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Defective macrophage handling of Escherichia coli in Crohn's disease

Research output: Contribution to journalArticlepeer-review

Original languageEnglish
JournalJournal of Gastroenterology and Hepatology
Early online date23 Mar 2015
DOIs
E-pub ahead of print23 Mar 2015
Published2015

King's Authors

Abstract

BACKGROUND: Escherichia coli can be isolated from lamina propria macrophages in Crohn's disease (CD) and their intramacrophage persistence may provide a stimulus for inflammation. To further determine the contributions of macrophage dysfunction and E. coli pathogenicity to this, we aimed to compare in vitro functioning of macrophages from patients with CD and healthy controls (HC) in response to infection with CD-derived adherent-invasive E. coli (AIEC) and less pathogenic E. coli strains.

METHODS: Monocyte-derived macrophages were cultured from patients with CD and HC. Intramacrophage survival of E. coli strains (CD-derived adherent-invasive (AI) & non-AI strains and laboratory strain K-12) was compared. Macrophage cytokine release (TNFα, IL-23, IL-8 and IL-10) and monocyte phagoctyosis and respiratory burst function were measured after E. coli infection. For CD patients, laboratory data were correlated with clinical phenotype, use of immunomodulation and CD risk alleles (NOD2, IL-23R, ATG16L1 and IRGM).

RESULTS: Attenuated TNFα and IL-23 release from CD macrophages was found after infection with all E. coli strains. There was prolonged survival of CD-derived AIEC, CD-derived non-AIEC and E. coli K-12 in macrophages from CD patients compared to within those from HC. No abnormality of monocyte phagocytosis or respiratory burst function was detected in CD. Macrophage dysfunction in CD was not influenced by phenotype, use of immunomodulation or genotype.

CONCLUSIONS: CD macrophage responses to infection with E. coli are deficient, regardless of clinical phenotype, CD genotype or E. coli pathogenicity. This suggests host immunodeficiency is an important contributor to intramacrophage E. coli persistence in CD.

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