Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages
- PMID: 15607973
- DOI: 10.1016/j.cell.2004.11.038
Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages
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-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.
Similar articles
-
IL-27 inhibits IFN-γ induced autophagy by concomitant induction of JAK/PI3 K/Akt/mTOR cascade and up-regulation of Mcl-1 in Mycobacterium tuberculosis H37Rv infected macrophages.Int J Biochem Cell Biol. 2014 Oct;55:335-47. doi: 10.1016/j.biocel.2014.08.022. Epub 2014 Sep 4. Int J Biochem Cell Biol. 2014. PMID: 25194337
-
Phosphoinositides in phagolysosome and autophagosome biogenesis.Biochem Soc Symp. 2007;(74):141-8. doi: 10.1042/BSS0740141. Biochem Soc Symp. 2007. PMID: 17233587 Review.
-
Mycobacterium tuberculosis inhibition of phagolysosome biogenesis and autophagy as a host defence mechanism.Cell Microbiol. 2006 May;8(5):719-27. doi: 10.1111/j.1462-5822.2006.00705.x. Cell Microbiol. 2006. PMID: 16611222 Review.
-
Cholesterol depletion in Mycobacterium avium-infected macrophages overcomes the block in phagosome maturation and leads to the reversible sequestration of viable mycobacteria in phagolysosome-derived autophagic vacuoles.Cell Microbiol. 2006 Feb;8(2):242-56. doi: 10.1111/j.1462-5822.2005.00617.x. Cell Microbiol. 2006. PMID: 16441435
-
Role of phosphatidylinositol 3-kinase and Rab5 effectors in phagosomal biogenesis and mycobacterial phagosome maturation arrest.J Cell Biol. 2001 Aug 6;154(3):631-44. doi: 10.1083/jcb.200106049. J Cell Biol. 2001. PMID: 11489920 Free PMC article.
Cited by
-
Tuberculosis-diabetes comorbidities: Mechanistic insights for clinical considerations and treatment challenges.World J Diabetes. 2024 May 15;15(5):853-866. doi: 10.4239/wjd.v15.i5.853. World J Diabetes. 2024. PMID: 38766427 Free PMC article. Review.
-
Vaccinia virus subverts xenophagy through phosphorylation and nuclear targeting of p62.J Cell Biol. 2024 Jun 3;223(6):e202104129. doi: 10.1083/jcb.202104129. Epub 2024 May 6. J Cell Biol. 2024. PMID: 38709216 Free PMC article.
-
A host-directed oxadiazole compound potentiates antituberculosis treatment via zinc poisoning in human macrophages and in a mouse model of infection.PLoS Biol. 2024 Apr 29;22(4):e3002259. doi: 10.1371/journal.pbio.3002259. eCollection 2024 Apr. PLoS Biol. 2024. PMID: 38683873 Free PMC article.
-
Establishment of an in vitro model of monocyte-like THP-1 cells for trained immunity induced by bacillus Calmette-Guérin.BMC Microbiol. 2024 Apr 20;24(1):130. doi: 10.1186/s12866-024-03191-x. BMC Microbiol. 2024. PMID: 38643095 Free PMC article.
-
The role of ESAT-6 in tuberculosis immunopathology.Front Immunol. 2024 Apr 3;15:1383098. doi: 10.3389/fimmu.2024.1383098. eCollection 2024. Front Immunol. 2024. PMID: 38633252 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous