The Effect of Class II Major Histocompatibility Complex Expression on Adherence of Helicobacter pylori and Induction of Apoptosis in Gastric Epithelial Cells: A Mechanism for T Helper Cell Type 1–mediated Damage

Abstract

Helicobacter pylori infection is associated with gastric epithelial damage, including apoptosis, ulceration, and cancer. Although bacterial factors and the host response are believed to contribute to gastric disease, no receptor has been identified that explains how the bacteria attach and signal the host cell to undergo apoptosis. Using H. pylori as “bait” to capture receptor proteins in solubilized membranes of gastric epithelial cells, class II major histocompatibility complex (MHC) molecules were identified as a possible receptor. Signaling through class II MHC molecules leading to the induction of apoptosis was confirmed using cross-linking IgM antibodies to surface class II MHC molecules. Moreover, binding of H. pylori and the induction of apoptosis were inhibited by antibodies recognizing class II MHC. Since type 1 T helper cells are present during infection and produce interferon (IFN)-γ, which increases class II MHC expression, gastric epithelial cell lines were exposed to H. pylori in the presence or absence of IFN-γ. IFN-γ increased the attachment of the bacteria as well as the induction of apoptosis in gastric epithelial cells. In contrast to MHC II–negative cell lines, H. pylori induced apoptosis in cells expressing class II MHC molecules constitutively or after gene transfection. These data describe a novel receptor for H. pylori and provide a mechanism by which bacteria and the host response interact in the pathogenesis of gastric epithelial cell damage.

Gene expression profiling in human gastric mucosa infected with Helicobacter pylori

“…IFNg, one of the major cytokines produced by T cells recruited to the gastric mucosa during infectious and noninfectious gastritis, can increase both class II MHC expression and attachment of the bacteria to gastric epithelial cells, as well as the induction of apoptosis in gastric epithelial cells. 42 Increased IFNg expression reported in the present study is supported by an upregulation of molecules such as the IFITM1. Indeed, IFNg upregulation may be related to an increased risk of developing cancers, as suggested by the upregulation of two other genes FAT10 and IRF-4.…”

Association Between HLA-DQ Genotypes and Haplotypes vs Helicobacter pylori Infection in an Indonesian Population

“…HLA polymorphism is responsible for variation in the immune response of different individuals to various antigens, and contributes to the susceptibility or resistance to infections and autoimmune diseases (Amar et al, 1984;Payami et al, 1986;Todd et al, 1987;1988;Hill et al, 1991). Previous studies have shown that adhesion of H. pylori to gastric epithelial cells transferred with HLA genes leads to different degrees of apoptosis (Fan et al, 1998). The HLA-D region accounts for over 50% of the heritability in hosts (Azuma et al, 1995), and it was also reported that there is an association of HLA-DQA1 and DQB1 genotypes with gastric disease (Rotter et al 1984;Etoglu et al, 1992;Ohmori et al, 1997).…”

Helicobacter pylori persistence: biology and disease

“…When cocultured with epithelial cell lines, H. pylori are antiproliferative and proapoptotic (115, S111), although cag signaling is essentially pro-proliferative (through MAPK signaling and expression of the transcription factor AP-1) (116,117) and pro-and antiapoptotic (through NF-κB signaling) (70,118). Animal models and human studies suggest that the net effect of H. pylori colonization is pro-proliferative and proapoptotic (95,96,119,120, S87, S88). Pro-proliferative signaling increases cell replication and the chance of mutation, whereas apoptosis may be protective by inducing death of DNA-damaged cells.…”