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Press Info item. 05/05/2011

Precisely targeted infection

Colonisation by Escherichia coli bacteria of specific structures in the intestinal epithelium, Peyer's patches, may be at the origin of the onset of Crohn's disease. This is the conclusion of a study carried out by researchers from INRA and the Université d’Auvergne. This targeted infection is rendered possible by the expression of filaments that allow bacterial adhesion to immune system structures present in the intestinal mucosa. This work opens the way to new therapeutic possibilities that would consist in blocking this early stage of the infective process. These results were published in "The Journal of Clinical Investigation" in March 2011.

A chronic inflammatory disease of the intestine, Crohn's disease results in a hyperactive state of the intestinal immune system. Clinical and epidemiological studies have been able to demonstrate the involvement of environmental, genetic and infectious factors in this disease. Thus, in terms of infective factors, it can be noted that the intestinal mucosa of the terminal small intestine (ileum) in Crohn's disease patients is abnormally colonised by a particular group of pathogenic Escherichia coli bacteria called Adherent-Invasive E. coli (AIEC). These are able to adhere to, and then invade, the cells of the intestinal mucosa. Early lesions of Crohn's disease tend to appear in Peyer's patches, immune system structures that are mainly found in the small intestine and which permit presentation to the immune system of antigens or bacteria present in the digestive tract lumen. For this reason, a team of scientists in an INRA-Université d’Auvergne research unit focused on AIEC in order to test the hypothesis according to which they might massively target Peyer's patches and thus be responsible for early-stage intestinal lesions.

For this purpose, the researchers analysed the genome sequence of a reference strain in the AIEC group of Escherichia coli. This analysis demonstrated a series of genes (called the lpf operon) which allowed the expression of filaments that facilitate the adherence of bacteria to specialised host cells, the "Long Polar Fimbriae (LPF)". The latter thus constitute a factor for bacterial virulence. And indeed, AEIC bacteria possessing this series of genes were present in 22% of Crohn's disease patients, versus 3% of control subjects. Furthermore, if the scientists inactivated this operon, the interaction of AIEC bacteria with mouse and human Peyer's patches diminished markedly. The intestinal epithelium associated with Peyer's patches is characterised by the presence of M cells which are implicated in the presentation of antigens to the immune system. The presence of filaments allows the AIEC bacteria to interact with the M cells and pass through a layer of these cells.

Alongside the results described previously, the scientists in this research unit also analysed the importance of mutations in the susceptibility genes associated with Crohn's disease, such as the nod2 gene. A study in animals not expressing the nod2 gene showed an increase in the number of M cells in Peyer's patches, leading to an increase in AEIC bacteria in these patches.

This study thus made it possible to demonstrate the involvement of filaments (long polar fimbriae) in the targeting of Peyer's patches by AIEC E. coli bacteria. This suggests that the infection of patients who are genetically predisposed to Crohn's disease by AIEC bacteria expressing such a virulence factor may be at the origin of early-stage lesions in Peyer's patches.

These findings open the way to a greater understanding of the role of infective factors in triggering this disease. Studies are now under way to identify the receptor involved in the interaction between bacteria and Peyer's patches, which will open new therapeutic opportunities to block this early stage in the infective process.