The p50 Subunit of NF-κB Is Critical for In Vivo Clearance of the Noninvasive Enteric PathogenCitrobacter rodentium

• DOI: 10.1128/iai.00736-08
• Publication Date: 2008-08-12T00:43:42Z
• Authors: Alison Dennis; Takahiro Kudo; Laurens Kruidenier; Francis Girard; Valerie F. Crepin; Thomas T. MacDonald; Gad Frankel; Siouxsie Wiles
• Keywords: Mice, Knockout; 0303 health sciences; Enterobacteriaceae Infections; NF-kappa B p50 Subunit; Enzyme-Linked Immunosorbent Assay; Antibodies, Bacterial; Immunohistochemistry; 3. Good health; Mice; 03 medical and health sciences; Immunoglobulin M; Mucociliary Clearance; Immunoglobulin G; Animals; Citrobacter rodentium; Cytokines; Female

ABSTRACTCitrobacter rodentium, a natural mouse pathogen, belongs to the family of extracellular enteric pathogens that includes enteropathogenicEscherichia coli(EPEC) and enterohemorrhagicE. coli(EHEC).C. rodentiumshares 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. rodentiuminfection 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-κB) duringC. rodentiuminfection. We show that p50−/−mice are unable to clearC. rodentiuminfection. 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-CitrobacterIgG and IgM, suggesting that antibody alone is not responsible for bacterial clearance. These data also demonstrate that non-NF-κB-dependent defenses are insufficient to controlC. rodentiuminfection, and hence, the NF-κB p50 subunit is critical for defense against this noninvasive pathogen.