Cytotoxin-Associated Gene A-Negative Helicobacter pylori Promotes Gastric Mucosal CX3CR1+CD4+ Effector Memory T Cell Recruitment in Mice

BackgroundHelicobacter pylori can cause many kinds of gastric disorders, ranging from gastritis to gastric cancer. Cytotoxin-associated gene A (CagA)H+. pylori is more likely to cause gastric histopathologic damage than CagA(-)H. pylori. However, the underlying mechanism needs to be further investigated.Materials and methodsMice were intragastrically administered equal amounts of CagA(+) or CagA(-)H. pylori. Four weeks later, 24 chemokines in stomachs were measured using a mouse chemokine array, and the phenotypes of the recruited gastric CD4(+) T cells were analyzed. The migration pathway was evaluated. Finally, the correlation between each pair among the recruited CD4(+) T cell sub-population, H. pylori colonization level, and histopathologic damage score were determined by Pearson correlation analysis.ResultsThe concentration of chemokines, CCL3 and CX3CL1, were significantly elevated in CagA(-)H. pylori-infected gastric mucosa than in CagA(+)H. pylori-infected gastric mucosa. Among them, CX3CL1 secreted by gastric epithelial cells, which was elicited more effectively by CagA(-)H. pylori than by the CagA(+) strain, dramatically promoted mucosal CD4(+) T cell migration. The expression of CX3CR1, the only known receptor of CX3CL1, was upregulated on the surface of gastric CD4(+) T cells in CagA(-)H. pylori-infected stomach. In addition, most of the CX3CR1-positive gastric CD4(+) T cells were CD44(+)CD69(-)CCR7(-) effector memory T cells (Tem). Pearson correlation analysis showed that the recruited CX3CR1(+)CD4(+) Tem cell population was negatively correlated with H. pylori colonization level and histopathologic damage score.ConclusionCagA(-)H. pylori promotes gastric mucosal CX3CR1(+)CD4(+) Tem recruitment in mice.

Automated summary

The study found that CagA(-)H. pylori infection resulted in significantly elevated levels of chemokines CCL3 and CX3CL1 in the gastric mucosa. These chemokines promoted the migration of CD4(+) T cells, with the upregulation of the CX3CR1 receptor mainly in the CD4(+) effector memory T cell subset.