cGAS-like receptors drive a systemic STING-dependent host response in Drosophila
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
Affiliations
Xianlong Ai
Sino-French Hoffmann Institute, State Key Laboratory of Respiratory Disease, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, China
Huimin Deng
Sino-French Hoffmann Institute, State Key Laboratory of Respiratory Disease, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, China
Xiaoyan Li
Sino-French Hoffmann Institute, State Key Laboratory of Respiratory Disease, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, China
Ziming Wei
Sino-French Hoffmann Institute, State Key Laboratory of Respiratory Disease, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, China
Yuqiang Chen
Sino-French Hoffmann Institute, State Key Laboratory of Respiratory Disease, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, China
Ting Yin
Sino-French Hoffmann Institute, State Key Laboratory of Respiratory Disease, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, China
Junhui Zhang
Sino-French Hoffmann Institute, State Key Laboratory of Respiratory Disease, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, China
Jingxian Huang
Sino-French Hoffmann Institute, State Key Laboratory of Respiratory Disease, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, China
Haoming Li
Sino-French Hoffmann Institute, State Key Laboratory of Respiratory Disease, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, China
Xiaoqing Lin
Sino-French Hoffmann Institute, State Key Laboratory of Respiratory Disease, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, China
Long Tan
Sino-French Hoffmann Institute, State Key Laboratory of Respiratory Disease, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, China
Di Chen
Sino-French Hoffmann Institute, State Key Laboratory of Respiratory Disease, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, China
Xiaohan Zhang
Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
Xiuqing Zhang
Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
Carine Meignin
Université de Strasbourg, CNRS UPR9022, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France
Jean-Luc Imler
Sino-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 author
Hua Cai
Sino-French Hoffmann Institute, State Key Laboratory of Respiratory Disease, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, China; Corresponding author
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.
