TBK-1 promotes autophagy-mediated antimicrobial defense by controlling autophagosome maturation. Academic Article uri icon

start page

  • 223

end page

  • 234

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-1?, induced autophagy leading to autophagic killing of mycobacteria in macrophages, and this IL-1? 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.Copyright © 2012 Elsevier Inc. All rights reserved.

date/time value

  • 2012

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2012.04.015

PubMed Identifier

  • 22921120

volume

  • 37

number

  • 2

keywords

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Autophagy
  • Green Fluorescent Proteins
  • HeLa Cells
  • Heat-Shock Proteins
  • Humans
  • Interleukin-1beta
  • Macrophages
  • Mice
  • Microscopy, Confocal
  • Microtubule-Associated Proteins
  • Mycobacterium bovis
  • Phagosomes
  • Phosphorylation
  • Protein-Serine-Threonine Kinases
  • RNA, Small Interfering
  • Serine
  • Tuberculosis
  • rab GTP-Binding Proteins