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Infection and Immunity, November 2008, p. 4978-4988, Vol. 76, No. 11
0019-9567/08/$08.00+0     doi:10.1128/IAI.00736-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

The p50 Subunit of NF-{kappa}B Is Critical for In Vivo Clearance of the Noninvasive Enteric Pathogen Citrobacter rodentium{triangledown}

Alison Dennis,1 Takahiro Kudo,1 Laurens Kruidenier,2 Francis Girard,3 Valerie F. Crepin,3 Thomas T. MacDonald,1 Gad Frankel,3 and Siouxsie Wiles3*

Centre for Infectious Disease, Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, 4 Newark Street London E1 2AT, United Kingdom,1 Immuno-Inflammation CEDD, GSK Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, United Kingdom,2 Division of Cell and Molecular Biology, Imperial College London, Flowers Building, Exhibition Road, London SW7 2AZ, United Kingdom3

Received 10 June 2008/ Returned for modification 24 July 2008/ Accepted 1 August 2008

Citrobacter rodentium, a natural mouse pathogen, belongs to the family of extracellular enteric pathogens that includes enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC). C. rodentium shares many virulence factors with EPEC and EHEC and relies on attaching-and-effacing lesion formation for colonization and infection of the gut. In vivo, C. rodentium infection is characterized by increased epithelial cell proliferation, mucosal thickening, and a TH1-type immune response, but with protective immunity believed to be mediated by serum immunoglobulin G (IgG). In this work, we characterize the immune response and pathology of mice lacking the p50 subunit of the transcription factor nuclear factor kappa B (NF-{kappa}B) during C. rodentium infection. We show that p50–/– mice are unable to clear C. rodentium infection. Furthermore, these animals show a reduced influx of immune cells into infected colonic tissue and greater levels of mucosal hyperplasia and the cytokines tumor necrosis factor alpha and gamma interferon. Surprisingly, despite being unable to eliminate infection, p50–/– mice showed markedly higher levels of anti-Citrobacter IgG and IgM, suggesting that antibody alone is not responsible for bacterial clearance. These data also demonstrate that non-NF-{kappa}B-dependent defenses are insufficient to control C. rodentium infection, and hence, the NF-{kappa}B p50 subunit is critical for defense against this noninvasive pathogen.

* Corresponding author. Present address: Department of Infectious Diseases and Immunity, Imperial College London, Commonwealth Building 8N12, Du Cane Road, London W12 0NN, United Kingdom. Phone: 44 (0)20 8383 2730. Fax: 44 (0)20 8383 3394. E-mail: siouxsie.wiles{at}imperial.ac.uk

{triangledown} Published ahead of print on 11 August 2008.

Editor: A. Camilli

Infection and Immunity, November 2008, p. 4978-4988, Vol. 76, No. 11
0019-9567/08/$08.00+0     doi:10.1128/IAI.00736-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Krug, L. T., Collins, C. M., Gargano, L. M., Speck, S. H. (2009). NF-{kappa}B p50 Plays Distinct Roles in the Establishment and Control of Murine Gammaherpesvirus 68 Latency. J. Virol. 83: 4732-4748 [Abstract] [Full Text]  


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