PUBLICATION

Analysis of mycobacterial infection-induced changes to host lipid metabolism in a zebrafish infection model reveals a conserved role for LDLR in infection susceptibility

Authors
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.
ID
ZDB-PUB-180917-2
Date
2018
Source
Fish & shellfish immunology   83: 238-242 (Journal)
Registered Authors
Figueras, Antonio, Hortle, Elinor, Novoa, Beatriz, Oehlers, Stefan
Keywords
Granuloma, Lipid, Mycobacterium, Pathogenesis, Zebrafish
MeSH Terms
  • Animals
  • 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
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
30219383 Full text @ Fish Shellfish Immunol.
Abstract
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
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
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Mapping