Kasper, Christoph Alexander.
Amplifying the innate immune response : cell-cell propagation of proinflammatory signals during bacterial infection.
PhD Thesis, University of Basel,
Faculty of Science.
Official URL: http://edoc.unibas.ch/diss/DissB_9884
The enteroinvasive bacterium Shigella flexneri uses multiple secreted effector proteins to downregulate interleukin-8 (IL-8) expression in infected epithelial cells. Nevertheless, massive IL-8 secretion is observed in shigellosis. In this thesis, a novel host mechanism of cell-cell communication that circumvents the effectors and strongly amplifies IL-8 expression during bacterial infection is reported. By monitoring proinflammatory signals at the single-cell level during Shigella infection, we found that activation of the transcription factor NF-kappaB and the MAP kinases JNK, ERK and p38 rapidly propagates from infected to uninfected adjacent cells leading to massive IL-8 production by uninfected bystander cells. Bystander IL-8 production was also observed during Listeria monocytogenes and Salmonella typhimurium infection. It was reproduced by microinjection of the Nod1 ligand L-Ala-D-gamma-Glu-meso-diaminopimelic acid and blocked by gap junction inhibitors. Thus, a novel gap junction-mediated mechanism of cell-cell communication was identified that broadly amplifies innate immunity against bacterial infection by rapidly spreading proinflammatory signals to yet uninfected cells.
|Committee Members:||Dehio, Christoph|
|Faculties and Departments:||05 Faculty of Science > Departement Biozentrum > Infection Biology > Molecular Microbiology (Arrieumerlou)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||156 S.|
|Last Modified:||30 Jun 2016 10:48|
|Deposited On:||07 May 2012 10:17|
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