Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Montalban Arques, A.
The NKG2D system as modulator of host-microbial interactions in the gut
PhD-Studium (Doctor of Philosophy); Humanmedizin; [ Dissertation ] Graz Medical University; 2016. pp.
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- Autor*innen der Med Uni Graz:
- Montalban-Arques Ana Maria
- Betreuer*innen:
- Gorkiewicz Gregor
- Krause Robert
- Altmetrics:
- Abstract:
- The human gastrointestinal tract (GIT) represents the largest reservoir of commensal bacteria as well as the largest immune system of the body. Moreover, microbes are crucial for the development of the immune system. However, alterations in either the microbiota or the immune system may lead to gastrointestinal (GI) disorders. The natural killer group 2 member D (NKG2D) system is critical in the recognition of cell stress due to cell transformation or infection. Recently, it has been demonstrated that gut microbiota can modulate the expression of NKG2D ligands. Interestingly, the activation of the NKG2D has been associated with GI diseases, such as celiac disease (CeD) or inflammatory bowel disease, wherein the microbiota is also impaired. In this study, we have identified Propionibacterium acnes being associated with lymphocytic gastritis, a chronic form of gastritis often associated to CeD. Moreover, we have seen that patients suffering from LyG show an activation of the NKG2D system, which does not happen in the gastritis triggered by Helicobacter pylori. Using gastric epithelial cell (EC) lines, we demonstrated that P. acnes and the microbial products short-chain fatty acids, can induce the expression of NKG2D ligands in vitro. However, H. pylori omitted or even repressed their expression. Interestingly, in lymphocytic colitis, a pathology presenting similar features with LyG, the NKG2D system is not activated, maybe due to differences in the microbiota composition and immune cells found in both organs. Moreover, Caco-2 colon ECs also showed a different NKG2D system response when challenged with SCFAs compared to gastric ECs, suggesting this system plays a role in the gut that is location-dependent. Finally, using a mouse model lacking the NKG2D receptor, we saw that the NKG2D system activity is linked to TLRs expression along the GIT, that is location and genotype-dependent. Interestingly, we found subtle differences in the microbiota that were NKG2D-dependent. Thus, we could demonstrate that NKG2D system is important in the modulation of the gut microbiota and this system could be a target in the treatment of GI disorders.