Analysis of mycobacterial infection-induced changes to host lipid metabolism in a zebrafish infection model reveals a conserved role for LDLR in infection susceptibility
- Johansen, M.D., Hortle, E., Kasparian, J.A., Romero, A., Novoa, B., Figueras, A., Britton, W.J., de Silva, K., Purdie, A.C., Oehlers, S.H.
- Fish & shellfish immunology 83: 238-242 (Journal)
- Registered Authors
- Figueras, Antonio, Hortle, Elinor, Oehlers, Stefan
- Granuloma, Lipid, Mycobacterium, Pathogenesis, Zebrafish
- MeSH Terms
- Cholesterol, LDL/metabolism
- Disease Models, Animal
- Embryo, Nonmammalian
- Fish Diseases/metabolism*
- Lipid Metabolism
- Mycobacterium Infections, Nontuberculous/metabolism*
- Mycobacterium Infections, Nontuberculous/veterinary
- Receptors, LDL/genetics
- Receptors, LDL/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- 30219383 Full text @ Fish Shellfish Immunol.
Johansen, M.D., Hortle, E., Kasparian, J.A., Romero, A., Novoa, B., Figueras, A., Britton, W.J., de Silva, K., Purdie, A.C., Oehlers, S.H. (2018) Analysis of mycobacterial infection-induced changes to host lipid metabolism in a zebrafish infection model reveals a conserved role for LDLR in infection susceptibility. Fish & shellfish immunology. 83:238-242.
Changes to lipid metabolism are well-characterised consequences of human tuberculosis infection but their functional relevance are not clearly elucidated in these or other host-mycobacterial systems. The zebrafish-Mycobacterium marinum infection model is used extensively to model many aspects of human-M. tuberculosis pathogenesis but has not been widely used to study the role of infection-induced lipid metabolism. We find mammalian mycobacterial infection-induced alterations in host Low Density Lipoprotein metabolism are conserved in the zebrafish model of mycobacterial pathogenesis. Depletion of LDLR, a key lipid metabolism node, decreased M. marinum burden, and corrected infection-induced altered lipid metabolism resulting in decreased LDL and reduced the rate of macrophage transformation into foam cells. Our results demonstrate a conserved role for infection-induced alterations to host lipid metabolism, and specifically the LDL-LDLR axis, across host-mycobacterial species pairings.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes