cGAS-like receptors drive a systemic STING-dependent host response in Drosophila

Summary: cGAS-like receptor (cGLR)-stimulator of interferon genes (STING) recently emerged as an important pathway controlling viral infections in invertebrates. However, its exact contribution at the organismal level remains uncharacterized. Here, we use STING::GFP knockin reporter Drosophila flies...

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Main Authors: Xianlong Ai, Huimin Deng, Xiaoyan Li, Ziming Wei, Yuqiang Chen, Ting Yin, Junhui Zhang, Jingxian Huang, Haoming Li, Xiaoqing Lin, Long Tan, Di Chen, Xiaohan Zhang, Xiuqing Zhang, Carine Meignin, Jean-Luc Imler, Hua Cai
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Cell Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2211124724014323
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author Xianlong Ai
Huimin Deng
Xiaoyan Li
Ziming Wei
Yuqiang Chen
Ting Yin
Junhui Zhang
Jingxian Huang
Haoming Li
Xiaoqing Lin
Long Tan
Di Chen
Xiaohan Zhang
Xiuqing Zhang
Carine Meignin
Jean-Luc Imler
Hua Cai
author_facet Xianlong Ai
Huimin Deng
Xiaoyan Li
Ziming Wei
Yuqiang Chen
Ting Yin
Junhui Zhang
Jingxian Huang
Haoming Li
Xiaoqing Lin
Long Tan
Di Chen
Xiaohan Zhang
Xiuqing Zhang
Carine Meignin
Jean-Luc Imler
Hua Cai
author_sort Xianlong Ai
collection DOAJ
description Summary: cGAS-like receptor (cGLR)-stimulator of interferon genes (STING) recently emerged as an important pathway controlling viral infections in invertebrates. However, its exact contribution at the organismal level remains uncharacterized. Here, we use STING::GFP knockin reporter Drosophila flies to document activation of the pathway in vivo. Four tissues strongly respond to injection of the cyclic dinucleotide 3′2′- cyclic guanosine monophosphate-adenosine monophosphate (cGAMP): the central nervous system, midgut, Malpighian tubules, and genital ducts. The pattern of STING::GFP induction in flies injected with 3′2′-cGAMP or infected by two viruses with different tropism suggests that the reporter is induced by a systemic signal produced in virus-infected cells. Accordingly, ectopic expression of cGLR2 in the fat body induces STING signaling in remote tissues and a cGLR1/2-dependent activity is transferred to females during mating. Furthermore, viral infection can alter sleep in a cGLR1/2- and STING-dependent manner. Altogether, our results reveal a contribution of cyclic dinucleotide signaling to a systemic host response to viral infection in Drosophila.
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spelling doaj-art-a230ef71bbf54e19a453acf574bedefe2025-08-20T02:49:01ZengElsevierCell Reports2211-12472024-12-01431211508110.1016/j.celrep.2024.115081cGAS-like receptors drive a systemic STING-dependent host response in DrosophilaXianlong Ai0Huimin Deng1Xiaoyan Li2Ziming Wei3Yuqiang Chen4Ting Yin5Junhui Zhang6Jingxian Huang7Haoming Li8Xiaoqing Lin9Long Tan10Di Chen11Xiaohan Zhang12Xiuqing Zhang13Carine Meignin14Jean-Luc Imler15Hua Cai16Sino-French Hoffmann Institute, State Key Laboratory of Respiratory Disease, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, ChinaSino-French Hoffmann Institute, State Key Laboratory of Respiratory Disease, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, ChinaSino-French Hoffmann Institute, State Key Laboratory of Respiratory Disease, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, ChinaSino-French Hoffmann Institute, State Key Laboratory of Respiratory Disease, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, ChinaSino-French Hoffmann Institute, State Key Laboratory of Respiratory Disease, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, ChinaSino-French Hoffmann Institute, State Key Laboratory of Respiratory Disease, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, ChinaSino-French Hoffmann Institute, State Key Laboratory of Respiratory Disease, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, ChinaSino-French Hoffmann Institute, State Key Laboratory of Respiratory Disease, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, ChinaSino-French Hoffmann Institute, State Key Laboratory of Respiratory Disease, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, ChinaSino-French Hoffmann Institute, State Key Laboratory of Respiratory Disease, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, ChinaSino-French Hoffmann Institute, State Key Laboratory of Respiratory Disease, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, ChinaSino-French Hoffmann Institute, State Key Laboratory of Respiratory Disease, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, ChinaGuangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, ChinaGuangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, ChinaUniversité de Strasbourg, CNRS UPR9022, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, FranceSino-French Hoffmann Institute, State Key Laboratory of Respiratory Disease, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, China; Université de Strasbourg, CNRS UPR9022, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France; Corresponding authorSino-French Hoffmann Institute, State Key Laboratory of Respiratory Disease, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, China; Corresponding authorSummary: cGAS-like receptor (cGLR)-stimulator of interferon genes (STING) recently emerged as an important pathway controlling viral infections in invertebrates. However, its exact contribution at the organismal level remains uncharacterized. Here, we use STING::GFP knockin reporter Drosophila flies to document activation of the pathway in vivo. Four tissues strongly respond to injection of the cyclic dinucleotide 3′2′- cyclic guanosine monophosphate-adenosine monophosphate (cGAMP): the central nervous system, midgut, Malpighian tubules, and genital ducts. The pattern of STING::GFP induction in flies injected with 3′2′-cGAMP or infected by two viruses with different tropism suggests that the reporter is induced by a systemic signal produced in virus-infected cells. Accordingly, ectopic expression of cGLR2 in the fat body induces STING signaling in remote tissues and a cGLR1/2-dependent activity is transferred to females during mating. Furthermore, viral infection can alter sleep in a cGLR1/2- and STING-dependent manner. Altogether, our results reveal a contribution of cyclic dinucleotide signaling to a systemic host response to viral infection in Drosophila.http://www.sciencedirect.com/science/article/pii/S2211124724014323CP: Immunology
spellingShingle Xianlong Ai
Huimin Deng
Xiaoyan Li
Ziming Wei
Yuqiang Chen
Ting Yin
Junhui Zhang
Jingxian Huang
Haoming Li
Xiaoqing Lin
Long Tan
Di Chen
Xiaohan Zhang
Xiuqing Zhang
Carine Meignin
Jean-Luc Imler
Hua Cai
cGAS-like receptors drive a systemic STING-dependent host response in Drosophila
Cell Reports
CP: Immunology
title cGAS-like receptors drive a systemic STING-dependent host response in Drosophila
title_full cGAS-like receptors drive a systemic STING-dependent host response in Drosophila
title_fullStr cGAS-like receptors drive a systemic STING-dependent host response in Drosophila
title_full_unstemmed cGAS-like receptors drive a systemic STING-dependent host response in Drosophila
title_short cGAS-like receptors drive a systemic STING-dependent host response in Drosophila
title_sort cgas like receptors drive a systemic sting dependent host response in drosophila
topic CP: Immunology
url http://www.sciencedirect.com/science/article/pii/S2211124724014323
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