2012
DOI: 10.1053/j.gastro.2012.01.043
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Vacuolating Cytotoxin and Variants in Atg16L1 That Disrupt Autophagy Promote Helicobacter pylori Infection in Humans

Abstract: Background & Aims The Helicobacter pylori toxin vacuolating cytotoxin (VacA) promotes gastric colonization and its presence (VacA+) is associated with more-severe disease. The exact mechanisms by which VacA contributes to infection are unclear. We previously found that limited exposure to VacA induces autophagy of gastric cells, which eliminates the toxin; we investigated whether autophagy serves as a defense mechanism against H pylori infection. Methods We investigated the effect of VacA on autophagy in hum… Show more

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Cited by 200 publications
(265 citation statements)
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“…It is likely that both factors act on entirely different pathways. VacA has been described to prevent phagosome maturation in macrophages (28) and to prevent autophagy in epithelial cells (29), both of which could also be true in DCs and might explain their failure to respond properly to ΔvacA H. pylori. Interestingly, the tolerizing activity of VacA does not seem to be linked to the vacuolating cytotoxicity attributed to some of its variants.…”
Section: Discussionmentioning
confidence: 99%
“…It is likely that both factors act on entirely different pathways. VacA has been described to prevent phagosome maturation in macrophages (28) and to prevent autophagy in epithelial cells (29), both of which could also be true in DCs and might explain their failure to respond properly to ΔvacA H. pylori. Interestingly, the tolerizing activity of VacA does not seem to be linked to the vacuolating cytotoxicity attributed to some of its variants.…”
Section: Discussionmentioning
confidence: 99%
“…ATG16L1-mediated autophagy impairment has also been investigated in 2 separate cohorts, which demonstrated a significant association between Crohn disease and the increased susceptibility to Helicobacter pylori infection. 98 In another study on T300A Crohn disease patients, a significantly increased presence of AIEC was observed in Paneth cells. 99 Therefore, as a result of this deficiency in bacterial clearance, the ATG16L1 risk variant has been associated with shifts in the microbial compositions of the intestine 100 and, additionally, has been related to the presence of bacterial DNA and an increased formation of antibacterial antibodies in patients with Crohn disease.…”
Section: Atg16l1-dependent Signaling In Crohn Diseasementioning
confidence: 93%
“…Additional recent studies have shown that VacA induces autophagy, but the pathway has not been identified (28,29). Autophagy can promote the survival of dying cells (30).…”
mentioning
confidence: 99%