Dokument: Functions of the Aryl hydrocarbon Receptor (AhR) and the AhR-Repressor (AhRR) in defense against Salmonella Typhimurium and Toxoplasma gondii infections
| Titel: | Functions of the Aryl hydrocarbon Receptor (AhR) and the AhR-Repressor (AhRR) in defense against Salmonella Typhimurium and Toxoplasma gondii infections | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=56672 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20210708-104642-9 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Cengiz, Sevgi Can [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. Förster, Irmgard [Gutachter] Prof. Dr. Hegemann, Johannes [Gutachter] | |||||||
| Stichwörter: | Biology, AhR, AhRR, Immunology, Infection, Salmonella Typhimurium, Toxoplasma gondii | |||||||
| Dewey Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik » 570 Biowissenschaften; Biologie | |||||||
| Beschreibung: | The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor, which is required for regulating immune responses and hence needs a strict regulatory mechanism. The AhRrepressor (AhRR) is encoded by target gene of the AhR and regulates AhR activity by negative feedback inhibition. Our group has generated AhRR/eGFP-reporter mice and showed that the AhRR is highly expressed in gut immune cells. In order to study immunoregulatory functions of the AhRR, disease models inducing gut inflammation was used.
Previously, it was shown that AhRR-deficient mice were highly susceptible to dextran sodium sulfate (DSS)-induced colitis, which was accompanied by enhanced Th17/Tc17 and reduced Th1/Tc1 frequencies in the gut. In line, AhRR-deficient mice were susceptible to Toxoplasma gondii infection with enhanced intestinal tissue damage. However, in this thesis it was shown that AhRR-deficiency slightly enhanced Th1 and Tc1 response in the small intestine similar to AhR deficiency in response Toxoplasma gondii infection. These findings may partially explain the intestinal damage observed in AhRR-deficient mice upon parasitic infection. However, the differences in T cell ratios in DSS-induced colitis and Toxoplasma gondii infection in AhRR-deficient mice is not due to T cell intrinsic actions. The necessity of the AhRR in regulating intestinal tissue damage could further be underlined using a Salmonella Typhimurium infection model. The AhRR is required not systemically but locally in the small intestine during bacterial infection. In the small intestine, the AhRR-deficiency leads to a strong Th1 response and is likely to have more profound effect in inducing intestinal damage upon bacterial infection. Furthermore, it was shown that the AhR is required for survival upon Salmonella Typhimurium infection. Unlike the AhRR, the AhR has only a minor influence on Salmonella induced intestinal tissue damage. High serum IFNγ levels in AhR-deficient mice to bacterial challenge correlated with bacterial numbers and disease severity. During infection, the AhR balances extramedullary erythropoiesis by modulating EPO, TPO and IL-6 production. In addition, the AhR is involved in regulating splenic architecture since AhR-deficient mice lose white pulp structure due to decrease in B cell follicles and increase in T cell dislocation in response to Salmonella Typhimurium infection. Moreover, the AhR restrict infection induced hyperactivated immune cell response in spleen by downregulating excess IFNγ expression in T cells and CD69 expression in T cells and myeloid cells. Overall, this study showed that the AhRR influence on T cell differentiation and tissue damage in small intestine is dependent on the disease context and gives novel insights about the processes that are regulated by the AhR during Salmonella Typhimurium infection. | |||||||
| Lizenz: |  Urheberrechtsschutz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät | |||||||
| Dokument erstellt am: | 08.07.2021 | |||||||
| Dateien geändert am: | 08.07.2021 | |||||||
| Promotionsantrag am: | 19.11.2020 | |||||||
| Datum der Promotion: | 24.03.2021 |
