Citrobacter rodentium infection causes iNOS-independent intestinal epithelial dysfunction in mice.
Attaching-effacing bacteria are major causes of infectious diarrhea in humans worldwide. Citrobacter rodentium is an attaching-effacing enteric pathogen that causes transmissible murine colonic mucosal hyperplasia. We characterized colonic inflammation and ion transport at 3, 7, 10, 30, and 60 d after infection of C57Bl/6 mice with C. rodentium. Macroscopic damage score was significantly increased 7 and 10 d after infection. Colonic wall thickness was increased at 7, 10, 30, and 60 d. Myeloperoxidase (MPO) activity was significantly increased at 3, 7, and 10 d and returned to control levels by days 30 and 60. The expressions of inducible nitric oxide synthase and cyclooxygenase-2 were increased by C. rodentium infection. Significant reductions in the epithelial secretory response to carbachol, but not to electrical field stimulation or forskolin, were observed at 3 and 10 d of infection. Translocation of enteric bacteria into the mesenteric lymph nodes was observed 10 d following infection. There was no difference in response to infection between animals deficient in inducible nitric oxide synthase and wild-type controls. The COX-2 inhibitor rofecoxib caused decreased wall thickness and MPO activity at day 10. However, COX-2 inhibition did not alter infection-induced changes in ion transport. Citrobacter rodentium infection causes colonic inflammation, mucosal hyperplasia, and nitric-oxide-independent epithelial dysfunction in association with increased permeability to luminal bacteria.
Skinn
Andrew C
AC
Mucosal Inflammation Research Group and Department of Physiology and Biophysics, University of Calgary, 3330 Hospital Dr NW, Calgary, AB T2N 4N1, Canada.
Vergnolle
Nathalie
N
Zamuner
Stella R
SR
Wallace
John L
JL
Cellars
Laurie
L
MacNaughton
Wallace K
WK
Sherman
Philip M
PM
D000818:Animals; D018988:Bacterial Translocation; D002217:Carbachol / Q000494:pharmacology; D002463:Cell Membrane Permeability; D018679:Cholinergic Agonists / Q000494:pharmacology; D044082:Citrobacter rodentium; D003092:Colitis / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D003106:Colon / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004756:Enterobacteriaceae Infections / Q000150:complications / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D006965:Hyperplasia; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology; D007419:Intestinal Secretions / Q000378:metabolism; D017136:Ion Transport; D007783:Lactones / Q000494:pharmacology; D008198:Lymph Nodes / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D013450:Sulfones / Q000494:pharmacology; D013997:Time Factors
D018679:Cholinergic Agonists; D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; D002217:Carbachol; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2