Effect of Helicobacter pylori’s vacuolating cytotoxin on the autophagy pathway in gastric epithelial cells

TEREBIZNIK, M. R.; VAZQUEZ C. L.,; RAJU, D.; TORBRICKI, K.; KULKARNI, R.; BLANKE, S.; YOSHIMORI, T.; COLOMBO, M. I.; JONES, N. L.

Autophagy

Landes Bioscience

Año: 2009 vol. 5 p. 370 - 379

1554-8627

Host cell responses to Helicobacter pylori infection are complexand incompletely understood. Here, we report that autophagyis induced within human-derived gastric epithelial cells (AGS)in response to H. pylori infection. These autophagosomes weredistinct and different from the large vacuoles induced during H.pylori infection. Autophagosomes were detected by transmissionelectron microscopy, conversion of LC3-I to LC3-II, GFP-LC3recruitment to autophagosomes, and depended on Atg5 andAtg12. The induction of autophagy depended on the vacuolatingcytotoxin (VacA) and, moreover, VacA was sufficient to induceautophagosome formation. The channel-forming activity of VacAwas necessary for inducing autophagy. Intracellular VacA partiallyco-localized with GFP-LC3, indicating that the toxin associateswith autophagosomes. The inhibition of autophagy increased thestability of intracellular VacA, which in turn resulted in enhancedtoxin-mediated cellular vacuolation. These findings suggest thatthe induction of autophagy by VacA may represent a host mechanismto limit toxin-induced cellular damage.