title: Enteric infection with Citrobacter rodentium induces coagulative liver necrosis and hepatic inflammation prior to peak infection and colonic disease.
abstract: Acute and chronic forms of inflammation are known to affect liver responses and susceptibility to disease and injury. Furthermore, intestinal microbiota has been shown critical in mediating inflammatory host responses in various animal models. Using C. rodentium, a known enteric bacterial pathogen, we examined liver responses to gastrointestinal infection at various stages of disease pathogenesis. For the first time, to our knowledge, we show distinct liver pathology associated with enteric infection with C. rodentium in C57BL/6 mice, characterized by increased inflammation and hepatitis index scores as well as prominent periportal hepatocellular coagulative necrosis indicative of thrombotic ischemic injury in a subset of animals during the early course of C. rodentium pathogenesis. Histologic changes in the liver correlated with serum elevation of liver transaminases, systemic and liver resident cytokines, as well as signal transduction changes prior to peak bacterial colonization and colonic disease. C. rodentium infection in C57BL/6 mice provides a potentially useful model to study acute liver injury and inflammatory stress under conditions of gastrointestinal infection analogous to enteropathogenic E. coli infection in humans.
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America. raczynsa@gmail.com
authors.forename: Arkadiusz R
authors.initials: AR
authors.lastname: Raczynski
authors.forename: Sureshkumar
authors.initials: S
authors.lastname: Muthupalani
authors.forename: Katherine
authors.initials: K
authors.lastname: Schlieper
authors.forename: James G
authors.initials: JG
authors.lastname: Fox
authors.forename: Steven R
authors.initials: SR
authors.lastname: Tannenbaum
authors.forename: David B
authors.initials: DB
authors.lastname: Schauer
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D018925:Chemokines / Q000097:blood; D044082:Citrobacter rodentium; D003108:Colonic Diseases / Q000382:microbiology*; D016207:Cytokines / Q000097:blood; D006505:Hepatitis / Q000382:microbiology*; D015151:Immunoblotting; D007150:Immunohistochemistry; D008099:Liver / Q000382:microbiology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis / Q000382:microbiology; D015398:Signal Transduction / Q000502:physiology*; D018709:Statistics, Nonparametric
chemical_list: D018925:Chemokines; D016207:Cytokines