Details

Autor(en) / Beteiligte

• Elliott, TR
• Hudspith, BN
• Rayment, NB
• Prescott, NJ
• Petrovska, L
• Hermon-Taylor, J
• Brostoff, J
• Boussioutas, A
• Mathew, CG
• Sanderson, JD

Titel

Defective macrophage handling of Escherichia coli in Crohn's disease

Ist Teil von

• Journal of gastroenterology and hepatology, 2015-08, Vol.30 (8), p.1265-1274

Ort / Verlag

Australia: Blackwell Publishing Ltd

Erscheinungsjahr

2015

Link zum Volltext

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• Background and Aim  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] and non‐AI strains and laboratory strain K‐12) was compared. Macrophage cytokine release (tumor necrosis factor alpha [TNFα], interleukin [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.