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

Autor: Laurie Vaillant, Paul Oster, Brynn McMillan, Eulalia Orozco Fernandez, Dominique Velin
Rok vydání: 2022
Předmět:
Zdroj: Helicobacter, vol. 27, no. 2, pp. e12875
ISSN: 1523-5378
1083-4389
DOI: 10.1111/hel.12875
Popis: 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. This study explores the possibility that GM-CSF plays a role in the reduction of H. pylori infection following vaccination. 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 βdefensin3, which exhibits H. pylori bactericidal activities. 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.
Databáze: OpenAIRE