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TBK-1 promotes autophagy-mediated antimicrobial defense by controlling autophagosome maturation.
- Source :
-
Immunity [Immunity] 2012 Aug 24; Vol. 37 (2), pp. 223-34. - Publication Year :
- 2012
-
Abstract
- Autophagy is a fundamental biological process of the eukaryotic cell contributing to diverse cellular and physiological functions including cell-autonomous defense against intracellular pathogens. Here, we screened the Rab family of membrane trafficking regulators for effects on autophagic elimination of Mycobacterium tuberculosis var. bovis BCG and found that Rab8b and its downstream interacting partner, innate immunity regulator TBK-1, are required for autophagic elimination of mycobacteria in macrophages. TBK-1 was necessary for autophagic maturation. TBK-1 coordinated assembly and function of the autophagic machinery and phosphorylated the autophagic adaptor p62 (sequestosome 1) on Ser-403, a residue essential for its role in autophagic clearance. A key proinflammatory cytokine, IL-1β, induced autophagy leading to autophagic killing of mycobacteria in macrophages, and this IL-1β activity was dependent on TBK-1. Thus, TBK-1 is a key regulator of immunological autophagy and is responsible for the maturation of autophagosomes into lytic bactericidal organelles.<br /> (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Subjects :
- Adaptor Proteins, Signal Transducing immunology
Adaptor Proteins, Signal Transducing metabolism
Animals
Autophagy-Related Protein 7
Green Fluorescent Proteins
HeLa Cells
Heat-Shock Proteins immunology
Heat-Shock Proteins metabolism
Humans
Interleukin-1beta immunology
Interleukin-1beta metabolism
Macrophages drug effects
Macrophages metabolism
Mice
Microscopy, Confocal
Microtubule-Associated Proteins antagonists & inhibitors
Microtubule-Associated Proteins genetics
Mycobacterium bovis immunology
Phagosomes drug effects
Phagosomes immunology
Phagosomes metabolism
Phosphorylation
Protein Serine-Threonine Kinases antagonists & inhibitors
Protein Serine-Threonine Kinases metabolism
RNA, Small Interfering
Sequestosome-1 Protein
Serine immunology
Serine metabolism
Tuberculosis immunology
rab GTP-Binding Proteins genetics
Autophagy immunology
Macrophages immunology
Protein Serine-Threonine Kinases immunology
rab GTP-Binding Proteins immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4180
- Volume :
- 37
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Immunity
- Publication Type :
- Academic Journal
- Accession number :
- 22921120
- Full Text :
- https://doi.org/10.1016/j.immuni.2012.04.015