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dc.contributor.authorManohar Pillien_US
dc.contributor.authorJohn Arko-Mensahen_US
dc.contributor.authorMarisa Ponpuaken_US
dc.contributor.authorEsteban Robertsen_US
dc.contributor.authorSharon Masteren_US
dc.contributor.authorMichael A. Mandellen_US
dc.contributor.authorNicolas Duponten_US
dc.contributor.authorWojciech Ornatowskien_US
dc.contributor.authorShanya Jiangen_US
dc.contributor.authorSteven B. Bradfuteen_US
dc.contributor.authorJack Ansgar Bruunen_US
dc.contributor.authorTom Egil Hansenen_US
dc.contributor.authorTerje Johansenen_US
dc.contributor.authorVojo Dereticen_US
dc.contributor.otherUniversity of New Mexico Health Sciences Centeren_US
dc.contributor.otherMahidol Universityen_US
dc.contributor.otherUniversitetet i Tromsoen_US
dc.identifier.citationImmunity. Vol.37, No.2 (2012), 223-234en_US
dc.description.abstractAutophagy 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.en_US
dc.rightsMahidol Universityen_US
dc.subjectImmunology and Microbiologyen_US
dc.titleTBK-1 Promotes Autophagy-Mediated Antimicrobial Defense by Controlling Autophagosome Maturationen_US
Appears in Collections:Scopus 2011-2015

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