Abstract
Ileal lesions in Crohn's disease (CD) patients are colonized by pathogenic adherent-invasive Escherichia coli (AIEC) able to adhere to and invade intestinal epithelial cells (IEC), and to survive within macrophages. The interaction of AIEC with IEC depends on bacterial factors mainly type 1 pili, flagella, and outer membrane proteins. In humans, proteases can act as host defence mechanisms to counteract bacterial colonization. The protease meprin, composed of multimeric complexes of the two subunits alpha and beta, is abundantly expressed in IECs. Decreased levels of this protease correlate with the severity of the inflammation in patients with inflammatory bowel disease. The aim of the present study was to analyze the ability of meprin to modulate the interaction of AIEC with IECs. In patients with ileal CD we observed decreased levels of meprins, in particular that of meprin β. Dose-dependent inhibition of the abilities of AIEC strain LF82 to adhere to and invade intestinal epithelial T84 cells was observed when bacteria were pre-treated with both exogenous meprin α and meprin β. Dose-dependent proteolytic degradation of type 1 pili was observed in the presence of active meprins, but not with heat-inactivated meprins, and pretreatment of AIEC bacteria with meprins impaired their ability to bind mannosylated host receptors and led to decreased secretion of the pro-inflammatory cytokine IL-8 by infected T84 cells. Thus, decreased levels of protective meprins as observed in CD patients may contribute to increased AIEC colonization.
Highlights
Crohn’s disease (CD) and ulcerative colitis (UC) are the two major forms of idiopathic inflammatory bowel disease (IBD), with a combined prevalence of about 150–200 cases per 100,000 in Western countries
In contrast the level of meprin b mRNA expression was significantly reduced in ileal biopsies of CD patients, compared to that of healthy controls (Fig. 1B, P = 0.0067 Mann-Whitney U test)
We further investigated which bacterial components involved in the abilites of adherent-invasive Escherichia coli (AIEC) bacteria to adhere to and invade intestinal epithelial cells were affected by meprin treatment
Summary
Crohn’s disease (CD) and ulcerative colitis (UC) are the two major forms of idiopathic inflammatory bowel disease (IBD), with a combined prevalence of about 150–200 cases per 100,000 in Western countries. They are multifactorial diseases, occurring in individuals with genetic predisposition in whom an environmental or infectious trigger causes an abnormal immune response [1,2]. Intestinal bacteria are essential for the development of intestinal inflammation. In patients with CD, post-surgical exposure to luminal contents of the terminal ileum is associated with increased inflammation, and diversion of the faecal stream is associated with improvement [4]. The presence of intramucosal Escherichia coli or mucosa-associated E
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