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

Abstract

Background: Helicobacter 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 methods: Mice 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.

Results: The 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.

Conclusion: CagA^- H. pylori promotes gastric mucosal CX3CR1⁺CD4⁺ Tem recruitment in mice.

Keywords: CX3CL1; CX3CR1; CagA; Helicobacter pylori; effector memory T cell.