Regulation of phagocyte triglyceride by a STAT-ATG2 pathway controls mycobacterial infection

Claire B. Péan, Mark Schiebler, Sharon W. S. Tan, Jessica A. Sharrock, Katrin Kierdorf, Karen P. Brown, M. Charlotte Maserumule, Shinelle Menezes, Martina Pilátová, Kévin Bronda, Pierre Guermonprez, Brian M. Stramer, R. Andres Floto and Marc S. Dionne ()
Additional contact information
Claire B. Péan: MRC Centre for Molecular Bacteriology and Infection, Imperial College London
Mark Schiebler: Molecular Immunity Unit, MRC Laboratory of Molecular Biology
Sharon W. S. Tan: Centre for Molecular and Cellular Biology of Inflammation, School of Medicine, King’s College London
Jessica A. Sharrock: MRC Centre for Molecular Bacteriology and Infection, Imperial College London
Katrin Kierdorf: MRC Centre for Molecular Bacteriology and Infection, Imperial College London
Karen P. Brown: Molecular Immunity Unit, MRC Laboratory of Molecular Biology
M. Charlotte Maserumule: Molecular Immunity Unit, MRC Laboratory of Molecular Biology
Shinelle Menezes: Centre for Molecular and Cellular Biology of Inflammation, School of Medicine, King’s College London
Martina Pilátová: King’s College London
Kévin Bronda: Centre for Molecular and Cellular Biology of Inflammation, School of Medicine, King’s College London
Pierre Guermonprez: Centre for Molecular and Cellular Biology of Inflammation, School of Medicine, King’s College London
Brian M. Stramer: King’s College London
R. Andres Floto: Molecular Immunity Unit, MRC Laboratory of Molecular Biology
Marc S. Dionne: MRC Centre for Molecular Bacteriology and Infection, Imperial College London

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: 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.

Date: 2017
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms14642 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14642

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms14642

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().