title: Abnormally expressed ER stress response chaperone Gp96 in CD favours adherent-invasive Escherichia coli invasion.
abstract: OBJECTIVE
  Crohn's disease (CD) ileal lesions are colonised by pathogenic adherent-invasive Escherichia coli (AIEC) producing outer membrane vesicles (OMVs) that contribute to the bacterial invasion process. In addition, increased expression of endoplasmic reticulum (ER)-localised stress response proteins, due to ER stress, is observed in patients with CD. The expression of the ER-localised stress response protein Gp96 in patients with CD and its biological role with regards to the ability of AIEC to invade intestinal epithelial cells were analysed.
  
  
  RESULTS
  Immunohistochemistry on tissue arrays showed that, together with CEACAM6 (carcinoembryonic antigen-related cell adhesion molecule 6) or the ER stress protein Grp78, Gp96 is also strongly expressed at the apical plasma membrane of the ileal epithelial cells of 50% of patients with CD. Invasion experiments in the presence of antibodies raised against Gp96, or after transfection of Intestine-407 cells with gp96 small interfering RNA (siRNA), indicated that Gp96 is essential to promote AIEC LF82 invasion, allowing, via the recognition of the outer membrane protein OmpA, OMVs to fuse with intestinal epithelial cells.
  
  
  CONCLUSIONS
  Gp96 is overexpressed on the apical surface of ileal epithelial cells in patients with CD and acts as a host cell receptor for OMVs, promoting AIEC invasion. From the results shown here, it is speculated that AIEC could take advantage of the abnormal expression of Gp96 in patients with CD to invade the ileal mucosa.
authors.affiliation: Pathogénie Bactérienne Intestinale, Université d'Auvergne, CBRV, 28 place Henri Dunant, Clermont-Ferrand, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rolhion
authors.forename: Nicolas
authors.initials: N
authors.lastname: Barnich
authors.forename: Marie-Agnès
authors.initials: MA
authors.lastname: Bringer
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Glasser
authors.forename: Julien
authors.initials: J
authors.lastname: Ranc
authors.forename: Xavier
authors.initials: X
authors.lastname: Hébuterne
authors.forename: Paul
authors.initials: P
authors.lastname: Hofman
authors.forename: Arlette
authors.initials: A
authors.lastname: Darfeuille-Michaud
mesh_terms: D000328:Adult; D001422:Bacterial Adhesion / Q000502:physiology; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D018938:Caco-2 Cells; D003424:Crohn Disease / Q000378:metabolism* / Q000382:microbiology; D000091342:Endoplasmic Reticulum Chaperone BiP; D004926:Escherichia coli / Q000378:metabolism / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000150:complications* / Q000378:metabolism; D005260:Female; D006801:Humans; D007082:Ileum / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014774:Virulence; D055815:Young Adult
chemical_list: D001425:Bacterial Outer Membrane Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; C053387:endoplasmin; C078167:OMPA outer membrane proteins; D007371:Interferon-gamma