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

Elliott TR, Rayment NB, Hudspith BN, Hands RE, Taylor K, Parkes GC, Prescott NJ, Petrovska L, Hermon-Taylor J, Brostoff J, Boussioutas A, Mathew CG, Bustin SA, Sanderson JD - BMC Gastroenterol (2015)

Bottom Line: In inflamed tissue, E. coli-unladen macrophages expressed high TNFα, IL-23 & iNOS and lower IL-10 & CD163.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.

View Article: PubMed Central - PubMed

Affiliation: Diabetes and Nutritional Sciences Division, King's College London, Franklin Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK. elliott_timothy@hotmail.com.

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.

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.

No MeSH data available.


Related in: MedlinePlus

Higher median endoscopic severity score for CD patients with E. coli-laden LP macrophages compared with those without E. coli-laden LP macrophages at biopsy (P < .001, Mann-Whitney test). SES-CD; simplified endoscopic score for Crohn’s disease, Mø; macrophages
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Fig2: Higher median endoscopic severity score for CD patients with E. coli-laden LP macrophages compared with those without E. coli-laden LP macrophages at biopsy (P < .001, Mann-Whitney test). SES-CD; simplified endoscopic score for Crohn’s disease, Mø; macrophages

Mentions: E. coli-laden macrophages were commonly identified in mucosal biopsies from CD patients (25/35 (71 %)), rarely in UC (1/9 (11 %)) and were not present in any of 18 healthy controls (Table 3). The presence of E. coli-laden macrophages in CD correlated with endoscopic severity (P < .001) (Fig. 2) but not with other clinical or demographic factors (age, gender, smoking status, disease location, immunomodulation or site of biopsy - data not shown). Six of the 35 CD patients had paired biopsies taken from macroscopically inflamed and uninflamed mucosa. In these 6 patients, E. coli-laden LP macrophages were present in 6/6 inflamed and 3/6 uninflamed biopsies respectively.Fig. 2


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

Elliott TR, Rayment NB, Hudspith BN, Hands RE, Taylor K, Parkes GC, Prescott NJ, Petrovska L, Hermon-Taylor J, Brostoff J, Boussioutas A, Mathew CG, Bustin SA, Sanderson JD - BMC Gastroenterol (2015)

Higher median endoscopic severity score for CD patients with E. coli-laden LP macrophages compared with those without E. coli-laden LP macrophages at biopsy (P < .001, Mann-Whitney test). SES-CD; simplified endoscopic score for Crohn’s disease, Mø; macrophages
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4490755&req=5

Fig2: Higher median endoscopic severity score for CD patients with E. coli-laden LP macrophages compared with those without E. coli-laden LP macrophages at biopsy (P < .001, Mann-Whitney test). SES-CD; simplified endoscopic score for Crohn’s disease, Mø; macrophages
Mentions: E. coli-laden macrophages were commonly identified in mucosal biopsies from CD patients (25/35 (71 %)), rarely in UC (1/9 (11 %)) and were not present in any of 18 healthy controls (Table 3). The presence of E. coli-laden macrophages in CD correlated with endoscopic severity (P < .001) (Fig. 2) but not with other clinical or demographic factors (age, gender, smoking status, disease location, immunomodulation or site of biopsy - data not shown). Six of the 35 CD patients had paired biopsies taken from macroscopically inflamed and uninflamed mucosa. In these 6 patients, E. coli-laden LP macrophages were present in 6/6 inflamed and 3/6 uninflamed biopsies respectively.Fig. 2

Bottom Line: In inflamed tissue, E. coli-unladen macrophages expressed high TNFα, IL-23 & iNOS and lower IL-10 & CD163.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.

View Article: PubMed Central - PubMed

Affiliation: Diabetes and Nutritional Sciences Division, King's College London, Franklin Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK. elliott_timothy@hotmail.com.

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.

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.

No MeSH data available.


Related in: MedlinePlus