title: Lamina propria macrophage phenotypes in relation to Escherichia coli in Crohn's disease.
abstract: BACKGROUND
  Abnormal handling of E. coli by lamina propria (LP) macrophages may contribute to Crohn's disease (CD) pathogenesis. We aimed to determine LP macrophage phenotypes in CD, ulcerative colitis (UC) and healthy controls (HC), and in CD, to compare macrophage phenotypes according to E. coli carriage.
  
  
  METHODS
  Mucosal biopsies were taken from 35 patients with CD, 9 with UC and 18 HCs. Laser capture microdissection was used to isolate E. coli-laden and unladen LP macrophages from ileal or colonic biopsies. From these macrophages, mRNA was extracted and cytokine and activation marker expression measured using RT-qPCR.
  
  
  RESULTS
  E. coli-laden LP macrophages were identified commonly in mucosal biopsies from CD patients (25/35, 71 %), rarely in UC (1/9, 11 %) and not at all in healthy controls (0/18). LP macrophage cytokine mRNA expression was greater in CD and UC than healthy controls. In CD, E. coli-laden macrophages expressed high IL-10 & CD163 and lower TNFα, IL-23 & iNOS irrespective of macroscopic inflammation. In inflamed tissue, E. coli-unladen macrophages expressed high TNFα, IL-23 & iNOS and lower IL-10 & CD163. In uninflamed tissue, unladen macrophages had low cytokine mRNA expression, closer to that of healthy controls.
  
  
  CONCLUSIONS
  In CD, intra-macrophage E. coli are commonly found and LP macrophages express characteristic cytokine mRNA profiles according to E. coli carriage. Persistence of E. coli within LP macrophages may provide a stimulus for chronic inflammation.
authors.affiliation: Diabetes and Nutritional Sciences Division, King's College London, Franklin Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK. elliott_timothy@hotmail.com.|Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, St Thomas' Hospital, London, SE1 7EH, UK. elliott_timothy@hotmail.com.|Department of Medicine, University of Melbourne, Melbourne, Australia. elliott_timothy@hotmail.com.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Elliott
authors.affiliation: Diabetes and Nutritional Sciences Division, King's College London, Franklin Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK. neil.rayment@kcl.ac.uk.
authors.forename: Neil B
authors.initials: NB
authors.lastname: Rayment
authors.affiliation: Diabetes and Nutritional Sciences Division, King's College London, Franklin Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK. barry.hudspith@kcl.ac.uk.
authors.forename: Barry N
authors.initials: BN
authors.lastname: Hudspith
authors.affiliation: Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Whitechapel, London, E1 1BB, UK. r.e.hands@qmul.ac.uk.
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Hands
authors.affiliation: Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, St Thomas' Hospital, London, SE1 7EH, UK. kirstin.taylor@kcl.ac.uk.|Department of Medical and Molecular Genetics, King's College London School of Medicine, Guy's Hospital, London, SE1 9RT, UK. kirstin.taylor@kcl.ac.uk.
authors.forename: Kirstin
authors.initials: K
authors.lastname: Taylor
authors.affiliation: Diabetes and Nutritional Sciences Division, King's College London, Franklin Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK. gareth.parkes@kcl.ac.uk.|Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, St Thomas' Hospital, London, SE1 7EH, UK. gareth.parkes@kcl.ac.uk.
authors.forename: Gareth C
authors.initials: GC
authors.lastname: Parkes
authors.affiliation: Department of Medical and Molecular Genetics, King's College London School of Medicine, Guy's Hospital, London, SE1 9RT, UK. natalie.prescott@kcl.ac.uk.
authors.forename: Natalie J
authors.initials: NJ
authors.lastname: Prescott
authors.affiliation: Diabetes and Nutritional Sciences Division, King's College London, Franklin Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK. Liljana.petrovska@ahvla.gsi.gov.uk.
authors.forename: Liljana
authors.initials: L
authors.lastname: Petrovska
authors.affiliation: Diabetes and Nutritional Sciences Division, King's College London, Franklin Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK. j.hermon@kcl.ac.uk.
authors.forename: John
authors.initials: J
authors.lastname: Hermon-Taylor
authors.affiliation: Diabetes and Nutritional Sciences Division, King's College London, Franklin Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK. j.brostoff@virgin.net.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Brostoff
authors.affiliation: Department of Medicine, University of Melbourne, Melbourne, Australia. alexb@unimelb.edu.au.
authors.forename: Alex
authors.initials: A
authors.lastname: Boussioutas
authors.affiliation: Department of Medical and Molecular Genetics, King's College London School of Medicine, Guy's Hospital, London, SE1 9RT, UK. christopher.mathew@kcl.ac.uk.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Mathew
authors.affiliation: Postgraduate Medical Institute, Faculty of Medical Science, Anglia Ruskin University, Chelmsford, Essex, UK. stephen.bustin@anglia.ac.uk.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Bustin
authors.affiliation: Diabetes and Nutritional Sciences Division, King's College London, Franklin Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK. jeremy.sanderson@kcl.ac.uk.|Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, St Thomas' Hospital, London, SE1 7EH, UK. jeremy.sanderson@kcl.ac.uk.
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Sanderson
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000276:immunology / Q000382:microbiology; D003424:Crohn Disease / Q000276:immunology* / Q000382:microbiology; D016207:Cytokines / Q000378:metabolism; D004926:Escherichia coli / Q000276:immunology* / Q000302:isolation & purification; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype
chemical_list: D015415:Biomarkers; D016207:Cytokines