Caron, D. Duluc, I. Fremaux, P. Jeannin, C. David, H. Gascan, and Y. Delneste (2005)
J. Immunol. 175, 1551-1557
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Mycobacterium tuberculosis Regulates CD1 Antigen Presentation Pathways through TLR-2.
C. Roura-Mir, L. Wang, T.-Y. Cheng, I. Matsunaga, C. C. Dascher, S. L. Peng, M. J. Fenton, C. Kirschning, and D. B. Moody (2005)
J. Immunol. 175, 1758-1766
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Pellino3 Is a Novel Upstream Regulator of p38 MAPK and Activates CREB in a p38-dependent Manner.
M. P. Butler, J. A. Hanly, and P. N. Moynagh (2005)
J. Biol. Chem. 280, 27759-27768
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Infection of mature dendritic cells with herpes simplex virus type 1 dramatically reduces lymphoid chemokine-mediated migration.
A. T. Prechtel, N. M. Turza, D. J. Kobelt, J. I. Eisemann, R. S. Coffin, Y. McGrath, C. Hacker, X. Ju, M. Zenke, and A. Steinkasserer (2005)
J. Gen. Virol. 86, 1645-1657
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The expression and roles of Toll-like receptors in the biology of the human neutrophil.
L. C. Parker, M. K. B. Whyte, S. K. Dower, and I. Sabroe (2005)
J. Leukoc. Biol. 77, 886-892
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TLR4, but Not TLR2, Signals Autoregulatory Apoptosis of Cultured Microglia: A Critical Role of IFN-{beta} as a Decision Maker.
D. Y. Jung, H. Lee, B.-Y. Jung, J. Ock, M.-S. Lee, W.-H. Lee, and K. Suk (2005)
J. Immunol. 174, 6467-6476
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Outer Membrane Protein P6 of Nontypeable Haemophilus influenzae Is a Potent and Selective Inducer of Human Macrophage Proinflammatory Cytokines.
C. S. Berenson, T. F. Murphy, C. T. Wrona, and S. Sethi (2005)
Infect. Immun. 73, 2728-2735
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Identification of an Immunomodulating Agent from Mycobacterium leprae.
Y. Maeda, T. Mukai, J. Spencer, and M. Makino (2005)
Infect. Immun. 73, 2744-2750
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Mycobacteria Inhibition of IFN-{gamma} Induced HLA-DR Gene Expression by Up-Regulating Histone Deacetylation at the Promoter Region in Human THP-1 Monocytic Cells.
Y. Wang, H. M. Curry, B. S. Zwilling, and W. P. Lafuse (2005)
J. Immunol. 174, 5687-5694
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Apoptosis Induced by the Toll-Like Receptor Adaptor TRIF Is Dependent on Its Receptor Interacting Protein Homotypic Interaction Motif.
W. J. Kaiser and M. K. Offermann (2005)
J. Immunol. 174, 4942-4952
   Abstract »    Full Text »    PDF »


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