TBK-1 Promotes Autophagy-Mediated Antimicrobial Defense by Controlling Autophagosome Maturation
| Autor: | Jack-Ansgar Bruun, Steven B. Bradfute, Sharon Master, John Arko-Mensah, Manohar Pilli, Nicolas Dupont, Esteban A. Roberts, Wojciech Ornatowski, Michael A. Mandell, Marisa Ponpuak, Tom Egil Hansen, Vojo Deretic, Terje Johansen, Shanya Jiang |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Sequestosome-1 Protein
Autophagosome maturation Green Fluorescent Proteins Interleukin-1beta Immunology Protein Serine-Threonine Kinases Biology Autophagy-Related Protein 7 Article Mice 03 medical and health sciences 0302 clinical medicine Sequestosome 1 Phagosomes Autophagy Serine Animals Humans Tuberculosis Immunology and Allergy Phosphorylation RNA Small Interfering education Heat-Shock Proteins Adaptor Proteins Signal Transducing 030304 developmental biology Phagosome 0303 health sciences education.field_of_study Microscopy Confocal Innate immune system Macrophages Mycobacterium bovis 3. Good health Cell biology Infectious Diseases rab GTP-Binding Proteins Rab Microtubule-Associated Proteins 030217 neurology & neurosurgery HeLa Cells |
| Zdroj: | Immunity. 37:223-234 |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/j.immuni.2012.04.015 |
| Popis: | SummaryAutophagy 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|