Selective autophagy in host defense against mycobacterial infection

Leiden Repository

Selective autophagy in host defense against mycobacterial infection

Type: Doctoral Thesis
Title: Selective autophagy in host defense against mycobacterial infection
Author: Zhang, R.
Issue Date: 2018-11-08
Keywords: Autophagy
Tuberculosis
Zebrafish
Mycobacterium marinum
Macrophage
Lc3
Dram1
p62
Optineurin
Abstract: The effective treatment of tuberculosis (TB) remains a major challenge to global health. Drug-resistant Mycobacterium tuberculosis (Mtb) strains and co-infection with HIV further increase the difficulty of controlling TB. Thus, under the current situation, it is essential to develop effective treatment strategies for Mtb infections. Autophagy is a lysosomal degradation process and substantial experimental evidence has demonstrated that autophagy is an important host immune defense mechanism against mycobacterial infection. However, the development of effective therapies requires a better understanding of the interaction between the host and invading pathogens to identify host processes that can be targeted. A useful tool for such studies is the zebrafish model for TB. Zebrafish can be infected with Mycobacterium marinum (Mm), which is closely related to Mtb and causes similar disease characteristics. Taking advantage of the zebrafish TB model, this thesis presents new in vivo evidence for the important function of autophagy to inhibit mycobacterial proliferation inside macrophages. Furthermore, this study supports that stimulating the innate host defense processes that are dependent on the autophagy modulator, Dram1, and the selective autophagy receptors, p62 and Optineurin, could be a useful strategy to explore for adjunctive treatment of antibiotic-resistant TB infections.
Promotor: Supervisor: Meijer A.H. Co-Supervisor: Vaart M. van der, Varela M.
Faculty: Faculty of Science
University: Leiden University
Uri: urn:isbn:9789402812381
Handle: http://hdl.handle.net/1887/66789
 

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