2. Academic Validation
  3. STING directly activates autophagy to tune the innate immune response

STING directly activates autophagy to tune the innate immune response

  • Cell Death Differ. 2019 Sep;26(9):1735-1749. doi: 10.1038/s41418-018-0251-z.
Dong Liu 1 2,  Hao Wu 1,  Chenguang Wang 3,  Yanjun Li 1,  Huabin Tian 2 4,  Sami Siraj 1 5,  Sheikh Arslan Sehgal 1 2,  Xiaohui Wang 1,  Jun Wang 1,  Yingli Shang 6,  Zhengfan Jiang 3,  Lei Liu 7,  Quan Chen 8 9 10
Affiliations

Affiliations

  • 1 State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
  • 2 University of Chinese Academy of Sciences, Beijing, China.
  • 3 College of Life Sciences, Peking University, Beijing, China.
  • 4 Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
  • 5 Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan.
  • 6 Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Veterinary Medicine, Shandong Agricultural University, Tai'an, China.
  • 7 State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. [email protected].
  • 8 State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. [email protected].
  • 9 University of Chinese Academy of Sciences, Beijing, China. [email protected].
  • 10 College of Life Sciences, Nankai University, Tianjin, China. [email protected].
PMID: 30568238 DOI: 10.1038/s41418-018-0251-z
Abstract

STING (stimulator of interferon genes) is a central molecule that binds to cyclic dinucleotides produced by the Cyclic GMP-AMP Synthase (cGAS) to activate innate immunity against microbial Infection. Here we report that STING harbors classic LC-3 interacting regions (LIRs) and mediates Autophagy through its direct interaction with LC3. We observed that poly(dA:dT), cGAMP, and HSV-1 induced STING-dependent Autophagy and degradation of STING immediately after TBK1 activation. STING induces non-canonical Autophagy that is dependent on ATG5, whereas other Autophagy regulators such as Beclin1, Atg9a, ULK1, and p62 are dispensable. LIR mutants of STING abolished its interaction with LC3 and its activation of Autophagy. Also, mutants that abolish STING dimerization and cGAMP-binding diminished the STING-LC3 interaction and subsequent Autophagy, suggesting that STING activation is indispensable for Autophagy induction. Our results thus uncover dual functions of STING in activating the immune response and Autophagy, and suggest that STING is involved in ensuring a measured innate immune response.

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