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Helicobacter pylori urease binds to class II MHC on gastric epithelial cells and induces their apoptosis
1Departments of Pediatrics, Internal Medicine, and Microbiology and Immunology, and the Sealy Center for Molecular Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA.
Abstract:
Infection by Helicobacter pylori leads to injury of the gastric epithelium and a cellular infiltrate that includes CD4+ T cells. H. pylori binds to class II MHC molecules on gastric epithelial cells and induces their apoptosis. Because urease is an abundant protein expressed by H. pylori, we examined whether it had the ability to bind class II MHC and induce apoptosis in class II MHC-bearing cells. Flow cytometry revealed the binding of PE-conjugated urease to class II MHC+ gastric epithelial cell lines. The binding of urease to human gastric epithelial cells was reduced by anti-class II MHC Abs and by staphylococcal enterotoxin B. The binding of urease to class II MHC was confirmed when urease bound to HLA-DR1-transfected COS-1 (1D12) cells but not to untransfected COS-1 cells. Urease also bound to a panel of B cell lines expressing various class II MHC alleles. Recombinant urease induced apoptosis in gastric epithelial cells that express class II MHC molecules, but not in class II MHC- cells. Also, Fab from anti-class II MHC and not from isotype control Abs blocked the induction of apoptosis by urease in a concentration-dependent manner. The adhesin properties of urease might point to a novel and important role of H. pylori urease in the pathogenesis of H. pylori infection.
Insights
Helicobacter pylori urease binds to gastric epithelial cells expressing MHC class II molecules, inducing apoptosis. This suggests urease plays a key role in H. pylori pathogenesis.
Area of Science:
- Immunology
- Microbiology
- Gastroenterology
Background:
- Helicobacter pylori infection causes gastric injury and immune cell infiltration.
- H. pylori interacts with gastric epithelial cells, inducing apoptosis via Class II MHC molecules.
- Urease is a highly abundant H. pylori protein.
Purpose of the Study:
- To investigate if H. pylori urease binds to Class II MHC molecules.
- To determine if urease induces apoptosis in Class II MHC-bearing cells.
- To explore the role of urease in H. pylori pathogenesis.
Main Methods:
- Flow cytometry to detect urease binding to gastric epithelial cells.
- Use of anti-Class II MHC antibodies and staphylococcal enterotoxin B to block binding.
- Testing urease-induced apoptosis in Class II MHC+ and Class II MHC- cells.
- Confirmation of binding using HLA-DR1-transfected COS-1 cells.
Main Results:
- PE-conjugated urease bound to Class II MHC+ gastric epithelial cell lines.
- Urease binding was inhibited by anti-Class II MHC antibodies and staphylococcal enterotoxin B.
- Recombinant urease induced apoptosis in Class II MHC+ cells, but not in Class II MHC- cells.
- Anti-Class II MHC antibodies blocked urease-induced apoptosis.
Conclusions:
- H. pylori urease binds to Class II MHC molecules on gastric epithelial cells.
- Urease induces apoptosis in a Class II MHC-dependent manner.
- Urease's adhesin properties suggest a significant role in H. pylori infection pathogenesis.