[HTML][HTML] Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages
MG Gutierrez, SS Master, SB Singh, GA Taylor… - Cell, 2004 - cell.com
Cell, 2004•cell.com
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 …
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 …
Abstract
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-γ induced autophagy in macrophages, and so did transfection with LRG-47, an effector of IFN-γ 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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