Cytotoxin-Associated Gene A-Negative Helicobacter pylori Promotes Gastric Mucosal CX3CR1(+)CD4(+) Effector Memory T Cell Recruitment in Mice.
Cytotoxin-Associated Gene A-Negative Helicobacter pylori Promotes Gastric Mucosal CX3CR1(+)CD4(+) Effector Memory T Cell Recruitment in Mice.
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DOI：
10.3389/fmicb.2022.813774
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发表时间：
2022
影响因子：
5.2
通讯作者：
Wu C
中科院分区：
文献类型：
--
作者：
Sun H;He T;Wu Y;Yuan H;Ning J;Zhang Z;Deng X;Li B;Wu C
幽门螺杆菌可引起多种胃病，从胃炎到胃癌。细胞毒素相关基因A(CagA)+幽门螺杆菌比CagA-H.然而，其潜在的机制还需要进一步研究。给小鼠灌胃等量的CagA+或CagA-H.Pylori。四周后，用小鼠趋化因子阵列检测胃中的24种趋化因子，并分析招募的胃CD4+T细胞的表型。对其迁移途径进行了评价。最后，通过皮尔逊相关分析，确定招募的CD4+T细胞亚群、幽门螺杆菌定植水平和组织病理损伤评分之间的相关性。CagA-Hp感染的胃粘膜中趋化因子CCL3和CX3CL1的浓度显著高于CagA+Hp感染的胃粘膜。其中，CX3CL1由胃上皮细胞分泌，由CagA-H.Pylori比CagA+菌株更有效地诱导，显著促进粘膜CD4+T细胞的迁移。在CagA-Hp感染的胃组织中，CX3CL1受体CX3CR1的表达上调。此外，CX3CR1阳性的胃CD4+T细胞多为CD44+CD69-CCR7效应记忆T细胞(Tem)。Pearson相关分析显示，CX3CR1+CD4+Tem细胞数量与幽门螺杆菌定植水平和组织病理损伤评分呈负相关。CagA-H.Pylori促进小鼠胃粘膜CX3CR1+CD4+Tem募集。
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. 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. 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. CagA–H. pylori promotes gastric mucosal CX3CR1+CD4+ Tem recruitment in mice.