Open Close
Reference
Citation
Péan, C.B., Schiebler, M., Tan, S.W., Sharrock, J.A., Kierdorf, K., Brown, K.P., Maserumule, M.C., Menezes, S., Pilátová, M., Bronda, K., Guermonprez, P., Stramer, B.M., Andres Floto, R., Dionne, M.S. (2017). Regulation of phagocyte triglyceride by a STAT-ATG2 pathway controls mycobacterial infection.  Nat. Commun. 8(): 14642.
FlyBase ID
FBrf0234962
Publication Type
Research paper
Abstract

Mycobacterium tuberculosis remains a global threat to human health, yet the molecular mechanisms regulating immunity remain poorly understood. Cytokines can promote or inhibit mycobacterial survival inside macrophages and the underlying mechanisms represent potential targets for host-directed therapies. Here we show that cytokine-STAT signalling promotes mycobacterial survival within macrophages by deregulating lipid droplets via ATG2 repression. In Drosophila infected with Mycobacterium marinum, mycobacterium-induced STAT activity triggered by unpaired-family cytokines reduces Atg2 expression, permitting deregulation of lipid droplets. Increased Atg2 expression or reduced macrophage triglyceride biosynthesis, normalizes lipid deposition in infected phagocytes and reduces numbers of viable intracellular mycobacteria. In human macrophages, addition of IL-6 promotes mycobacterial survival and BCG-induced lipid accumulation by a similar, but probably not identical, mechanism. Our results reveal Atg2 regulation as a mechanism by which cytokines can control lipid droplet homeostasis and consequently resistance to mycobacterial infection in Drosophila.

PubMed ID
PubMed Central ID
PMC5343520 (PMC) (EuropePMC)
Associated Information
Comments
Associated Files
Other Information
Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Nat. Commun.
    Title
    Nature communications
    ISBN/ISSN
    2041-1723
    Data From Reference
    Aberrations (1)
    Alleles (10)
    Genes (20)
    Human Disease Models (1)
    Insertions (1)
    Transgenic Constructs (7)