Crosstalk between the cGAS DNA sensor and beclin-1 autophagy protein shapes innate antimicrobial immune responses

Qiming Liang, Gil Ju Seo, Youn Jung Choi, Mi Jeong Kwak, Jianning Ge, Mary A. Rodgers, Mude Shi, Benjamin J. Leslie, Karl Peter Hopfner, Taekjip Ha, Byung Ha Oh, Jae U. Jung

Research output: Contribution to journalArticle

Abstract

Robust immune responses are essential for eliminating pathogens but must be metered to avoid prolonged immune activation and potential host damage. Upon recognition of microbial DNA, the cytosolic DNA sensor cyclic GMP-AMP (cGAMP) synthetase (cGAS) produces the second messenger cGAMP to initiate the stimulator of interferon genes (STING) pathway and subsequent interferon (IFN) production. We report that the direct interaction between cGAS and the Beclin-1 autophagy protein not only suppresses cGAMP synthesis to halt IFN production upon double-stranded DNA (dsDNA) stimulation or herpes simplex virus-1 infection, but also enhances autophagy-mediated degradation of cytosolic pathogen DNA to prevent excessive cGAS activation and persistent immune stimulation. Specifically, this interaction releases Rubicon, a negative autophagy regulator, from the Beclin-1 complex, activating phosphatidylinositol 3-kinase class III activity and thereby inducing autophagy to remove cytosolic pathogen DNA. Thus, the cGAS-Beclin-1 interaction shapes innate immune responses by regulating both cGAMP production and autophagy, resulting in well-balanced antimicrobial immune responses.

Original languageEnglish (US)
Pages (from-to)228-238
Number of pages11
JournalCell Host and Microbe
Volume15
Issue number2
DOIs
StatePublished - Feb 12 2014

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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    Liang, Q., Seo, G. J., Choi, Y. J., Kwak, M. J., Ge, J., Rodgers, M. A., Shi, M., Leslie, B. J., Hopfner, K. P., Ha, T., Oh, B. H., & Jung, J. U. (2014). Crosstalk between the cGAS DNA sensor and beclin-1 autophagy protein shapes innate antimicrobial immune responses. Cell Host and Microbe, 15(2), 228-238. https://doi.org/10.1016/j.chom.2014.01.009