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Review
. 2014:2014:567929.
doi: 10.1155/2014/567929. Epub 2014 Dec 15.

Understanding host-adherent-invasive Escherichia coli interaction in Crohn's disease: opening up new therapeutic strategies

Allison Agus  1 , Sébastien Massier  1 , Arlette Darfeuille-Michaud  2 , Elisabeth Billard  2 , Nicolas Barnich  2
Affiliations
Review

Understanding host-adherent-invasive Escherichia coli interaction in Crohn's disease: opening up new therapeutic strategies

Allison Agus et al. Biomed Res Int. 2014.

Abstract

A trillion of microorganisms colonize the mammalian intestine. Most of them have coevolved with the host in a symbiotic relationship and some of them have developed strategies to promote their replication in the presence of competing microbiota. Recent evidence suggests that perturbation of the microbial community favors the emergence of opportunistic pathogens, in particular adherent-invasive Escherichia coli (AIEC) that can increase incidence and severity of gut inflammation in the context of Crohn's disease (CD). This review will report the importance of AIEC as triggers of intestinal inflammation, focusing on their impact on epithelial barrier function and stimulation of mucosal inflammation. Beyond manipulation of immune response, restoration of gut microbiota as a new treatment option for CD patients will be discussed.

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Figures

Figure 1
Figure 1
Strategies used by AIEC to trigger intestinal inflammation. (1) AIEC are able to strongly adhere to intestinal epithelial cells and colonize gut mucosa using type 1 pili that can bind to mannose residues of CEACAM6, which is overexpressed on the apical surface of ileal epithelial cells in patients with ileal CD. AIEC are also able to adhere to chitinase 3-like-1 receptor (CHI3L1) via the chitin-binding domain of ChiA bacterial protein. AIEC actively resist antimicrobial peptides secreted by Paneth cells. This mechanism involves two genes, arlA, which encodes a Mig-14 family protein implicated in defensin resistance, and arlC, an OmpT family outer membrane protease. (2) AIEC translocation through the epithelial barrier is increased following different mechanisms leading to exacerbation of intestinal inflammation. Modulation of tight junctions (TJs) by AIEC induces paracellular barrier permeability involving ZO-1 redistribution, increased expression of pore-forming claudin-2, and decreased expression of occludin. The endoplasmic reticulum (ER) stress response glycoprotein Gp96 is overexpressed at the apical membrane of ileal epithelial cells in CD patients and acts as a host-receptor for AIEC outer membrane vesicles (OMV) carrying OmpA protein promoting the invasion of the intestinal mucosa. AIEC bacteria interact with Peyer's patches and translocate across M cells via long polar fimbriae (LPF) expression to access lymphoid cells. (3) AIEC intramacrophagic replication is favored in the submucosal compartment of host cells. AIEC intramacrophagic survival could be due to host autophagy defects leading to increased bacterial replication and also enhancing inflammatory responses. AIEC can also induce Th17 and CD8+ cytotoxic responses.
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