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Review
. 2014 Jul 21;20(27):8751-63.
doi: 10.3748/wjg.v20.i27.8751.

Escherichia coli-host macrophage interactions in the pathogenesis of inflammatory bowel disease

Ahmed Tawfik  1 , Paul K Flanagan  1 , Barry J Campbell  1
Affiliations
Review

Escherichia coli-host macrophage interactions in the pathogenesis of inflammatory bowel disease

Ahmed Tawfik et al. World J Gastroenterol. .

Abstract

Multiple studies have demonstrated alterations in the intestinal microbial community (termed the microbiome) in Crohn's disease (CD) and several lines of evidence suggest these changes may have a significant role in disease pathogenesis. In active and quiescent disease, both the faecal and mucosa-associated microbiome are discordant with matched controls with reduced biodiversity, changes in dominant organisms and increased temporal variation described. Mucosa-associated adherent, invasive Escherichia coli (E. coli) (AIEC), pro-inflammatory and resistant to killing by mucosal macrophages, appear to be particularly important. AIEC possess several virulence factors which may confer pathogenic potential in CD. Type-1 pili (FimH) allow adherence to intestinal cells via cell-surface carcinoembryonic antigen-related cell adhesion molecules and possession of long polar fimbrae promotes translocation across the intestinal mucosa via microfold (M)-cells of the follicle-associated epithelium. Resistance to stress genes (htrA, dsbA and hfq) and tolerance of an acidic pH may contribute to survival within the phagolysosomal environment. Here we review the current understanding of the role of mucosa-associated E. coli in Crohn's pathogenesis, the role of the innate immune system, factors which may contribute to prolonged bacterial survival and therapeutic strategies to target intracellular E. coli.

Keywords: Autophagy; Crohn’s disease; Escherichia coli; Inflammatory bowel disease; Intra-macrophage survival and replication; Phagolysosome.

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Figures

Figure 1
Figure 1
Model for the development of Crohn’s disease. AIEC: Adherent, invasive Escherichia coli; ATG16L1: Autophagy-related 16-like 1; CARD15/NOD2: Caspase-recruitment domain 15/nucleotide-binding oligomerization domain-containing-2 receptor; IL-23R: Interleukin-23 receptor; IRGM: Immunity-related GTPase M; LPS: Lipopolysaccharide; NCF4: Neutrophil cytosolic factor-4 gene; PRR: Pathogen recognition receptor; ROS: Reactive oxygen species; TLR4: Toll-like receptor 4.
Figure 2
Figure 2
Patients with Crohn’s disease exhibit reduced bacterial clearance of subcutaneously injected 32P-labelled heat-killed Escherichia coli relative to healthy controls and patients with ulcerative colitis. Reproduced with permission. © 2009 Rockefeller University Press. Originally published in Journal of Experimental Medicine 206: 1883-1897[45]. CD: Crohn’s disease; HC: Healthy controls; UC: Ulcerative colitis.
Figure 3
Figure 3
Crohn’s mucosally associated adherent, invasive Escherichia coli host mucosa interactions: genotype-phenotype relationships. A: Adhesion to, and invasion of intestinal epithelium; B: Mucosal entry across the follicle-associated epithelium; C: Tolerance to stress, habituation and replication within mucosal macrophages. afa: Operon encoding afimbrial adhesin; CEACAM: Carcinoembryonic antigen-related cell adhesion molecule; dsbA: Gene encoding bacterial disulfide oxidoreductase; fimH: Gene encoding bacterial type-1 fimbrial adhesin; gadA-C: Glutamate-dependent acid resistance genes; GP2: Glycoprotein 2 receptor; GP96: Endoplasmic reticulum stress response glycoprotein 96; hfq: Gene encoding RNA-binding host factor essential for replication of the bacteriophage Qβ; htrA: Gene encoding high temperature stress protein A; IECs: Intestinal epithelial cells; lpfA: Gene encoding long polar fimbriae adhesin; M cells: Microfold cells; ompC: Gene encoding outer-membrane vesicle protein C; rpoS/E: Genes encoding stress tolerance sigma factors.
Figure 4
Figure 4
Transmission electron micrograph of adherent, invasive Escherichia coli within macrophages1. A: Crohn’s disease colonic mucosa-associated isolate HM605 surviving and replicating within vesicles of J774-A1 murine macrophages; B: Double membrane around intra-macrophage vesicle indicates bacteria are contained within phagolysosomes (arrow). 1Images courtesy of Dr. Carol L Roberts (University of Liverpool, United Kingdom).
See this image and copyright information in PMC

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