Decreased IL-17RB expression impairs CD11b(+)CD11c(-) myeloid cell accumulation in gastric mucosa and host defense during the early-phase of Helicobacter pylori infection Academic Article uri icon

abstract

  • Interleukin-17 receptor B (IL-17RB), a member of the IL-17 receptor family activated by IL-17B/IL-17E, has been shown to be involved in inflammatory diseases. However, the regulation and function of IL-17RB in Helicobacter pylori (H. pylori) infection, especially in the early-phase is still unknown. Here, we found that gastric IL-17RB mRNA and protein were decreased in gastric mucosa of both patients and mice infected with H. pylori. In vitro experiments show that IL-17RB expression was down regulated via PI3K/AKT pathway on gastric epithelial cells (GECs) stimulated with H. pylori in a cagA-involved manner, while in vivo studies showed that the effect was partially dependent on cagA expression. IL-17E was also decreased during the early-phase of H. pylori infection, and provision of exogenous IL-17E resulted in increased CD11b+CD11c- myeloid cells accumulation and decreased bacteria colonization within the gastric mucosa. In the early-phase of H. pylori infection, IL-17E-IL-17RB promoted gastric epithelial cell-derived CXCL1/2/5/6 to attract CD11b+CD11c- myeloid cells, and also contributed to host defense by promoting the production of antibacterial protein Reg3a. This study defines a negative regulatory network involving IL-17E, GECs, IL-17RB, CD11b+CD11c- myeloid cells, and Reg3a in the early-phase of H. pylori infection, which results in an impaired host defense within the gastric microenvironment, suggesting IL-17RB as a potential early intervening target in H. pylori infection.

authors

  • Teng, Yong-sheng
  • Liu, Yu-gang
  • Chen, Xian-hua
  • Wang, Ting-ting
  • Cheng, Ping
  • Lv, Yi-pin
  • Kong, Hui
  • Mao, Fang-yuan
  • Hao, Chuan-jie
  • Yang, Shi-ming
  • Chen, Weisan
  • Zhang, Jin-yu
  • Peng, Liu-sheng
  • Han, Bin
  • Ma, Qiang
  • Han, Jia
  • Zou, Quan-ming
  • Zhuang, Yuan

publication date

  • 2019