In the last decade the study of the innate immune system has gained renewed scientific momentum as a result of the discovery of essential receptor families, such as the Toll-like receptor (TLR)... Show moreIn the last decade the study of the innate immune system has gained renewed scientific momentum as a result of the discovery of essential receptor families, such as the Toll-like receptor (TLR) family, that are required for pathogen recognition. These receptors detect specific molecular structures of microorganisms and in turn are able to trigger host immune responses. The work described in this thesis focuses on the use of the zebrafish embryo as a model to study the vertebrate immune system in order to gain new insights into the mechanisms of innate immune defence against bacterial infections and TLR signalling. Making use of a Salmonella infection model in combination with microarray technology and gene knock-down studies we were able to thoroughly characterize the embryonic host transcriptome response to a bacterial infection. Furthermore, we have demonstrated important functions for key signalling molecules in the innate immune response, including Tlr5, MyD88 and Traf6 and discovered new downstream targets of the TLR signalling pathway. The data presented here will enable in-depth functional follow-up studies that will provide new insights into the mechanisms of innate immune defence systems. This, in combination with future applications of zebrafish embryo infection models in high-throughput compound screens, holds much promise for the discovery of novel anti-microbial and anti-inflammatory drugs. Show less
