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.
Highlights
Host survival is dependent on effective recognition and killing of pathogens
Intracellular Survival of adherent-invasive Escherichia coli (AIEC) within Neutrophils Since AIEC are able to adhere to and invade epithelial cells and macrophages [7,8], the aim of this study was first to evaluate whether AIEC LF82 invade and survive within neutrophils and second to analyze the consequence of survival of intracellular bacteria on neutrophil life span
Xenophagy-mediated killing of bacteria has so far been demonstrated in macrophages [27,33], fibroblasts [34,35], and epithelial cells [26], but no information is available concerning this process in neutrophils
Summary
Host survival is dependent on effective recognition and killing of pathogens Professional phagocytes such as neutrophils, macrophages and dendritic cells directly kill microorganisms through phagocytosis and via the production of reactive oxygen intermediates, proteolytic enzymes and cytokines. Among these cells, neutrophils are the first line of innate defence recruited at the site of infection. The rapid execution of neutrophil death is central for the resolution of infection These cells have a short life span in the circulation–only 5 days–and rapidly go into apoptosis [1]. This issue is critical as excessive or dysregulated neutrophil responses contribute to persisting tissue damage that underlies many inflammatory diseases
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