title: Subversion of autophagy in adherent invasive Escherichia coli-infected neutrophils induces inflammation and cell death.
abstract: Invading bacteria are recognized, captured and killed by a specialized form of autophagy, called xenophagy. Recently, defects in xenophagy in Crohn's disease (CD) have been implicated in the pathogenesis of human chronic inflammatory diseases of uncertain etiology of the gastrointestinal tract. We show here that pathogenic adherent-invasive Escherichia coli (AIEC) isolated from CD patients are able to adhere and invade neutrophils, which represent the first line of defense against bacteria. Of particular interest, AIEC infection of neutrophil-like PLB-985 cells blocked autophagy at the autolysosomal step, which allowed intracellular survival of bacteria and exacerbated interleukin-8 (IL-8) production. Interestingly, this block in autophagy correlated with the induction of autophagic cell death. Likewise, stimulation of autophagy by nutrient starvation or rapamycin treatment reduced intracellular AIEC survival and IL-8 production. Finally, treatment with an inhibitor of autophagy decreased cell death of AIEC-infected neutrophil-like PLB-985 cells. In conclusion, excessive autophagy in AIEC infection triggered cell death of neutrophils.
authors.affiliation: Institute for Research on Cancer and Aging, Nice, France.
authors.forename: Abderrahman
authors.initials: A
authors.lastname: Chargui
authors.forename: Annabelle
authors.initials: A
authors.lastname: Cesaro
authors.forename: Sanda
authors.initials: S
authors.lastname: Mimouna
authors.forename: Mohamed
authors.initials: M
authors.lastname: Fareh
authors.forename: Patrick
authors.initials: P
authors.lastname: Brest
authors.forename: Philippe
authors.initials: P
authors.lastname: Naquet
authors.forename: Arlette
authors.initials: A
authors.lastname: Darfeuille-Michaud
authors.forename: Xavier
authors.initials: X
authors.lastname: Hébuterne
authors.forename: Baharia
authors.initials: B
authors.lastname: Mograbi
authors.forename: Valérie
authors.initials: V
authors.lastname: Vouret-Craviari
authors.forename: Paul
authors.initials: P
authors.lastname: Hofman
mesh_terms: D001343:Autophagy / Q000276:immunology*; D001422:Bacterial Adhesion / Q000276:immunology; D016923:Cell Death / Q000276:immunology; D002460:Cell Line; D004926:Escherichia coli / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000382:microbiology*; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D015398:Signal Transduction