Relationship between Helicobacter pylori Infection and Plasmacytoid and Myeloid Dendritic Cells in Peripheral Blood and Gastric Mucosa of Children

Abstract

Purpose To investigate the frequency and activation status of peripheral plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) as well as gastric mucosa DC subset distribution in Helicobacter pylori- (H. pylori-) infected and noninfected children. Materials and Methods Thirty-six children were studied; twenty-one had H. pylori. The frequencies of circulating pDCs (lineage−HLA-DR+CD123+) and mDCs (lineage−HLA-DR+CD11c+) and their activation status (CD83, CD86, and HLA-DR expression) were assessed by flow cytometry. Additionally, the densities of CD11c+, CD123+, CD83+, CD86+, and LAMP3+ cells in the gastric mucosa were determined by immunohistochemistry. Results The frequency of circulating CD83+ mDCs was higher in H. pylori-infected children than in the noninfected controls. The pDCs demonstrated upregulated HLA-DR surface expression, but no change in CD86 expression. Additionally, the densities of gastric lamina propria CD11c+ cells and epithelial pDCs were increased. There was a significant association between frequency of circulating CD83+ mDCs and gastric lamina propria mDC infiltration. Conclusion This study shows that although H. pylori-infected children had an increased population of mature mDCs bearing CD83 in the peripheral blood, they lack mature CD83+ mDCs in the gastric mucosa, which may promote tolerance to local antigens rather than immunity. In addition, this may reduce excessive inflammatory activity as reported for children compared to adults.

The Most Recent Insights into the Roots of Gastric Cancer

“…Although limited studies have been performed ton this topic to date, several authors emphasized the role of H. pylori in modifying the host's immune responses to this infection. Thus, Helmin-Basa recently underlined the lack of mature CD83+ in the gastric tissue samples of children with H. pylori infection, hypothesizing that this peculiarity might enable tolerance to local antigens, decreasing the inflammatory responses [121]. Previous studies of our team supported the implications of innate immunity in promoting or suppressing H. pylori infection in children, revealing the contribution of certain TLR polymorphisms like TLR2 rs3804099 and TLR9 rs352140, as well as of inflammasomes (NLRP3 rs10754558), in augmenting inflammation as a response to this infection [2] (Table 2).…”

The Multifaceted Functionality of Plasmacytoid Dendritic Cells in Gastrointestinal Cancers: A Potential Therapeutic Target?

“…Interestingly, pDCs from H. pylori-infected patients already showed alterations. Patients infected with H. pylori exhibited elevated HLADR expression on circulating pDCs compared to those without H. pylori infection [ 89 ]. Additionally, a higher density of pDCs was observed in the gastric mucosa [ 89 ].…”

“…Patients infected with H. pylori exhibited elevated HLADR expression on circulating pDCs compared to those without H. pylori infection [ 89 ]. Additionally, a higher density of pDCs was observed in the gastric mucosa [ 89 ]. Moreover, it was demonstrated that within the tumor microenvironment of GC, there is a positive correlation between H. pylori infection and the expression of TLR9 and ICOS-L on pDCs [ 90 ].…”

Roles of Plasmacytoid Dendritic Cells in Gastric Cancer

“…As it is well known, H. pylori infection is associated with GC initiation, which leads to active inflammation and immune responses including the changes of pDCs. One study compared pDCs in H. pylori -infected children and noninfected controls and demonstrated upregulated expression of HLA-DR on circulating pDCs, and increased density of pDCs in gastric epithelium mucosa in H. pylori -infected children ( 89 ). Gastric mucosal microbiota analysis from 64 GC patients showed that the diversity, composition, and function of gastric mucosal microbiota was significantly different in tumor tissues compared with normal and peritumoral tissues, and BDCA2 + pDCs and Foxp3 + Tregs were positively correlated from different microhabitats ( 70 ).…”