1. Enhanced E. coli LF82 Translocation through the Follicle-associated Epithelium in Crohn’s Disease is Dependent on Long Polar Fimbriae and CEACAM6 expression, and Increases Paracellular Permeability
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Derek M. McKay, Arlette Darfeuille-Michaud, Johan D. Söderholm, Elin B Holm, Lina Yakymenko Alkaissi, Åsa V. Keita, Stéphanie D S Heil, Benoit Chassaing, Georgia State University, University System of Georgia (USG), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and International Organization for the Study of Inflammatory Bowel Disease Lions Clubs International Foundation Swedish Research Council [VR-Medicine and Health] 2014-025372017-02475ALF Grants Region Ostergotland
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Adult ,Male ,Cell Membrane Permeability ,Adolescent ,Fimbria ,Ileum ,Chromosomal translocation ,Gastroenterology and Hepatology ,Immunofluorescence ,GPI-Linked Proteins ,Inflammatory bowel disease ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Intestinal mucosa ,Crohn Disease ,Antigens, CD ,Gastroenterologi ,medicine ,Escherichia coli ,Humans ,Intestinal Mucosa ,mucosal barrier ,030304 developmental biology ,Aged ,Aged, 80 and over ,0303 health sciences ,medicine.diagnostic_test ,business.industry ,Gastroenterology ,Mucous membrane ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,General Medicine ,Original Articles ,Middle Aged ,Molecular biology ,Epithelium ,3. Good health ,permeability ,medicine.anatomical_structure ,Paracellular transport ,Bacterial Translocation ,Fimbriae, Bacterial ,030211 gastroenterology & hepatology ,Female ,Caco-2 Cells ,business ,Cell Adhesion Molecules - Abstract
Background and 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 the FAE and villus epithelium [VE] of patients with CD and controls, using Ussing chambers. Results Significantly greater LF82 passage occurred in the FAE model compared with in the VE Caco-2cl1 mono-culture. Moreover, bacterial translocation was inhibited by either LPF disruption or pre-incubation with anti-CEACAM6 antibody. Tissue mounted in Ussing chambers showed significantly higher LF82 passage in FAE from patients with CD compared with 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 [of 51Chromium-EDTA] compared with baseline, and the increase was inhibited by anti-CEACAM6. Immunofluorescence and immunoblots showed higher expression of CEACAM6 in FAE of patients with CD compared with in FAE from controls. Conclusions These data suggest that the FAE of CD patients is a site of vulnerability for invasion by LF82 via a mechanism that requires both bacterial LPF and host CEACAM6. Further, LF82 has the ability to increase paracellular passage through the FAE of patients with CD. These data can help define novel therapeutic targets in CD for the prevention of clinical recurrence.
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