Defective macrophage handling of E scherichia coli in Crohn's disease

Abstract Background and Aim E scherichia coli can be isolated from lamina propria macrophages in C rohn'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 TNF α 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 .