GM-CSF is key in the efficacy of vaccine-induced reduction of Helicobacter pylori infection

Background: Helicobacter pylori (H. pylori) colonizes the human gastric mucosa with a high worldwide prevalence. Currently, H. pylori is eradicated by the use of antibiotics. However, elevated antibiotic resistance suggests new therapeutic strategies need to be envisioned: one approach being prophylactic vaccination. Pre-clinical and clinical data show that a urease-based vaccine is efficient in decreasing H. pylori infection through the mobilization of T helper (Th) cells, especially Th17 cells. Th17 cells produce interleukins such as IL-22 and IL-17, among others, and are key players in vaccine efficacy. Recently, granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing Th17 cells have been identified. Aim: This study explores the possibility that GM-CSF plays a role in the reduction of H. pylori infection following vaccination. Results: We demonstrate that GM-CSF+ IL-17(+) Th17 cells accumulate in the stomach mucosa of H. pylori infected mice during the vaccine-induced reduction of H. pylori infection. Secondly, we provide evidence that vaccinated GM-CSF deficient mice only modestly reduce H. pylori infection. Conversely, we observe that an increase in GM-CSF availability reduces H. pylori burden in chronically infected mice. Thirdly, we show that GM-CSF, by acting on gastric epithelial cells, promotes the production of beta defensin3, which exhibits H. pylori bactericidal activities. Conclusion: Taken together, we demonstrate a key role of GM-CSF, most probably originating from Th17 cells, in the vaccine-induced reduction of H. pylori infection.

Automated summary

This study demonstrates the crucial role of GM-CSF, most likely originating from Th17 cells, in the vaccine-induced reduction of H. pylori infection. GM-CSF promotes the production of beta defensin3 by gastric epithelial cells, which exhibits bactericidal activities against H. pylori.