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

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

Core tip: There is significant evidence implicating adherent, invasive mucosa-associated Escherichia coli (AIEC) in the pathogenesis of Crohn’s disease. AIEC translocate M-cells of Peyer’s patches and lymphoid follicles of the colon, and then to survive and replicate within underlying mucosal macrophages. How Crohn’s AIEC resist killing and adapt to the environment within the phagolysosme to survive and grow within macrophages is still poorly understood. Here we review the current understanding of the role of AIEC 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 AIEC.