Enhanced E. coli LF82 translocation through follicle-associated epithelium in Crohn’s disease is dependent on long polar fimbriae and CEACAM6-expression, and increases paracellular permeability.
J Crohns Colitis. 2019 Aug 09;:
Authors: Keita ÅV, Alkaissi LY, Holm EB, Heil SDS, Chassaing B, Darfeuille-Michaud A, McKay DM, Söderholm JD
BACKGROUND & AIMS: Patients with Crohn’s disease (CD) harbour an increased number of adherent-invasive E. coli (AIEC). The strain LF82, identified in the ileal mucosa of CD patients, has been extensively studied for pathogenic mechanisms. However, understanding of the interaction of LF82 with the intestinal mucosa of CD patients is lacking.
METHODS: Here, we investigated the importance of long polar fimbriae (LPF) type 1 pili and the carcinoembryonic antigen-related cell-adhesion molecule 6 (CEACAM6) for translocation of LF82 in an in vitro model of follicle-associated epithelium (FAE) and in FAE and villus epithelium (VE) of CD patients and controls using Ussing chambers.
RESULTS: Significantly greater LF82-passage occurred in the FAE model compared to VE Caco-2cl1 monoculture. Moreover, bacterial translocation was inhibited by either LPF disruption or pre-incubation with anti-CEACAM6 antibody. Tissue mounted on Ussing chambers showed significantly higher LF82-passage in CD FAE compared to control FAE, that was diminished in LF82 lacking LPF and by blocking host CEACAM6. Interestingly, addition of LF82 to the CD FAE tissues significantly increased paracellular permeability (51Chromium-EDTA) compared to baseline, and the increase was inhibited by anti-CEACAM6. Immunofluorescence and immunoblots showed higher expression of CEACAM6 in FAE of CD compared to controls.
CONCLUSIONS: These data suggest that FAE of CD patients is a site of vulnerability for invasion by LF82, in a way that require both bacterial-LPF and host-CEACAM6. Further, LF82 has the ability to increase paracellular passage through FAE of CD. These data can help define novel therapeutic targets in CD to prevent clinical recurrence.
PMID: 31393983 [PubMed – as supplied by publisher]