J. Exp. Med., Volume 187, Number 7, April 6, 1998 1069-1079

Yersinia enterocolitica Impairs Activation of Transcription Factor NF-B: Involvement in the Induction of Programmed Cell Death and in the Suppression of the Macrophage Tumor Necrosis Factor  Production

By Klaus Ruckdeschel,^* Suzanne Harb,^* Andreas Roggenkamp, Mathias Hornef, Robert Zumbihl, Stephan Köhler,^* Jürgen Heesemann, and Bruno Rouot^*

From the ^* Institut National de la Santé et de la Recherche Médicale U431, Université Montpellier II, 34095 Montpellier Cedex 05, France; and the  Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, 80336 München, Germany

In this study, we investigated the activity of transcription factor NF-B in macrophages infected with Yersinia enterocolitica. Although triggering initially a weak NF-B signal, Y. enterocolitica inhibited NF-B activation in murine J774A.1 and peritoneal macrophages within 60 to 90 min. Simultaneously, Y. enterocolitica prevented prolonged degradation of the inhibitory proteins IB- and IB- observed by treatment with lipopolysaccharide (LPS) or nonvirulent, plasmid-cured yersiniae. Analysis of different Y. enterocolitica mutants revealed a striking correlation between the abilities of these strains to inhibit NF-B and to suppress the tumor necrosis factor  (TNF-) production as well as to trigger macrophage apoptosis. When NF-B activation was prevented by the proteasome inhibitor MG-132, nonvirulent yersiniae as well as LPS became able to trigger J774A.1 cell apoptosis and inhibition of the TNF- secretion. Y. enterocolitica also impaired the activity of NF-B in epithelial HeLa cells. Although neither Y. enterocolitica nor TNF- could induce HeLa cell apoptosis alone, TNF- provoked apoptosis when activation of NF-B was inhibited by Yersinia infection or by the proteasome inhibitor MG-132. Together, these data demonstrate that Y. enterocolitica suppresses cellular activation of NF-B, which inhibits TNF- release and triggers apoptosis in macrophages. Our results also suggest that Yersinia infection confers susceptibility to programmed cell death to other cell types, provided that the appropriate death signal is delivered.

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• Young, B. M., Young, G. M. (2002). Evidence for Targeting of Yop Effectors by the Chromosomally Encoded Ysa Type III Secretion System of Yersinia enterocolitica. J. Bacteriol. 184: 5563-5571 [Abstract] [Full Text]  
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• Grosdent, N., Maridonneau-Parini, I., Sory, M.-P., Cornelis, G. R. (2002). Role of Yops and Adhesins in Resistance of Yersinia enterocolitica to Phagocytosis. Infect. Immun. 70: 4165-4176 [Abstract] [Full Text]  
• Caamano, J., Hunter, C. A. (2002). NF-{kappa}B Family of Transcription Factors: Central Regulators of Innate and Adaptive Immune Functions. Clin. Microbiol. Rev. 15: 414-429 [Abstract] [Full Text]  
• Tato, C. M., Hunter, C. A. (2002). Host-Pathogen Interactions: Subversion and Utilization of the NF-{kappa}B Pathway during Infection. Infect. Immun. 70: 3311-3317 [Full Text]  
• Denecker, G., Totemeyer, S., Mota, L. J., Troisfontaines, P., Lambermont, I., Youta, C., Stainier, I., Ackermann, M., Cornelis, G. R. (2002). Effect of Low- and High-Virulence Yersinia enterocolitica Strains on the Inflammatory Response of Human Umbilical Vein Endothelial Cells. Infect. Immun. 70: 3510-3520 [Abstract] [Full Text]  
• Gozal, E., Ortiz, L. A., Zou, X., Burow, M. E., Lasky, J. A., Friedman, M. (2002). Silica-Induced Apoptosis in Murine Macrophage . Involvement of Tumor Necrosis Factor-alpha and Nuclear Factor-kappa B Activation. Am. J. Respir. Cell Mol. Bio. 27: 91-98 [Abstract] [Full Text]  
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• Ruckdeschel, K., Richter, K., Mannel, O., Heesemann, J. (2001). Arginine-143 of Yersinia enterocolitica YopP Crucially Determines Isotype-Related NF-kappa B Suppression and Apoptosis Induction in Macrophages. Infect. Immun. 69: 7652-7662 [Abstract] [Full Text]  
• Bantel, H., Sinha, B., Domschke, W., Peters, G., Schulze-Osthoff, K., Janicke, R. U. (2001). {alpha}-Toxin is a mediator of Staphylococcus aureus-induced cell death and activates caspases via the intrinsic death pathway independently of death receptor signaling. J. Cell Biol. 155: 637-648 [Abstract] [Full Text]  
• Jubier-Maurin, V., Boigegrain, R.-A., Cloeckaert, A., Gross, A., Alvarez-Martinez, M.-T., Terraza, A., Liautard, J., Kohler, S., Rouot, B., Dornand, J., Liautard, J. P. (2001). Major Outer Membrane Protein Omp25 of Brucella suis Is Involved in Inhibition of Tumor Necrosis Factor Alpha Production during Infection of Human Macrophages. Infect. Immun. 69: 4823-4830 [Abstract] [Full Text]  
• Lai, X.-H., Golovliov, I., Sjostedt, A. (2001). Francisella tularensis Induces Cytopathogenicity and Apoptosis in Murine Macrophages via a Mechanism That Requires Intracellular Bacterial Multiplication. Infect. Immun. 69: 4691-4694 [Abstract] [Full Text]  
• Ruckdeschel, K., Mannel, O., Richter, K., Jacobi, C. A., Trulzsch, K., Rouot, B., Heesemann, J. (2001). Yersinia Outer Protein P of Yersinia enterocolitica Simultaneously Blocks the Nuclear Factor-{{kappa}}B Pathway and Exploits Lipopolysaccharide Signaling to Trigger Apoptosis in Macrophages. J. Immunol. 166: 1823-1831 [Abstract] [Full Text]  
• Pagliari, L. J., Perlman, H., Liu, H., Pope, R. M. (2000). Macrophages Require Constitutive NF-kappa B Activation To Maintain A1 Expression and Mitochondrial Homeostasis. Mol. Cell. Biol. 20: 8855-8865 [Abstract] [Full Text]  
• Orth, K., Xu, Z., Mudgett, M. B., Bao, Z. Q., Palmer, L. E., Bliska, J. B., Mangel, W. F., Staskawicz, B., Dixon, J. E. (2000). Disruption of Signaling by Yersinia Effector YopJ, a Ubiquitin-Like Protein Protease. Science 290: 1594-1597 [Abstract] [Full Text]  
• FRENCH, N, PETTERSSON, S (2000). Microbe-host interactions in the alimentary tract: the gateway to understanding inflammatory bowel disease. Gut 47: 162-163 [Full Text]  
• Cornelis, G. R. (2000). Molecular and cell biology aspects of plague. Proc. Natl. Acad. Sci. USA 97: 8778-8783 [Abstract] [Full Text]  
• Strobel, E., Heesemann, J., Mayer, G., Peters, J., Müller-Weihrich, S., Emmerling, P. (2000). Bacteriological and Serological Findings in a Further Case of Transfusion-Mediated Yersinia enterocolitica Sepsis. J. Clin. Microbiol. 38: 2788-2790 [Abstract] [Full Text]  
• Ledru, E., Christeff, N., Patey, O., de Truchis, P., Melchior, J.-C., Gougeon, M.-L. (2000). Alteration of tumor necrosis factor-alpha T-cell homeostasis following potent antiretroviral therapy: contribution to the development of human immunodeficiency virus-associated lipodystrophy syndrome. Blood 95: 3191-3198 [Abstract] [Full Text]  
• Clarkson, R. W. E., Heeley, J. L., Chapman, R., Aillet, F., Hay, R. T., Wyllie, A., Watson, C. J. (2000). NF-kappa B Inhibits Apoptosis in Murine Mammary Epithelia. J. Biol. Chem. 275: 12737-12742 [Abstract] [Full Text]  
• Zhao, Y.-X., Lajoie, G., Zhang, H., Chiu, B., Payne, U., Inman, R. D. (2000). Tumor Necrosis Factor Receptor p55-Deficient Mice Respond to Acute Yersinia enterocolitica Infection with Less Apoptosis and More Effective Host Resistance. Infect. Immun. 68: 1243-1251 [Abstract] [Full Text]  
• Hein, J., Kempf, V. A. J., Diebold, J., Bucheler, N., Preger, S., Horak, I., Sing, A., Kramer, U., Autenrieth, I. B. (2000). Interferon Consensus Sequence Binding Protein Confers Resistance against Yersinia enterocolitica. Infect. Immun. 68: 1408-1417 [Abstract] [Full Text]  
• Fields, K. A., Nilles, M. L., Cowan, C., Straley, S. C. (1999). Virulence Role of V Antigen of Yersinia pestis at the Bacterial Surface. Infect. Immun. 67: 5395-5408 [Abstract] [Full Text]  
• Orth, K., Palmer, L. E., Bao, Z. Q., Stewart, S., Rudolph, A. E., Bliska, J. B., Dixon, J. E. (1999). Inhibition of the Mitogen-Activated Protein Kinase Kinase Superfamily by a Yersinia Effector. Science 285: 1920-1923 [Abstract] [Full Text]  
• Fields, K. A., Straley, S. C. (1999). LcrV of Yersinia pestis Enters Infected Eukaryotic Cells by a Virulence Plasmid-Independent Mechanism. Infect. Immun. 67: 4801-4813 [Abstract] [Full Text]  
• Elewaut, D., DiDonato, J. A., Mogg Kim, J., Truong, F., Eckmann, L., Kagnoff, M. F. (1999). NF-{kappa}B Is a Central Regulator of the Intestinal Epithelial Cell Innate Immune Response Induced by Infection with Enteroinvasive Bacteria. J. Immunol. 163: 1457-1466 [Abstract] [Full Text]  
• Crane, J. K., Majumdar, S., Pickhardt, D. F. III (1999). Host Cell Death due to Enteropathogenic Escherichia coli Has Features of Apoptosis. Infect. Immun. 67: 2575-2584 [Abstract] [Full Text]  
• Palmer, L. E., Pancetti, A. R., Greenberg, S., Bliska, J. B. (1999). YopJ of Yersinia spp. Is Sufficient To Cause Downregulation of Multiple Mitogen-Activated Protein Kinases in Eukaryotic Cells. Infect. Immun. 67: 708-716 [Abstract] [Full Text]  
• Monack, D. M., Mecsas, J., Bouley, D., Falkow, S. (1998). Yersinia-induced Apoptosis In Vivo Aids in the Establishment of a Systemic Infection of Mice. J. Exp. Med. 188: 2127-2137 [Abstract] [Full Text]  
• Rescigno, M., Martino, M., Sutherland, C. L., Gold, M. R., Ricciardi-Castagnoli, P. (1998). Dendritic Cell Survival and Maturation Are Regulated by Different Signaling Pathways. J. Exp. Med. 188: 2175-2180 [Abstract] [Full Text]  
• Cornelis, G. R., Boland, A., Boyd, A. P., Geuijen, C., Iriarte, M., Neyt, C., Sory, M.-P., Stainier, I. (1998). The Virulence Plasmid of Yersinia, an Antihost Genome. Microbiol. Mol. Biol. Rev. 62: 1315-1352 [Abstract] [Full Text]  
• Denecker, G., Declercq, W., Geuijen, C. A. W., Boland, A., Benabdillah, R., van Gurp, M., Sory, M.-P., Vandenabeele, P., Cornelis, G. R. (2001). Yersinia enterocolitica YopP-induced Apoptosis of Macrophages Involves the Apoptotic Signaling Cascade Upstream of Bid. J. Biol. Chem. 276: 19706-19714 [Abstract] [Full Text]  

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