title: Adherent-invasive Escherichia coli isolated from Crohn's disease patients induce granulomas in vitro.
abstract: Adherent-invasive Escherichia coli (AIEC) have been shown to be highly associated with ileal Crohn's disease (CD). AIEC survive within infected macrophages, residing within the phagolysosomal compartment where they take advantage of the low pH to replicate extensively. We investigated whether, like the tuberculous bacillus which also persists within macrophages, AIEC LF82 induces the formation of granulomas, which are a common histopathological feature of CD. For this purpose, we have taken advantage of an in vitro model of human granulomas that we recently developed, based on blood-derived mononuclear cells. We demonstrated that AIEC LF82 induces aggregation of infected macrophages, fusion of some of them to form multinucleated giant cells and subsequent recruitment of lymphocytes. Light microscopy and scanning electron microscopy analysis of the cell aggregates confirmed their granuloma features. This was further confirmed by histological analysis of granuloma sections. Noteworthy, this phenomenon can be reproduced by soluble protein extracts of AIEC LF82 coated onto beads. Although the cell aggregates not completely mimic natural CD-associated granulomas, they are very similar to early stages of epithelioid granulomas.
authors.affiliation: Department Molecular Mechanisms of Mycobacterial Infections, IPBS, CNRS UMR5089, Toulouse 31077, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Meconi
authors.forename: Alain
authors.initials: A
authors.lastname: Vercellone
authors.forename: Florence
authors.initials: F
authors.lastname: Levillain
authors.forename: Bruno
authors.initials: B
authors.lastname: Payré
authors.forename: Talal
authors.initials: T
authors.lastname: Al Saati
authors.forename: Florence
authors.initials: F
authors.lastname: Capilla
authors.forename: Pierre
authors.initials: P
authors.lastname: Desreumaux
authors.forename: Arlette
authors.initials: A
authors.lastname: Darfeuille-Michaud
authors.forename: Frédéric
authors.initials: F
authors.lastname: Altare
mesh_terms: D001422:Bacterial Adhesion; D002449:Cell Aggregation; D002478:Cells, Cultured; D003424:Crohn Disease / Q000382:microbiology*; D004926:Escherichia coli / Q000254:growth & development* / Q000648:ultrastructure; D004927:Escherichia coli Infections / Q000382:microbiology*; D006099:Granuloma / Q000382:microbiology*; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000382:microbiology; D008855:Microscopy, Electron, Scanning; D009000:Monocytes / Q000166:cytology / Q000382:microbiology / Q000648:ultrastructure; D010588:Phagosomes / Q000382:microbiology