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

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 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 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 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).