title: Distinct inflammatory and cytopathic characteristics of Escherichia coli isolates from inflammatory bowel disease patients.
abstract: Escherichia coli (E. coli) may be implicated in the pathogenesis of inflammatory bowel disease (IBD), as implied from a higher prevalence of mucosa-associated E. coli in the gut of IBD-affected individuals. However, it is unclear whether different non-diarrheagenic E. coli spp. segregate from each other in their ability to promote intestinal inflammation. Herein we compared the inflammation-inducing properties of non-diarrheagenic LF82, 691-04A, E. coli Nissle 1917 (ECN) and eleven new intestinal isolates from different locations in five IBD patients and one healthy control. Viable E. coli were cultured with human monocyte-derived dendritic cells (moDCs) and monolayers of intestinal epithelial cells (IECs), followed by analysis of secreted cytokines, intracellular levels of reactive oxygen species and cellular death. The IBD-associated E. coli LF82 induced the same dose-dependent inflammatory cytokine profile as ECN and ten of the new E. coli isolates displayed as high level IL-12p70, IL-1β, IL-23 and TNF-α from moDCs irrespective of their site of isolation (ileum/colon/faeces), disease origin (diseased/non-diseased) or known virulence factors. Contrarily, 691-04A and one new IBD E. coli isolate induced a different cellular phenotype with enhanced killing of moDCs and IECs, coupled to elevated IL-18. The cytopathic nature of 691-04A and one other IBD E. coli isolate suggests that colonization with specific non-diarrheagenic E. coli could promote intestinal barrier leakage and profound intestinal inflammation, while LF82, ECN and the remaining non-diarrheagenic E. coli isolates hold notorious pro-inflammatory characteristics that can progress inflammation in case of intestinal barrier leakage.
authors.affiliation: Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Denmark.
authors.forename: Stina Rikke
authors.initials: SR
authors.lastname: Jensen
authors.affiliation: Department of Microbiology and Infection Control, Statens Serum Institut, Denmark.
authors.forename: Hengameh Chloé
authors.initials: HC
authors.lastname: Mirsepasi-Lauridsen
authors.affiliation: Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Denmark.
authors.forename: Anna Hammerich
authors.initials: AH
authors.lastname: Thysen
authors.affiliation: Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Denmark.
authors.forename: Jørn
authors.initials: J
authors.lastname: Brynskov
authors.affiliation: Department of Microbiology and Infection Control, Statens Serum Institut, Denmark.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Krogfelt
authors.affiliation: Department of Gastroenterology, Medical Section, Hvidovre Hospital, University of Copenhagen, Denmark; Department of Clinical Microbiology, Hvidovre Hospital, University of Copenhagen, Denmark.
authors.forename: Andreas Munk
authors.initials: AM
authors.lastname: Petersen
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Denmark.
authors.forename: Anders Elm
authors.initials: AE
authors.lastname: Pedersen
authors.affiliation: Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Denmark. Electronic address: sbp@bio.dtu.dk.
authors.forename: Susanne
authors.initials: S
authors.lastname: Brix
mesh_terms: D016923:Cell Death; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D004926:Escherichia coli / Q000302:isolation & purification* / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000150:complications* / Q000382:microbiology*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000150:complications*; D017382:Reactive Oxygen Species / Q000032:analysis
chemical_list: D016207:Cytokines; D017382:Reactive Oxygen Species
keywords: Cell death; Cytokine profile; Dendritic cells; IBD-associated E. coli; Inflammation