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

BMC Gastroenterology

Jeremy D. Sanderson³  Stephen A. Bustin²  Christopher G. Mathew⁵  Alex Boussioutas⁴  Jonathan Brostoff¹  John Hermon-Taylor¹  Liljana Petrovska¹  Natalie J. Prescott⁵  Gareth C. Parkes³  Kirstin Taylor⁵  Rebecca E. Hands⁶  Barry N. Hudspith¹  Neil B. Rayment¹  Timothy R. Elliott⁴ 

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

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

Others  :  1223125
DOI  :  10.1186/s12876-015-0305-3

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

【 摘 要 】

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.

Conclusion

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.

【 授权许可】

   
2015 Elliott et al.

【 图 表 】

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