title: Defective macrophage handling of Escherichia coli in Crohn's disease.
abstract: OBJECTIVE
  Escherichia coli can be isolated from lamina propria macrophages in Crohn's disease (CD), and their intramacrophage persistence may provide a stimulus for inflammation. To further determine the contributions of macrophage dysfunction and E. coli pathogenicity to this, we aimed to compare in vitro functioning of macrophages from patients with CD and healthy controls (HC) in response to infection with CD-derived adherent-invasive E. coli (AIEC) and less pathogenic E. coli strains.
  
  
  METHODS
  Monocyte-derived macrophages were cultured from patients with CD and HC. Intramacrophage survival of E. coli strains (CD-derived adherent-invasive [AI] and non-AI strains and laboratory strain K-12) was compared. Macrophage cytokine release (tumor necrosis factor alpha [TNFα], interleukin [IL]-23, IL-8 and IL-10) and monocyte phagoctyosis and respiratory burst function were measured after E. coli infection. For CD patients, laboratory data were correlated with clinical phenotype, use of immunomodulation, and CD risk alleles (NOD2, IL-23R, ATG16L1 and IRGM).
  
  
  RESULTS
  Attenuated TNFα and IL-23 release from CD macrophages was found after infection with all E. coli strains. There was prolonged survival of CD-derived AIEC, CD-derived non-AIEC and E. coli K-12 in macrophages from CD patients compared to within those from HC. No abnormality of monocyte phagocytosis or respiratory burst function was detected in CD. Macrophage dysfunction in CD was not influenced by phenotype, use of immunomodulation or genotype.
  
  
  CONCLUSIONS
  CD macrophage responses to infection with E. coli are deficient, regardless of clinical phenotype, CD genotype or E. coli pathogenicity. This suggests host immunodeficiency is an important contributor to intramacrophage E. coli persistence in CD.
authors: Diabetes and Nutritional Sciences Division, King's College London, London, UK.|Department of Gastroenterology, Guy's and St. Thomas' NHS Foundation Trust, St Thomas' Hospital, London, UK.|Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
authors: T R
authors: TR
authors: Elliott
authors: Diabetes and Nutritional Sciences Division, King's College London, London, UK.
authors: B N
authors: BN
authors: Hudspith
authors: Diabetes and Nutritional Sciences Division, King's College London, London, UK.
authors: N B
authors: NB
authors: Rayment
authors: Department of Medical and Molecular Genetics, King's College London School of Medicine, Guy's Hospital London, London, UK.
authors: N J
authors: NJ
authors: Prescott
authors: Diabetes and Nutritional Sciences Division, King's College London, London, UK.
authors: L
authors: L
authors: Petrovska
authors: Diabetes and Nutritional Sciences Division, King's College London, London, UK.
authors: J
authors: J
authors: Hermon-Taylor
authors: Diabetes and Nutritional Sciences Division, King's College London, London, UK.
authors: J
authors: J
authors: Brostoff
authors: Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
authors: A
authors: A
authors: Boussioutas
authors: Department of Medical and Molecular Genetics, King's College London School of Medicine, Guy's Hospital London, London, UK.
authors: C G
authors: CG
authors: Mathew
authors: Diabetes and Nutritional Sciences Division, King's College London, London, UK.|Department of Gastroenterology, Guy's and St. Thomas' NHS Foundation Trust, St Thomas' Hospital, London, UK.
authors: J D
authors: JD
authors: Sanderson
mesh_terms: D000328:Adult; D000483:Alleles; D002478:Cells, Cultured; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology* / Q000382:microbiology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000276:immunology* / Q000472:pathogenicity; D005260:Female; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000382:microbiology; D010587:Phagocytosis / Q000276:immunology; D016897:Respiratory Burst
chemical_list: D016207:Cytokines
keywords: Crohn's disease; Escherichia coli; macrophages; monocytes