Helicobacter pylori is a Gram-negative bacterium that infects approximately 50% of the global population. H. pylori resides within the stomach in close proximity to gastric epithelial cells, while avoiding direct contact with immune cells. During H. pylori infection, epithelial cells lining the gastric mucosa initiate pro-inflammatory immune responses via the secretion of cytokines and chemokines that function to recruit immune cells to the local tissue. However, the contribution of extracellular vesicles (EVs) released by gastric epithelial cells in promoting pathogenesis in response to H. pylori infection is unclear.
In this study, we aimed to determine the composition and function of EVs secreted by gastric epithelial cells in response to H. pylori infection. To examine this, EVs secreted by gastric epithelial (AGS) cells infected with H. pylori, or non-infected as controls, were isolated and purified using differential ultracentrifugation and density gradients. The quantity and morphology of EVs produced in response to H. pylori infection was determined using TEM and nanoparticle tracking analyses. To further understand how EVs impact cell-to-cell communication, EVs obtained from H. pylori-stimulated AGS cells were added to AGS cells that were subsequently infected with H. pylori. Examination of EV-treated AGS cells revealed decreased production of interleukin-8 in response to H. pylori infection. To further elucidate the underlying mechanism driving this effect, the proteome of EVs secreted from H. pylori-infected and non-infected AGS cells is currently being examined to identify potential candidates of EV-mediated immunoregulation.
Together, these results provide novel insights into the contribution of EVs in mediating cell-to-cell communication and modulating pathogenesis in the host. Further investigation into the role of EVs during H. pylori infection will provide novel insights regarding the mechanisms whereby pathogens modulate inflammation at the mucosal epithelial cell surface and will promote the future development of novel interventions to combat H. pylori infections.