Abstract
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.
Highlights
Abnormal handling of E. coli by lamina propria (LP) macrophages may contribute to Crohn’s disease (CD) pathogenesis
Prevalence of E. coli-laden LP macrophages in CD, ulcerative colitis (UC) and healthy controls 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)
Intra-macrophage E. coli in CD We found that E. coli can be identified within LP macrophages in most CD patients using immunohistochemistry with an anti-E. coli specific polyclonal antibody
Summary
Abnormal handling of E. coli by lamina propria (LP) macrophages may contribute to Crohn’s disease (CD) pathogenesis. One broad classification distinguishes M1 inflammatory macrophages, which express high IL-12, iNOS and low IL-10, from M2 regulatory macrophages. Elliott et al BMC Gastroenterology (2015) 15:75 which express high IL-10 and low IL-12 [14]. In diseases such as atherosclerosis and malignancy, these polarised macrophage phenotypes make particular contributions to pathogenesis [14]. In CD, lamina propria macrophages are more numerous, probably due to recruitment of CD14+ monocytes, and have greater pro-inflammatory cytokine expression [16]. The roles of differing macrophage phenotypes in CD pathogenesis are incompletely understood
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