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

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 therap...

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Detalles Bibliográficos
Autores principales: Péan, Claire B., Schiebler, Mark, Tan, Sharon W. S., Sharrock, Jessica A., Kierdorf, Katrin, Brown, Karen P., Maserumule, M. Charlotte, Menezes, Shinelle, Pilátová, Martina, Bronda, Kévin, Guermonprez, Pierre, Stramer, Brian M., Andres Floto, R., Dionne, Marc S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343520/
https://www.ncbi.nlm.nih.gov/pubmed/28262681
http://dx.doi.org/10.1038/ncomms14642
Descripción
Sumario: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.