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

Abstract

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.AimThis study explores the possibility that GM‐CSF plays a role in the reduction of H. pylori infection following vaccination.ResultsWe 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 βdefensin3, which exhibits H. pylori bactericidal activities.ConclusionTaken together, we demonstrate a key role of GM‐CSF, most probably originating from Th17 cells, in the vaccine‐induced reduction of H. pylori infection.