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Infect. Immun. doi:10.1128/IAI.00736-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The p50 subunit of NF-B is critical for in vivo clearance of the non-invasive enteric pathogen Citrobacter rodentium

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, UK; Immuno-Inflammation CEDD, GSK Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK; Division of Cell and Molecular Biology, Flowers Building, Imperial College London, Exhibition Road, London SW7 2AZ, UK

^* To whom correspondence should be addressed. Email: siouxsie.wiles{at}imperial.ac.uk.

	Abstract

Citrobacter rodentium, a natural mouse pathogen, belongs to the family of extracellular enteric pathogens that includes enteropathogenic Escherichia coli (EPEC) and enterohaemorrhagic E. coli (EHEC). C. rodentium shares many virulence factors with EPEC and EHEC and relies on attaching and effacing (A/E) lesion formation for colonisation and infection of the gut. In vivo, C. rodentium infection is characterised by increased epithelial cell proliferation, mucosal thickening and a T_H1-type immune response, but with protective immunity believed to be mediated by serum IgG. In this work we have characterised the immune response and pathology of mice lacking the p50 subunit of the transcription factor nuclear factor kappa-B (NF-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 TNF and IFN. 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-kB dependent defences are insufficient to control C. rodentium infection and hence the NF-B p50 subunit is critical for defence against this non-invasive pathogen.