Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Wrighton, S.
The role of the NKG2D receptor during infection with Helicobacter pylori
Humanmedizin; [ Diplomarbeit ] Graz Medical University; 2018. pp.
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Gorkiewicz Gregor
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- Abstract:
- Helicobacter pylori is a bacterium with a capacity to evade the host’s immune system. Some of these immune evasion mechanisms have been identified, but many remain unknown. The NKG2D receptor is an immunoreceptor implicated in the detection stressed, malignant, infected cells via its ligands. There is growing evidence that host microbiota-mediated modulation of the NKG2D receptor, plays a key role in the genesis and progression of many gastrointestinal disorders. A recent study found no difference between the levels of NKG2D expressed by the lymphocyte populations in normal stomach mucosa and in the stomachs of people suffering from H.pylori gastritis. This discovery prompted us to postulate an involvement of soluble NKG2D ligands (MICA and MICB) released by the matrix metalloproteinase ADAM17; a hypothesis that is moreover supported by a previous demonstration of activation of this “sheddase” by the protein CagL, a subunit of H.pylori’s type 4 secretion system. In experiments designed to test the above hypothesis, cultured gastric epithelial cell lines were infected with wild type H.pylori or a knockout mutant. Quantitative polymerase chain reaction was used to assess subsequent gene expression changes. To determine the actual ligand expression of cells we employed flow cytometric assays. Increased gene expression for both MIC ligands and ADAM17 was observed with MKN28 cells 24 hours after infection. Gene expression of interleukin-15 was also increased starting at 4 hours post-infection. Flow cytometric analyses with 3 different gastric cell lines on the other hand produced highly variable and inconclusive results. Whilst AGS cells infected with the wild type strain expressed lower levels of MIC ligands than those infected with the knockout mutant, an opposite response was observed for the other 2 lines. Altogether, the results paint an unclear picture and further investigations will be necessary to unequivocally prove or disprove our hypothesis.