Liu, Yunying (2012): The role of the tumor suppressor CYLD in Yersinia enterocolitica infection. Dissertation, LMU München: Faculty of Medicine |
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Abstract
Recent studies have identified the tumor suppressor CYLD as a key regulator of NF -κB, a transcription factor that promotes cell survival and oncogenesis, as well as host defence to infection. In th e pr esent study, we investigated the role of tumor suppressor CYLD in regulation of innate immune responses of mice to Y. enterocolitica infection and for comparison to Salmonella Typhimurium infection . Yersinia is an extracellular multiplying bacterium that ensures its extracellular growth by injecting virulence proteins (Yops) into host cells by the injectisome Ysc-T3SS , which interfere with several signaling pathways (such as MAPK and NF-κB cascades), resulting in the inhibition of phagocytosis, oxidative burst and cytokine production. In contrast, Salmonella Typhimurium is endowed with 2 T3SS which inject effector proteins to induce pathogen uptake and intracellular replication. Surprisingly, we found that Cyld-/- mice were more resistant to Y. enterocolitica than Cyld+/- mice in contrast to Salmonella Typimurium infection which appeared to be CYLD- independent. These results suggest that CYLD acts as a detrimental factor for host survival during early Y. enterocolitica infection. Furthermore, we showed that Yops-mediated inhibition of host defense mechanisms , such as phagocytosis, oxidative burst, NF-κB, cytokine production and p38 activation is attenuated in Cyld-/--phagocytic cells in respect of Cyld+/- cells. Taken together, this study provides for the first time, an empirical demonstration of a pathogen-specific contribution of a tumor suppressor gene and its encoded protein, respectively, CYLD, to infection susceptibility in a manner that seems to be independent of its tumor suppression mechanism. This is another example of the extraordinary complexity of the pathogen/host cell interactions.
Item Type: | Theses (Dissertation, LMU Munich) |
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Keywords: | Cyld,Yersinia enterocolitica,phagocytosis,MAPK,NF-kB,cytokines |
Subjects: | 600 Technology, Medicine 600 Technology, Medicine > 610 Medical sciences and medicine |
Faculties: | Faculty of Medicine |
Language: | English |
Date of oral examination: | 28. February 2012 |
1. Referee: | Rothenfußer, Simon |
MD5 Checksum of the PDF-file: | 531a4a94d08662535ad0a76bdb992e76 |
Signature of the printed copy: | 0700/4 UMD 201 |
ID Code: | 15451 |
Deposited On: | 18. Mar 2013 12:28 |
Last Modified: | 24. Oct 2020 01:23 |