TBK-1 Promotes Autophagy-Mediated Antimicrobial Defense by Controlling Autophagosome Maturation

被引：528

作者：

Pilli, Manohar ^{[1
]}

Arko-Mensah, John ^{[1
]}

Ponpuak, Marisa ^{[1
,2
]}

Roberts, Esteban ^{[1
]}

Master, Sharon ^{[1
]}

Mandell, Michael A. ^{[1
]}

Dupont, Nicolas ^{[1
]}

Ornatowski, Wojciech ^{[1
]}

Jiang, Shanya ^{[1
]}

Bradfute, Steven B. ^{[1
]}

Bruun, Jack-Ansgar ^{[3
]}

Hansen, Tom Egil ^{[3
]}

Johansen, Terje ^{[3
]}

Deretic, Vojo ^{[1
]}

机构：

[1] Univ New Mexico, Hlth Sci Ctr, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA

[2] Mahidol Univ, Fac Sci, Dept Microbiol, Bangkok 10400, Thailand

[3] Univ Tromso, Inst Med Biol, Mol Canc Res Grp, N-9037 Tromso, Norway

来源：

IMMUNITY | 2012年 / 37卷 / 02期

基金：

美国国家卫生研究院;

关键词：

MUTANT HUNTINGTIN; KAPPA-B; PROTEINS; INNATE; CELL; IMMUNITY; ADAPTER; BINDING; PHOSPHORYLATION; RESTRICTS;

D O I：

10.1016/j.immuni.2012.04.015

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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-1 beta 13, induced autophagy leading to autophagic killing of mycobacteria in macrophages, and this IL-1 beta 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.

引用

页码：223 / 234

页数：12

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