Effect of Helicobacter pylori's vacuolating cytotoxin on the autophagy pathway in gastric epithelial cells.
Host cell responses to Helicobacter pylori infection are complex and incompletely understood. Here, we report that autophagy is induced within human-derived gastric epithelial cells (AGS) in response to H. pylori infection. These autophagosomes were distinct and different from the large vacuoles induced during H. pylori infection. Autophagosomes were detected by transmission electron microscopy, conversion of LC3-I to LC3-II, GFP-LC3 recruitment to autophagosomes, and depended on Atg5 and Atg12. The induction of autophagy depended on the vacuolating cytotoxin (VacA) and, moreover, VacA was sufficient to induce autophagosome formation. The channel-forming activity of VacA was necessary for inducing autophagy. Intracellular VacA partially co-localized with GFP-LC3, indicating that the toxin associates with autophagosomes. The inhibition of autophagy increased the stability of intracellular VacA, which in turn resulted in enhanced toxin-mediated cellular vacuolation. These findings suggest that the induction of autophagy by VacA may represent a host mechanism to limit toxin-induced cellular damage.
Terebiznik
Mauricio R
MR
Cell Biology Program, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada.
Raju
Deepa
D
Vázquez
Cristina L
CL
Torbricki
Karl
K
Kulkarni
Reshma
R
Blanke
Steven R
SR
Yoshimori
Tamotsu
T
Colombo
María I
MI
Jones
Nicola L
NL
D000818:Animals; D001343:Autophagy; D000071192:Autophagy-Related Protein 12; D000071187:Autophagy-Related Protein 5; D001426:Bacterial Proteins / Q000378:metabolism / Q000502:physiology*; D003470:Culture Media / Q000378:metabolism; D003603:Cytotoxins / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism* / Q000382:microbiology*; D005347:Fibroblasts / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism*; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D051379:Mice; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism; D013270:Stomach / Q000382:microbiology*
C466624:ATG12 protein, human; C502778:ATG5 protein, human; D000071192:Autophagy-Related Protein 12; D000071187:Autophagy-Related Protein 5; D001426:Bacterial Proteins; D003470:Culture Media; D003603:Cytotoxins; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; C074689:VacA protein, Helicobacter pylori