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.
journal_name
Immunityjournal_title
Immunityauthors
Pilli M,Arko-Mensah J,Ponpuak M,Roberts E,Master S,Mandell MA,Dupont N,Ornatowski W,Jiang S,Bradfute SB,Bruun JA,Hansen TE,Johansen T,Deretic Vdoi
10.1016/j.immuni.2012.04.015subject
Has Abstractpub_date
2012-08-24 00:00:00pages
223-34issue
2eissn
1074-7613issn
1097-4180pii
S1074-7613(12)00330-5journal_volume
37pub_type
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