ZFIN ID: ZDB-PUB-180917-2
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.
Date: 2018
Source: Fish & shellfish immunology   83: 238-242 (Journal)
Registered Authors: Figueras, Antonio, Hortle, Elinor, 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.
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.