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The role of the tumor suppressor CYLD in Yersinia enterocolitica infection
The role of the tumor suppressor CYLD in Yersinia enterocolitica infection
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.
Cyld,Yersinia enterocolitica,phagocytosis,MAPK,NF-kB,cytokines
Liu, Yunying
2012
English
Universitätsbibliothek der Ludwig-Maximilians-Universität München
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.