Subversion of autophagy in adherent invasive Escherichia coli-infected neutrophils induces inflammation and cell death

PLoS One. 2012;7(12):e51727. doi: 10.1371/journal.pone.0051727. Epub 2012 Dec 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy / immunology*
  • Bacterial Adhesion / immunology
  • Cell Death / immunology
  • Cell Line
  • Escherichia coli / immunology*
  • Escherichia coli / metabolism
  • Humans
  • Inflammation / immunology*
  • Inflammation / microbiology*
  • Neutrophils / immunology*
  • Neutrophils / microbiology*
  • Neutrophils / pathology
  • Signal Transduction

Grant support

Funding provided by Infectiopôle Sud PACA (A. Chargui: postdoctoral fellowship), Association François Aupetit, “Institut National de la Santé et de la Recherche Médicale”, “Agence de l’Environnement et de la Maîtrise de l’Energie” (A B and A. Cesaro: convention ADEME n° 08 62 C 0044), “Agence régionale santé Provence Alpes Côte d’Azur and Direction régionale de l’Environnement, de l’aménagement et du logement” (A B: plan régional santé environnement PRSE PACA n°6.3.3.3). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.