Lamina propria macrophage phenotypes in relation to Escherichia coli in Crohn’s disease

BMC Gastroenterology

Research Article

Rebecca E. Hands¹  Kirstin Taylor²  Christopher G. Mathew³  Natalie J. Prescott³  Alex Boussioutas⁴  Jonathan Brostoff⁵  Neil B. Rayment⁵  John Hermon-Taylor⁵  Barry N. Hudspith⁵  Liljana Petrovska⁵  Gareth C. Parkes⁶  Jeremy D. Sanderson⁶  Timothy R. Elliott⁷  Stephen A. Bustin⁸ 

[1] Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Whitechapel, E1 1BB, London, UK;Department of Gastroenterology, Guy’s and St Thomas’ NHS Foundation Trust, St Thomas’ Hospital, SE1 7EH, London, UK;Department of Medical and Molecular Genetics, King’s College London School of Medicine, Guy’s Hospital, SE1 9RT, London, UK;Department of Medical and Molecular Genetics, King’s College London School of Medicine, Guy’s Hospital, SE1 9RT, London, UK;Department of Medicine, University of Melbourne, Melbourne, Australia;Diabetes and Nutritional Sciences Division, King’s College London, Franklin Wilkins Building, 150 Stamford Street, SE1 9NH, London, UK;Diabetes and Nutritional Sciences Division, King’s College London, Franklin Wilkins Building, 150 Stamford Street, SE1 9NH, London, UK;Department of Gastroenterology, Guy’s and St Thomas’ NHS Foundation Trust, St Thomas’ Hospital, SE1 7EH, London, UK;Diabetes and Nutritional Sciences Division, King’s College London, Franklin Wilkins Building, 150 Stamford Street, SE1 9NH, London, UK;Department of Gastroenterology, Guy’s and St Thomas’ NHS Foundation Trust, St Thomas’ Hospital, SE1 7EH, London, UK;Department of Medicine, University of Melbourne, Melbourne, Australia;Postgraduate Medical Institute, Faculty of Medical Science, Anglia Ruskin University, Chelmsford, Essex, UK;

关键词: Crohn’s disease;    Escherichia coli;    Macrophages;   

DOI  :  10.1186/s12876-015-0305-3

 received in 2015-01-22, accepted in 2015-06-18,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundAbnormal 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.MethodsMucosal 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.ResultsE. 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.ConclusionIn 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.

【 授权许可】

CC BY   
© Elliott et al. 2015