Publication: TBK-1 Promotes Autophagy-Mediated Antimicrobial Defense by Controlling Autophagosome Maturation
Issued Date
2012-08-24
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ISSN
10974180
10747613
10747613
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2-s2.0-84865357562
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Mahidol University
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SCOPUS
Bibliographic Citation
Immunity. Vol.37, No.2 (2012), 223-234
Suggested Citation
Manohar Pilli, John Arko-Mensah, Marisa Ponpuak, Esteban Roberts, Sharon Master, Michael A. Mandell, Nicolas Dupont, Wojciech Ornatowski, Shanya Jiang, Steven B. Bradfute, Jack Ansgar Bruun, Tom Egil Hansen, Terje Johansen, Vojo Deretic TBK-1 Promotes Autophagy-Mediated Antimicrobial Defense by Controlling Autophagosome Maturation. Immunity. Vol.37, No.2 (2012), 223-234. doi:10.1016/j.immuni.2012.04.015 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/14281
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Title
TBK-1 Promotes Autophagy-Mediated Antimicrobial Defense by Controlling Autophagosome Maturation
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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. © 2012 Elsevier Inc.