Innate host defense against intracellular pathogens

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Innate host defense against intracellular pathogens

Title: Innate host defense against intracellular pathogens
Author: Vaart, Michiel van der
Publisher: Instute of Biology Leiden (IBL), Molecular Cell Biology, Faculty of Science, Leiden University
Issue Date: 2013-11-14
Keywords: Innate immune system
Toll-like receptors
Bacterial infection
Zebrafish model organism
Abstract: This thesis focuses on the recognition of pathogenic bacteria and the defense mechanisms that are activated during the innate immune response to infection. Detection of pathogens, such as bacteria, viruses, and parasites, depends on receptors that bind to evolutionary conserved structures on their surface. The most extensively studied class of immune receptors is the Toll-like receptor (TLR) family, which signals via adaptor molecules such as myeloid differentiation factor 88 (MyD88) to initiate gene expression and activate the appropriate response upon recognition of a pathogen. We have used the zebrafish as a model organism to study how MyD88 orchestrates the immune response against intracellular bacterial pathogens like Mycobacterium marinum, the causative agent of tuberculosis disease (TB) in fish. We found that several defense mechanisms against TB are highly dependent on MyD88, including autophagy, cytokine and chemokine production, and the generation of microbe killing radicals. These findings in the zebrafish model will hopefully aid in the development of new therapeutic strategies against multi-drug resistant tuberculosis infections.
Description: Promotor: H.P. Spaink, Co-promotor: A.H. Meijer
With summary in Dutch
Faculty: Faculteit der Wiskunde en Natuurwetenschappen
Citation: Vaart, M. van der, 2013, Doctoral thesis, Leiden University
ISBN: 9789462034747

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