title: Escherichia coli-host macrophage interactions in the pathogenesis of inflammatory bowel disease.
abstract: Multiple studies have demonstrated alterations in the intestinal microbial community (termed the microbiome) in Crohn's disease (CD) and several lines of evidence suggest these changes may have a significant role in disease pathogenesis. In active and quiescent disease, both the faecal and mucosa-associated microbiome are discordant with matched controls with reduced biodiversity, changes in dominant organisms and increased temporal variation described. Mucosa-associated adherent, invasive Escherichia coli (E. coli) (AIEC), pro-inflammatory and resistant to killing by mucosal macrophages, appear to be particularly important. AIEC possess several virulence factors which may confer pathogenic potential in CD. Type-1 pili (FimH) allow adherence to intestinal cells via cell-surface carcinoembryonic antigen-related cell adhesion molecules and possession of long polar fimbrae promotes translocation across the intestinal mucosa via microfold (M)-cells of the follicle-associated epithelium. Resistance to stress genes (htrA, dsbA and hfq) and tolerance of an acidic pH may contribute to survival within the phagolysosomal environment. Here we review the current understanding of the role of mucosa-associated E. coli in Crohn's pathogenesis, the role of the innate immune system, factors which may contribute to prolonged bacterial survival and therapeutic strategies to target intracellular E. coli.
authors.affiliation: Ahmed Tawfik, Paul K Flanagan, Barry J Campbell, Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, United Kingdom.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Tawfik
authors.affiliation: Ahmed Tawfik, Paul K Flanagan, Barry J Campbell, Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, United Kingdom.
authors.forename: Paul K
authors.initials: PK
authors.lastname: Flanagan
authors.affiliation: Ahmed Tawfik, Paul K Flanagan, Barry J Campbell, Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, United Kingdom.
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Campbell
mesh_terms: D000818:Animals; D001343:Autophagy; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology / Q000382:microbiology* / Q000628:therapy; D004926:Escherichia coli / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity*; D005243:Feces / Q000382:microbiology; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology; D007422:Intestines / Q000276:immunology / Q000382:microbiology*; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D064307:Microbiota; D037521:Virulence Factors / Q000235:genetics / Q000276:immunology
chemical_list: D037521:Virulence Factors
keywords: Autophagy; Crohn’s disease; Escherichia coli; Inflammatory bowel disease; Intra-macrophage survival and replication; Phagolysosome
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