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

Author:

Sun Heqiang,He Taojun,Wu Yanan,Yuan Hanmei,Ning Jie,Zhang Zhenhua,Deng Xinli,Li Bin,Wu Chao

Abstract

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 CagAH. pylori. However, the underlying mechanism needs to be further investigated.Materials and methodsMice were intragastrically administered equal amounts of CagA+ or CagAH. 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 CagAH. 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 CagAH. 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 CagAH. pylori-infected stomach. In addition, most of the CX3CR1-positive gastric CD4+ T cells were CD44+CD69CCR7 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.ConclusionCagAH. pylori promotes gastric mucosal CX3CR1+CD4+ Tem recruitment in mice.

Funder

National Natural Science Foundation of China

Publisher

Frontiers Media SA

Subject

Microbiology (medical),Microbiology

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