The helicase DDX41 recognizes the bacterial secondary messengers cyclic di-GMP and cyclic di-AMP to activate a type I interferon immune response
Copyright policy )The helicase DDX41 recognizes the bacterial secondary messengers cyclic di-GMP and cyclic di-AMP to activate a type I interferon immune response
The induction of type I interferons by the bacterial secondary messengers cyclic di-GMP (c-di-GMP) or cyclic di-AMP (c-di-AMP) is dependent on a signaling axis that involves the adaptor STING, the kinase TBK1 and the transcription factor IRF3. Here we identified the heliase DDX41 as a pattern-recognition receptor (PRR) that sensed both c-di-GMP and c-di-AMP. DDX41 specifically and directly interacted with c-di-GMP. Knockdown of DDX41 via short hairpin RNA in mouse or human cells inhibited the induction of genes encoding molecules involved in the innate immune response and resulted in defective activation of STING, TBK1 and IRF3 in response to c-di-GMP or c-di-AMP. Our results suggest a mechanism whereby c-di-GMP and c-di-AMP are detected by DDX41, which forms a complex with STING to signal to TBK1-IRF3 and activate the interferon response.
- Chinese Academy of Sciences China (People's Republic of)
- University of California, Los Angeles United States
- University of California, San Francisco United States
- Chinese Academy of Sciences (中国科学院) China (People's Republic of)
- University of California, Riverside United States
570, Immunology, Pattern Recognition, Protein Serine-Threonine Kinases, Small Interfering, Second Messenger Systems, Cell Line, DEAD-box RNA Helicases, Mice, Receptors, Innate, Animals, Humans, RNA, Small Interfering, Cyclic GMP, Biomedical and Clinical Sciences, Macrophages, Immunity, 500, Membrane Proteins, Biological Sciences, Listeria monocytogenes, Immunity, Innate, Infectious Diseases, Biochemistry and cell biology, Receptors, Pattern Recognition, Interferon Type I, RNA, Interferon Regulatory Factor-3, RNA Interference, Dinucleoside Phosphates, Signal Transduction
570, Immunology, Pattern Recognition, Protein Serine-Threonine Kinases, Small Interfering, Second Messenger Systems, Cell Line, DEAD-box RNA Helicases, Mice, Receptors, Innate, Animals, Humans, RNA, Small Interfering, Cyclic GMP, Biomedical and Clinical Sciences, Macrophages, Immunity, 500, Membrane Proteins, Biological Sciences, Listeria monocytogenes, Immunity, Innate, Infectious Diseases, Biochemistry and cell biology, Receptors, Pattern Recognition, Interferon Type I, RNA, Interferon Regulatory Factor-3, RNA Interference, Dinucleoside Phosphates, Signal Transduction
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