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

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 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.

A role for BCL6 in maintaining CX3CR1+CD4+T cells during helminth infection

“…While CX3CR1 can be involved in immune cell trafficking, this function of CX3CR1 on CD4 T cells is likely to be context specific. For example, one study found in a model of LCMV13 infection CX3CR1 to be dispensable for T cell trafficking to the spleen, lung, and liver, while others have found it necessary in models of Helicobacter pylori infection and allergic asthma (26,28,39). Our own analysis on two different models of helminth infection affecting two different tissues supports this view that CX3CR1 is involved in CD4 + T cell trafficking in some instances but not others.…”

Identification of a novel MSI-related ceRNA network for predicting the prognosis and immunotherapy response of gastric cancer

“…Previously, Heqiang et al found that CagA- Helicobacter pylori infection induced the release of CX3CL1 from the gastric epithelium which subsequently recruited CD4 T memory cells. This recruitment reduced the infection and damage caused by H. pylori [ 33 ]. The CXCL14, which is named as B cell and monocyte-activated chemokine (BMAC) was associated with the deterioration and metastasis of multiple malignant tumors [ 34 ].…”

Single-cell analysis of CX3CR1+cells reveal a pathogenic role for BIRC5+myeloid proliferating cells driven byStaphylococcus aureusleukotoxins

“…These data suggest that a population of BIRC5 + stem-cell-like proliferating cluster of myeloid cells is present in the liver during chronic infection with S. mansoni and could be a general feature of inflammation, not unique to atherosclerosis (3). However, there are also BIRC5 + lymphocytes, which may be derived from a small subset of T cells that can also express CX3CR1 (22,23).…”