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cGAS-like receptors drive a systemic STING-dependent host response in Drosophila
Xianlong Ai1, Huimin Deng1, Xiaoyan Li1
1Sino-French Hoffmann Institute, State Key Laboratory of Respiratory Disease, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, China.
Cell Reports
|December 17, 2024
Summary
The cGAS-like receptor (cGLR)-STING pathway is crucial for invertebrate antiviral defense. This study reveals its systemic role in Drosophila, impacting host responses and even altering sleep patterns during viral infections.
Area of Science:
- Innate immunity
- Molecular biology
- Virology
Background:
- The cGAS-like receptor (cGLR)-stimulator of interferon genes (STING) pathway is recognized for its role in antiviral defense in invertebrates.
- Its precise function and systemic impact at the organismal level in invertebrates remain largely uncharacterized.
Purpose of the Study:
- To investigate the in vivo activation and organismal contribution of the cGAS-STING pathway in Drosophila during viral infections.
- To elucidate the systemic signaling mechanisms and physiological consequences of this pathway.
Main Methods:
- Utilized STING::GFP knockin reporter Drosophila melanogaster to visualize pathway activation.
- Administered cyclic dinucleotide 3'2'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) and infected flies with viruses.
- Examined tissue-specific reporter gene induction, ectopic gene expression, and behavioral changes (sleep).
Main Results:
- STING::GFP expression was notably induced in the central nervous system, midgut, Malpighian tubules, and genital ducts upon cGAMP injection.
- Systemic STING signaling was triggered by a virus-induced signal, with ectopic cGLR2 expression in the fat body activating STING in distal tissues.
- cGLR1/2-dependent activity was transferred during mating, and viral infection altered sleep in a cGLR1/2- and STING-dependent manner.
Conclusions:
- The cGAS-STING pathway plays a significant role in systemic antiviral responses in Drosophila.
- This pathway mediates communication between infected cells and other tissues, influencing host physiology.
- Cyclic dinucleotide signaling is integral to Drosophila's innate immunity and response to viral pathogens.
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