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Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages.

Publication ,  Journal Article
Gutierrez, MG; Master, SS; Singh, SB; Taylor, GA; Colombo, MI; Deretic, V
Published in: Cell
December 17, 2004

Mycobacterium tuberculosis is an intracellular pathogen persisting within phagosomes through interference with phagolysosome biogenesis. Here we show that stimulation of autophagic pathways in macrophages causes mycobacterial phagosomes to mature into phagolysosomes. Physiological induction of autophagy or its pharmacological stimulation by rapamycin resulted in mycobacterial phagosome colocalization with the autophagy effector LC3, an elongation factor in autophagosome formation. Autophagy stimulation increased phagosomal colocalization with Beclin-1, a subunit of the phosphatidylinositol 3-kinase hVPS34, necessary for autophagy and a target for mycobacterial phagosome maturation arrest. Induction of autophagy suppressed intracellular survival of mycobacteria. IFN-gamma induced autophagy in macrophages, and so did transfection with LRG-47, an effector of IFN-gamma required for antimycobacterial action. These findings demonstrate that autophagic pathways can overcome the trafficking block imposed by M. tuberculosis. Autophagy, which is a hormonally, developmentally, and, as shown here, immunologically regulated process, represents an underappreciated innate defense mechanism for control of intracellular pathogens.

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Published In

Cell

DOI

ISSN

0092-8674

Publication Date

December 17, 2004

Volume

119

Issue

6

Start / End Page

753 / 766

Location

United States

Related Subject Headings

  • Sirolimus
  • Proteins
  • Phosphatidylinositol 3-Kinases
  • Phagosomes
  • Mycobacterium tuberculosis
  • Microscopy, Electron, Transmission
  • Mice
  • Macrophages
  • Lysosomes
  • Interferon-gamma
 

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Gutierrez, M. G., Master, S. S., Singh, S. B., Taylor, G. A., Colombo, M. I., & Deretic, V. (2004). Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell, 119(6), 753–766. https://doi.org/10.1016/j.cell.2004.11.038
Gutierrez, Maximiliano G., Sharon S. Master, Sudha B. Singh, Gregory A. Taylor, Maria I. Colombo, and Vojo Deretic. “Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages.Cell 119, no. 6 (December 17, 2004): 753–66. https://doi.org/10.1016/j.cell.2004.11.038.
Gutierrez MG, Master SS, Singh SB, Taylor GA, Colombo MI, Deretic V. Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell. 2004 Dec 17;119(6):753–66.
Gutierrez, Maximiliano G., et al. “Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages.Cell, vol. 119, no. 6, Dec. 2004, pp. 753–66. Pubmed, doi:10.1016/j.cell.2004.11.038.
Gutierrez MG, Master SS, Singh SB, Taylor GA, Colombo MI, Deretic V. Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell. 2004 Dec 17;119(6):753–766.
Journal cover image

Published In

Cell

DOI

ISSN

0092-8674

Publication Date

December 17, 2004

Volume

119

Issue

6

Start / End Page

753 / 766

Location

United States

Related Subject Headings

  • Sirolimus
  • Proteins
  • Phosphatidylinositol 3-Kinases
  • Phagosomes
  • Mycobacterium tuberculosis
  • Microscopy, Electron, Transmission
  • Mice
  • Macrophages
  • Lysosomes
  • Interferon-gamma