Defects in autophagy favour adherent-invasive Escherichia coli persistence within macrophages leading to increased pro-inflammatory response
Article first published online: 1 MAR 2012
© 2012 Blackwell Publishing Ltd
Volume 14, Issue 6, pages 791–807, June 2012
How to Cite
Lapaquette, P., Bringer, M.-A. and Darfeuille-Michaud, A. (2012), Defects in autophagy favour adherent-invasive Escherichia coli persistence within macrophages leading to increased pro-inflammatory response. Cellular Microbiology, 14: 791–807. doi: 10.1111/j.1462-5822.2012.01768.x
- Issue published online: 16 MAY 2012
- Article first published online: 1 MAR 2012
- Accepted manuscript online: 6 FEB 2012 10:20PM EST
- Received 1 July, 2011; revised 23 January, 2012; accepted 30 January, 2012.
Ileal lesions in Crohn's disease (CD) patients are abnormally colonized by pathogenic adherent-invasive Escherichia coli (AIEC). AIEC bacteria are able to replicate within epithelial cells after lysis of the endocytic vacuole and within macrophages in a large vacuole. CD-associated polymorphisms in NOD2, ATG16L1 and IRGM affect bacterial autophagy, a crucial innate immunity mechanism. We previously determined that defects in autophagy impaired the ability of epithelial cells to control AIEC replication. AIEC behave differently within epithelial cells and macrophages and so we investigated the impact of defects in autophagy on AIEC intramacrophagic replication and pro-inflammatory cytokine response. AIEC bacteria induced the recruitment of the autophagy machinery at the site of phagocytosis, and functional autophagy limited AIEC intramacrophagic replication. Impaired ATG16L1, IRGM or NOD2 expression induced increased intramacrophagic AIEC and increased secretion of IL-6 and TNF-α in response to AIEC infection. In contrast, forced induction of autophagy decreased the numbers of intramacrophagic AIEC and pro-inflammatory cytokine release, even in a NOD2-deficient context. On the basis of our findings, we speculate that stimulating autophagy in CD patients would be a powerful therapeutic strategy to concomitantly restrain intracellular AIEC replication and slow down the inflammatory response.