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Mycobacterium tuberculosis induces the miR-33 locus to reprogram autophagy and host lipid metabolism.
Ouimet, Mireille; Koster, Stefan; Sakowski, Erik; Ramkhelawon, Bhama; van Solingen, Coen; Oldebeken, Scott; Karunakaran, Denuja; Portal-Celhay, Cynthia; Sheedy, Frederick J; Ray, Tathagat Dutta; Cecchini, Katharine; Zamore, Philip D; Rayner, Katey J; Marcel, Yves L; Philips, Jennifer A; Moore, Kathryn J.
Affiliation
  • Ouimet M; Marc and Ruti Bell Vascular Biology and Disease Program, Leon H. Charney Division of Cardiology, Department of Medicine, New York University Medical Center, New York, New York, USA.
  • Koster S; Division of Infectious Diseases and Immunology, Department of Medicine, New York University Medical Center, New York, New York, USA.
  • Sakowski E; Division of Infectious Diseases and Immunology, Department of Medicine, New York University Medical Center, New York, New York, USA.
  • Ramkhelawon B; Marc and Ruti Bell Vascular Biology and Disease Program, Leon H. Charney Division of Cardiology, Department of Medicine, New York University Medical Center, New York, New York, USA.
  • van Solingen C; Marc and Ruti Bell Vascular Biology and Disease Program, Leon H. Charney Division of Cardiology, Department of Medicine, New York University Medical Center, New York, New York, USA.
  • Oldebeken S; Marc and Ruti Bell Vascular Biology and Disease Program, Leon H. Charney Division of Cardiology, Department of Medicine, New York University Medical Center, New York, New York, USA.
  • Karunakaran D; University of Ottawa Heart Institute and Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ontario, Canada.
  • Portal-Celhay C; Division of Infectious Diseases and Immunology, Department of Medicine, New York University Medical Center, New York, New York, USA.
  • Sheedy FJ; Department of Clinical Medicine, School of Medicine, Trinity College, Dublin, Ireland.
  • Ray TD; Marc and Ruti Bell Vascular Biology and Disease Program, Leon H. Charney Division of Cardiology, Department of Medicine, New York University Medical Center, New York, New York, USA.
  • Cecchini K; RNA Therapeutics Institute, Howard Hughes Medical Institute, and Department of Biochemistry &Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
  • Zamore PD; RNA Therapeutics Institute, Howard Hughes Medical Institute, and Department of Biochemistry &Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
  • Rayner KJ; University of Ottawa Heart Institute and Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ontario, Canada.
  • Marcel YL; University of Ottawa Heart Institute and Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ontario, Canada.
  • Philips JA; Division of Infectious Diseases and Immunology, Department of Medicine, New York University Medical Center, New York, New York, USA.
  • Moore KJ; Marc and Ruti Bell Vascular Biology and Disease Program, Leon H. Charney Division of Cardiology, Department of Medicine, New York University Medical Center, New York, New York, USA.
Nat Immunol ; 17(6): 677-86, 2016 06.
Article in En | MEDLINE | ID: mdl-27089382
ABSTRACT
Mycobacterium tuberculosis (Mtb) survives in macrophages by evading delivery to the lysosome and promoting the accumulation of lipid bodies, which serve as a bacterial source of nutrients. We found that by inducing the microRNA (miRNA) miR-33 and its passenger strand miR-33*, Mtb inhibited integrated pathways involved in autophagy, lysosomal function and fatty acid oxidation to support bacterial replication. Silencing of miR-33 and miR-33* by genetic or pharmacological means promoted autophagy flux through derepression of key autophagy effectors (such as ATG5, ATG12, LC3B and LAMP1) and AMPK-dependent activation of the transcription factors FOXO3 and TFEB, which enhanced lipid catabolism and Mtb xenophagy. These data define a mammalian miRNA circuit used by Mtb to coordinately inhibit autophagy and reprogram host lipid metabolism to enable intracellular survival and persistence in the host.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Autophagy / Tuberculosis / MicroRNAs / Lipid Metabolism / Lysosomes / Macrophages / Mycobacterium tuberculosis Limits: Animals / Humans / Male Language: En Journal: Nat Immunol Journal subject: ALERGIA E IMUNOLOGIA Year: 2016 Type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Autophagy / Tuberculosis / MicroRNAs / Lipid Metabolism / Lysosomes / Macrophages / Mycobacterium tuberculosis Limits: Animals / Humans / Male Language: En Journal: Nat Immunol Journal subject: ALERGIA E IMUNOLOGIA Year: 2016 Type: Article Affiliation country: United States